Methylation biomarker generation and analysis

Abstract

Disclosed are methods to generate biomarkers that can be used for detection of phenotypes in patients. In an example, a method includes obtaining, from a cohort of subjects, a first plurality of samples from healthy subjects and a second plurality of samples from subjects with a phenotype, and generating sequencing data for the samples. The sequencing data may be used to generate a file having a file format (e.g., a.cpg file), and preliminary segmentation may be performed. Biomarker candidates may be generated by applying a model, and the biomarker candidates scored and / or prioritized to obtain biomarkers for a phenotype. The biomarkers may subsequently be used in a panel to detect the phenotype in a subject.

Description

METHYLATION BIOMARKER GENERATION AND ANALYSISCROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefits of U.S. Provisional Application No. 63 / 618,711 filed January 8, 2024, and U.S. Provisional Application No. 63 / 618,719 filed January 8, 2024, the contents of which are hereby incorporated by reference in their entirety.BACKGROUND

[0002] Detection of diseases at earlier stages of progression can substantially improve patient outcome. Generally, less invasive tests for diseases and other conditions tend to be administered more often than more invasive tests, in part due to risk and compliance considerations. Accordingly, improvements in the ability of non-invasive (or minimally- invasive) tests increases the chances that such tests will be more routinely used, and that conditions will be more often detected (and at earlier stages). For example, a test that requires a blood draw or cheek swab is generally less risky for patients than procedures that require a surgical procedure (e.g., a biopsy), and such a test would thus generally be preferable for patients and clinicians. However, physiological manifestations of a condition might be subtle, especially at earlier stages of a disease, making them more difficult to detect using samples obtained through less-invasive means.

[0003] One way to identify disease indicators that can be used to detect conditions is by analyzing biological data to find informative patterns in the data. But generating, storing, and processing such data is immensely demanding in terms of processing time, storage space, and data transfer requirements. For example, the size of a binary alignment map (BAM) file generated from whole genome sequencing (WGS) of a three billion base pair human genome, with a mean depth of 30x, can be about 100 gigabytes (GB), and analyses can take days if not weeks. Identifying patterns in the data that can lead to new ways of detecting conditions (e.g., by inferring that a patient has a condition based on the findings of a test at the molecular level)can require exponentially more resources, making such processes prohibitively computationally intensive.SUMMARY OF THE DISCLOSURE

[0004] In some aspects, the disclosed approach involves determining a set of features which robustly differentiate diseased samples from healthy or non-diseased samples. Determining the set of features may comprise identifying sets of methylation biomarkers. In example embodiments, these biomarkers are selected from genomic regions containing multiple potentially differentially methylated sites, termed methylation haplotype blocks (MHBs), such as potentially differentially or variably methylated CpG loci. As used herein, CpG loci are regions of deoxyribonucleic acid (DNA) in which a cytosine nucleotide is linearly followed by a guanine nucleotide in the 5' — > 3' direction. Read-level information can be leveraged to identify regions in which patterns of co-methylation are consistently and significantly different between diseased and healthy or non-diseased samples. For example, read-level methylation information can be used to jointly model the methylation status of different CpGs in each genomic window. Various embodiments generate a set of biomarkers which can be used to detect or determine a likelihood of a disease or other condition. These biomarkers can also be used to locate the anatomic site of the disease. Subsets of biomarkers can be selected to be used with samples of patients of different ages, genders, ethnicities, genetic predispositions, comorbidities, clinical manifestations, etc.

[0005] In various embodiments, computational modules are provided for in-depth characterization of genomic regions with methylated cytosines (e.g., CpG di-nucleotides) for appropriate marker selection. For example, tools are provided for full characterization of genomic regions with respect to CpG methylation and potential as methylation biomarker (MBM). Example tools specifically address the needs for efficient manipulation of a large set of whole genome methylome sequencing data, focusing the biomarker discovery search space to relevant parts of the genome, ranking candidate marker regions based on a comprehensive knowledge-base of their characteristics. In various embodiments, a module is configured to preselect potentially informative regions of the genome for downstream analysis. This may involve, for example, using available data to identify methylation cluster regions with high CpG density and co-high methylation, followed by genome segmentation to find MHBs for consideration in methylation biomarker selection.

[0006] In one aspect, various embodiments relate to a method comprising: obtaining, from a cohort of subjects, a first plurality of samples from subjects having a phenotype and a second plurality of samples from subjects without the phenotype; generating a first set of sequencing data for the first plurality of samples and a second set of sequencing data for the second plurality of samples; constructing, using the first set of sequencing data, the second set of sequencing data, or a combination thereof, one or more sequencing files; preliminarily segmenting data in the one or more sequencing files to obtain one or more sets of preliminary DNA segments; and generating, for subsequent use in developing one or more tools for detecting the phenotype in a subject, a set of candidate methylation biomarkers for the phenotype, the generating the set of candidate methylation biomarkers comprising applying a model to the one or more sets of preliminary DNA segments.

[0007] In various embodiments, generating the first and second sets of sequencing data comprises performing methylation sequencing of DNA in the first and second pluralities of samples, respectively. In various embodiments, the first plurality of samples are cell-free DNA (cfDNA) samples and the second plurality of samples are tissue samples. In various embodiments, the one or more files are generated based on one or more Binary Alignment Map (BAM) files and / or Sequence Alignment Map (SAM) files. In various embodiments, constructing the one or more sequencing files comprises generating one or more files in which each line corresponds to a DNA fragment. In various embodiments, for each DNA fragment, the one or more files identify a chromosome and start and end coordinates. In various embodiments, for each DNA fragment, the one or more files identify a methylation pattern. In various embodiments, for each DNA fragment, the one or more files identify a methylation score. In various embodiments, for each DNA fragment, the one or more files identify at least one coordinate corresponding to one or more methylation sites. In various embodiments,preliminarily segmenting the data in the one or more sequencing files comprises constructing a set of preliminary segments based at least on a reference methylome. In various embodiments, preliminarily segmenting the data in the one or more sequencing files comprises constructing a set of preliminary segments based at least on a set of individual methylomes from one or more samples from the cohort of subjects. In various embodiments, preliminarily segmenting the data in the one or more sequencing files is based on one or more criteria. In various embodiments, the one or more criteria comprises a primer length threshold for primer length. In various embodiments, the primer length threshold is between 75 bp and 150 bp. In various embodiments, the one or more criteria comprises a probe length threshold for probe length. In various embodiments, the probe length threshold is between 75 bp and 150 bp. In various embodiments, the one or more criteria comprises a fragment length threshold based on expected fragment lengths. In various embodiments, the fragment length threshold is between 50 to 1200 bp, between 70 to 800 bp, between 100 to 200 bp, between 130 to 180 bp, between 50 to 200 bp, between 60 and 200 bp, between 60 and 150 bp, or between 60 and 100 bp. In some embodiments, the fragment length threshold ranges from 100 to 200 bp, from 120 to 180 bp, from 140 to 160 bp, from 150 to 170 bp, from 160 to 190 bp, or from 170 to 220 bp. In some embodiments, the fragment length threshold is at or less than 500, 400, 200, 150, 100, 90, 75, 70, 60, or 50 bp in length. In various embodiments, the one or more criteria comprises a processivity threshold for the DNA (cytosine-5)-methyltransferase 1 (DNMT1) enzyme. In various embodiments, the processivity threshold is at least between 20 bp and 1000 bp. In various embodiments, the one or more criteria comprises a maximum allowable distance between adjacent CpG loci. In various embodiments, the maximum allowable distance is 150 bp. In various embodiments, preliminarily segmenting the data comprises removing one or more CpGs that are found in less than a threshold percentage of total samples. In various embodiments, the threshold percentage is between about 15% and about 35%. In various embodiments, preliminarily segmenting the data comprises filtering CpG ridges to contain at least a threshold number of CpG sites. In various embodiments, the threshold number is at least 3 CpG sites.

[0008] In various embodiments, preliminarily segmenting the data comprises filtering ridges to have a CpG density of at least a density threshold. In various embodiments, the density threshold is at least 0.02 CpG / bp. In various embodiments, preliminarily segmenting the data comprises filtering ridges (i) to autosomes only, (ii) to having at least 5 CpG sites, and (iii) to having a density of at least 0.03 CpG / bp. In various embodiments, generating the set of candidate methylation biomarkers for the phenotype comprises further segmenting the data. In various embodiments, the model is a Bayesian model. In various embodiments, the model is used to infer and / or estimate change points, which indicate boundaries of regions where a methylation load signal has a variation below a threshold in a given region across all samples within the cohort. In various embodiments, the model fits a piecewise constant function to beta- binomially distributed methylation load signals. In various embodiments, the model employs stochastic variational inference (SVI). In various embodiments, further comprising generating a select set of methylation biomarkers from the set of candidate methylation biomarkers. In various embodiments, generating the select set of methylation biomarkers comprises scoring the methylation biomarkers in the set of candidate methylation biomarkers. In various embodiments, candidate biomarkers are scored based on a signal-to-noise ratio (SNR) so as to prioritize regions where background noise is minimal compared to phenotype signal. In various embodiments, generating the select set of methylation biomarkers comprises prioritizing candidate methylation biomarkers based on one or more criteria. In various embodiments, the one or more criteria comprises designability of probes for the biomarkers. In various embodiments, methylation biomarkers in repeat or low-complexity regions are deprioritized. In various embodiments, further comprising prioritizing the methylation biomarkers for predictive powers across subpopulations. In various embodiments, the select set of methylation biomarkers is a first select set, and wherein the method further comprises generating a second select set of methylation biomarkers. In various embodiments, the first select set of methylation biomarkers corresponds to a first disease subtype and the second select set of methylation biomarkers corresponds to a second disease subtype. In various embodiments, the first select set of methylation biomarkers corresponds to a first population and the second select set of methylation biomarkers corresponds to a second population. In various embodiments, the first select set of methylation biomarkerscorresponds to a first gender and the second select set of methylation biomarkers corresponds to a second gender. In various embodiments, the first select set of methylation biomarkers corresponds to a first ethnicity and the second select set of methylation biomarkers corresponds to a second ethnicity. In various embodiments, the first select set of methylation biomarkers corresponds to a first disease subtype and the second select set of methylation biomarkers corresponds to a second disease subtype.

[0009] In another aspect, various embodiments relate to a method comprising: obtaining a first plurality of samples from subjects with a phenotype and a second plurality of samples from subjects without the phenotype; generating methylation sequencing data for the first plurality of samples and the second plurality of samples; constructing, based on the generated methylation sequencing data, one or more sequencing files; preliminarily segmenting data in the one or more sequencing files to obtain a set of preliminary DNA segments; further segmenting the set of preliminary DNA segments to generate candidate methylation biomarkers; and generating, for subsequent use in developing one or more tools for detecting the phenotype in a subject, a select set of methylation biomarkers from the candidate methylation biomarkers.

[0010] In another aspect, various embodiments relate to a method comprising: generating a first set of methylation sequencing data for a first plurality of samples from subjects with a phenotype and a second set of methylation sequencing data for a second plurality of samples from subjects without the phenotype; constructing, using the first set of methylation sequencing data, the second set of methylation sequencing data, or a combination thereof, one or more sequencing files; preliminarily segmenting data in the one or more sequencing files to obtain one or more sets of preliminary DNA segments; generating a set of candidate biomarkers for the phenotype, the generating the set of candidate biomarkers comprising applying a model to the one or more sets of preliminary DNA segments; and generating a select set of biomarkers from the set of candidate biomarkers for subsequent detection of the phenotype in one or more subjects.

[0011] In another aspect, various embodiments relate to a method for developing, for detection of the phenotype in a subject, a panel based on the set of candidate methylation biomarkers generated by any of the above methods.

[0012] In another aspect, various embodiments relate to a method of detecting a phenotype in a subject using a panel developed based on a select set of methylation biomarkers generated by any of the above methods.

[0013] In another aspect, various embodiments relate to a panel for detecting a phenotype in a subject, the panel being based on a select set of methylation biomarkers generated by any of the above methods.

[0014] In another aspect, various embodiments relate to a method of detecting colorectal cancer in a subject using a panel developed based on a select set of methylation biomarkers generated by any of the above methods.

[0015] In another aspect, various embodiments relate to a panel for detecting colorectal cancer in a subject, the panel being based on a select set of methylation biomarkers generated by any of the above methods.

[0016] In another aspect, various embodiments relate to a computing system comprising one or more processors configured to perform any of the above methods.BRIEF DESCRIPTION OF THE DRAWINGS

[0017] FIG. 1 depicts an overall system that includes a computing system that may interface with other components to enable various aspects of the disclosed approach, according to various embodiments.

[0018] FIG. 2 depicts an example process for generating biomarkers, according to various embodiments.

[0019] FIG. 3A depicts an example workflow, according to various embodiments. FIG. 3B depicts cohort characteristics, with a histogram of age distribution among healthy individuals and CRC patients (left), self-reported ethnicity among healthy individuals and CRC patients (middle), and proportion of CRC patients by stage of disease progression, further stratified by micro satellite status (right), according to various embodiments.

[0020] FIG. 4 provides cohort level distributions of coverage, methylation level, and protection rate, according to various embodiments.

[0021] FIG. 5 provides a cohort CpG coverage plot, according to various embodiments. The number of CpGs covered is plotted against the fraction of samples in each group covering those CpGs.

[0022] FIG. 6 provides length (left panel), number of CpG sites (middle panel), and density distribution (right panel) of the filtered ridge set, according to various embodiments. Red line shows the median, and shaded region is the interquartile range (IQR).

[0023] FIG. 7 depicts a comparison of different baselines from the literature, according to various embodiments.

[0024] FIG. 8 illustrates an example CpGBlocks latent variable model of processive methylation of CpG sites by DNA (cytosine-5)-methyltransferase I (DNMT1), according to various embodiments.

[0025] FIG. 9 includes plots of some of the regions differentially methylated between healthy (blue) and CRC (red) cohorts identified using a machine learning model developed to discover differentially-methylated regions between healthy and disease cohorts as well as between subpopulations within the disease cohort, including age, sex, stage, histology, and MSI vs microsatellite stability (MSS), according to various embodiments. The plots illustrate a segmentation procedure using the machine learning model. For a region, FIG. 9 plots the methylation load of the healthy cohort and tumor cohort and demonstrates the segmentationprocedure and scoring / ranking. The horizontal bars in the lower panel show the differential methylation load.

[0026] FIG. 10 depicts differential methylation load and CpG density distribution of biomarker candidates, according to various embodiments, colored by their differential methylation status: hyper-methylated, hypo-methylated, and not significantly differentially methylated according to a Wald test of significance.

[0027] FIG. 11 depicts number of biomarkers and the differential methylation score cutoff based on a preset 2Mbp total panel size (left) and CpG density, length and methylation load distribution of biomarker candidates (right), according to various embodiments.

[0028] FIGs. 12A and 12B depict extracting fragment information and combining CpG methylation status of two paired reads, with 12A illustrating overlapping reads and 12B illustrating non-overlapping reads, according to various embodiments.

[0029] FIG. 13 provides an example of a CpG file (referred to interchangeably as “cpg file” or “.cpg file”) containing fragments mapped to a segment of a chromosome, according to various embodiments.

[0030] FIG. 14 depicts an expanded methylation pattern in an example CpG file, according to various embodiments.

[0031] FIG. 15 illustrates “CpGReads,” showing extended CpG status of reads in a genomic window from the CpGReads module, according to various embodiments.

[0032] FIG. 16 illustrates CpGReads and compact CpG block visualization along with inferred methylation states, according to various embodiments.

[0033] FIG. 17 depicts population level plots of CpG matrices, according to various embodiments, in which “H” corresponds to “healthy” subjects in a cohort and “D” corresponds to “disease” subjects in the cohort.

[0034] FIG. 18 depicts a triangle heatmap showing pairwise correlation of methylation levels between CpGs, according to various embodiments. CpG coordinates are listed in genomic order on the right, and positions of interest are highlighted in red. The bars correspond to fraction methylated or beta-value for each CpG in this region of interest.

[0035] FIG. 19 depicts triangle heat maps plotted according to various embodiments. Both regions are hyper-methylated in CRC samples (left column) compared to healthy samples (right column) as depicted by the gray bars. However, the level of co-methylation is different between the two targets, which can be used as a way of ranking genomic regions for marker selection.

[0036] FIG. 20 depicts overall findings of an example analysis according to various embodiments. Red line shows the median, and the shaded region is the interquartile range (1QR). In total, 184,265 differentially methylated regions between healthy and CRC cohorts were identified, spanning more than 1.71 million CpGs and more than 18.76 Mbp. 76% of all identified regions were hypermethylated (70% CpG islands, 1.3% CpG shelves, 21% CpG shores) and the rest were hypomethylated (7.3% CpG islands, 8.6% CpG shelves, 25% CpG shores). Out of which, 11,579 biomarkers spanning 1.69Mbp were selected for the final panel based on various filters and criteria.

[0037] FIG. 21 depicts a subpopulation analysis according to various embodiments, with the right panel representing micro satellite status and the left panel representing mucinous adenocarcinoma. Red line shows the median, and shaded region is the interquartile range (IQR). 220 hypermethylated regions were differentially methylated between CRC MSI samples and CRC MSS samples and healthy cfDNA samples. Subtype-specific differentially methylated regions, such as 62 hyper- methylated regions that were differentially methylated between mucinous adenocarcinoma samples and the rest of the cohort, were identified.

[0038] FIG. 22 depicts a block diagram of a representative server system and client computer system usable to implement various embodiments of the present disclosure.DETAILED DESCRIPTION[00391 Epigenetic alterations have been shown to govern many phenotype or disease states, including cancer. A key epigenetic marker in humans is the DNA methylation of CpGs. DNA methylation is fundamental to gene regulation and cell identity. DNA methylation (e.g., patterns of CpG methylation) can directly alter gene regulation and cell identity through alteration of chromatin accessibility. Methylation can be positively or negatively associated with transcription factor binding events, which in turn alter the cell’s transcription programs.

[0040] Aberrations in patterns of DNA methylation (e.g., aberrations in patterns of comethylation of adjacent CpG loci) are an indicator of a certain phenotype, including for example a disease, disease type, and / or disease progression. In the case of cancer, for example, aberrations are associated with different aspects of cancer, from tumor initiation to cancer progression and metastasis. For example, between 0.2% to 80% of the genome may be differentially methylated in cancers, and methylation thus is uniquely suited both for cancer detection and for tissue of origin (TOO) prediction. Differentially methylated regions are ideal biomarkers for early cancer detection due to their frequency and homogeneity across patients and subpopulations of patients. Likewise, differences in methylation patterns between maternal and fetal DNA, for example, can be used in various non-invasive prenatal testing applications. In addition, cell-specific methylation changes can be used to detect, monitor, or predict transplant rejection.

[0041] Methylation status of CpG loci in a genomic region proves to be spatially correlated, giving rise to a host of methods that leverage this pattern to increase the effective signal-to-noise ratio (SNR) in determining cell-type of origin and early diagnostics (e.g., cancer diagnostics), especially considering the limited depth of whole genome bisulfite sequencing (WGBS) datasets. WGBS is a next-generation sequencing technology used to determine DNA methylation status of single cytosines, and involves treating DNA with sodium bisulfite before high-throughput DNA sequencing. The treatment with sodium bisulfite converts unmcthylatcd cytosines into uracil, enabling methylation detection by helping distinguish methylated cytosines,which resist bisulfite treatment, from uracil. Other deamination agents (e.g. APOBEC) or reducing agents (e.g. borane), alone or in combination with an oxidizing agent (e.g. TET, potassium ruthenate) and / or a glycosylation agent (e.g. T4 P-glucosyltransferase), that specifically discriminate between methylated and unmethylated cytosines and / or different forms of methylated cytosines may also be used. During polymerase chain reaction (PCR) amplification, the uracils or dihydrouridines are converted into thymines, and unconverted cytosine forms are recognized as cytosines. Locations of methylated cytosines can be identified by comparison of, for example, a bisulfite-treated DNA sequence with an original DNA sequence. Non-conversion based methylation detection methods (e.g. MSRE / MDRE, MBD, McDIP, or direct detection by long read sequencers) may also be used.

[0042] High local methylation correlation means that multiple CpGs can be integrated into methylation haplotypes which strongly increase SNR, in particular at low circulating tumor DNA (ctDNA) fractions. The rationale for methylation haplotypes is similar to phased singlenucleotide variants (SNVs), with the difference that sequencing errors for bisulfite sequencing are approximately two orders of magnitude higher (due to conversion and protection errors), and hence it becomes useful to leverage adjacent CpGs.

[0043] Concordant hypo-methylation of consecutive CpG loci within large genomic regions has been used in cancer diagnosis and is associated with cancer initiation and chromatin and genomic instability. Similarly, hyper-methylation of CpG loci in the promoter region of tumor suppressor genes occurs in tumor cells which is associated with gene suppression and tumor cell proliferation. These observations support the idea of considering concomitant changes in CpG methylation patterns over an entire genomic region as a single biomarker in cancer diagnosis and cell-type of origin problems.

[0044] Differentially methylated regions (DMRs) are genomic regions, typically with multiple adjacent CpG sites, that have different DNA methylation status among different biological samples, such as different cclls / tissucs within the same individual, the same ccll / tissucat different times, different cells / tissues from different individuals, or different alleles in the same cell.

[0045] In some embodiments, differentially methylated genomic patterns are defined between patients with colorectal cancer (CRC) and healthy or non-CRC individuals by utilizing patterns of co-methylation of adjacent CpG loci. Example embodiments seek to identify and characterize CRC and advanced adenomas (AA) that can develop into CRC through CRC / AA- specific MBM via identification of tumor-specific differentially methylated regions from a large set of wide genomic regions, further discussed below. To achieve a set of features which robustly differentiate tumor from healthy or non-diseased samples, example embodiments use read-level methylation information to jointly model the methylation status of different CpGs in each genomic window. Joint modeling of methylation patterns of consecutive CpG loci leverages read-level information, which has the statistical power to distinguish between, for example, tumor-derived DNA and normal fragments even in presence of rare amounts of tumor fraction in low-coverage. Modeling helps identify new biomarkers that can be used in panels with target- specific primers or probes that increase detection sensitivity and specificity for cancer or other diseases. The disclosed approach can provide a set of biomarkers which can be used to detect a phenotype or a disease (in example embodiments, CRC and AA), and which can be subselected to be used with patients of different ages, genders, ethnicities, genetic predispositions, comorbidities, clinical manifestations etc. The methods disclosed herein can also be used to identify and characterize biomarkers suitable for detecting other cancers or phenotypes, or for differentiating cancer types, origins, or states.

[0046] To identify tightly co-methylated blocks across the genome, various embodiments preliminarily segment the whole genome into smaller regions based on biological priors and the sequencing technology and a chosen processing pipeline before any further analysis or modeling of the data. There are at least several main benefits to this preliminary segmentation. First, the preliminary segmentation drastically reduces the computational complexity, which in turn results in reduced computational cost and time. Second, the preliminary segmentation guides the biomarker discovery towards more valid segments which satisfy the biological and sequencingtechnology priors. Third, the preliminary segmentation reduces the number of probes or primers needed to cover the designed panel by removing parts of the genome which are less informative.

[0047] In example embodiments, the preliminary segmentation can be based on certain selected criteria. For example, as a first criterion, the preliminary segmentation can employ a threshold based on a certain primer or probe length, such as 75 bp to 150 bp (e.g., about 75 bp, about 80 bp, about 85 bp, about 90 bp, about 95 bp, about 100 bp, about 105 bp, about 110 bp, about 115 bp, about 120 bp, about 125 bp, about 130 bp, about 135 bp, about 140 bp, about 145 bp, or about 150 bp). As a second criterion, the preliminary segmentation can employ a threshold based on expected fragment lengths, such as between 60 bp to 140 bp (e.g., about 60 bp, about 65 bp, about 70 bp, about 75 bp, about 80 bp, about 85 bp, about 90 bp, about 95 bp, about 100 bp, about 105 bp, about 110 bp, about 115 bp, about 120 bp, about 125 bp, about 130 bp, about 135 bp, or about 140 bp). As a third criterion, the processivity (in bp) of the DNA (cytosine-5)-methyltransferase 1 (DNMT1) enzyme may be set from tens of base pairs to a few hundred base pairs.

[0048] In various embodiments, probabilistic modeling, such as hierarchical Bayesian modeling (e.g., fully variational Bayesian modeling), is used to further segment and define a narrower set of relevant genomic regions, such as DMRs that can potentially be used as biomarkers for disease or phenotype detection. In various embodiments, a hierarchical Bayesian model is designed and implemented to infer and estimate change points, which indicate the boundaries of regions where the methylation load signal is relatively constant or almost constant in a given region across all samples within a cohort. In various embodiments, hierarchical Bayesian modeling is used to fit a piecewise constant function to beta-binomially distributed methylation load signals. The modeling takes into consideration not only the beta (expected) values of the signals but also the variance of the beta values. In some embodiments, stochastic variational inference (SVI) is used. The variational probabilistic modeling methods disclosed herein have several advantages. For example, a generative model can be trained as close as possible to the biological explanations of the CpG methylation patterns. Publicly available information can be leveraged to construct priors, which can be injected at different levels of themodel. Hypothesis testing can be performed very naturally as these models can be fully investigated. The probability distribution of the unknown parameters (such as CpG loci methylation status) can be inferred, informed by uncertainty estimation. Once the probability distributions are inferred, the probability of two distributions being different can be easily estimated. In various embodiments, the disclosed approach improves and expands on prior approaches at least by: (i) considering each read’s mapping quality in joint modeling of CpG loci; (ii) inferring the methylation state of a tentative biomarker through modeling of the processivity of DNMT1 via jointly modeling adjacent CpG loci methylation patterns; and (iii) benchmarking different models of varying complexity.

[0049] In various embodiments, after regions where the methylation status is relatively constant or almost constant across all samples within a cohort are identified, regions where the methylation status are significantly different between samples from different cohorts are identified as biomarker candidates, and the identified regions are scored and / or prioritized based on their respective association with different clinical covariates to obtain a select set of the biomarker candidates for clinical use.

[0050] Sample Extraction and Enrichment of DNA Molecules

[0051] Samples that are useful for methods herein can be virtually any nucleic acid sample. In illustrative embodiments, the nucleic acid sample is extracted or isolated from a subject or a population of subjects. In illustrative examples, DNA molecules are extracted or isolated from a sample such as a tissue sample (e.g., fresh-frozen tissue, FFPE tissue) or a liquid sample (e.g., blood, plasma, serum, urine, vitreous, sputum, saliva, tears, perspiration, ascites fluid, feces, bile, lymph, cervical mucus, semen).

[0052] DNA methylation biomarkers are increasingly being utilized in the development of novel assays for use in, for example, cancer and other disease detection, women’s health, organ health, and veterinary health. For example, methylation profiling is being used in non- invasive prenatal testing (NIPT) for monitoring of placental and fetal epigenomic changes, pre-symptomatic detection of preterm birth, preeclampsia, placental insufficiency, and fetal growth restriction. Methylation markers can also be indicative of congenital diseases of the fetus. Furthermore, methylation biomarkers are also used for monitoring of organ health such as predicting and monitoring organ rejection in transplant patients, monitoring of immune changes in transplant rejection, and for monitoring of organ health in high risk or predisposed individuals. In addition, methylation biomarkers can be used to determine biological age or detect age-related diseases. Accordingly, the sample described herein may be a maternal sample, a fetal sample, a sample from a transplant patient, or a sample from a subject having, had, suspected of having, or at risk of having a certain phenotype or a certain disease (e.g., cancer).

[0053] In certain illustrative embodiments, isolation of cfDNA from a liquid (e.g., blood or blood derivative sample such as a serum or plasma sample) can involve binding DNA molecules from a sample to a matrix and isolating the DNA molecules in the presence of a solvent. In some embodiments, the method further comprises incubating the biological sample comprising DNA molecules with a protease, prior to contacting the DNA molecules to the matrix. In some embodiments, the method can further include the steps of washing the matrix with a wash buffer to remove impurities, and optionally, drying the matrix. Enriched nucleic acid samples can be eluted from the matrix with an elution buffer.

[0054] Other methods for nucleic acid isolation, for example cfDNA isolation, and optional enrichment of certain cfDNA can include ion exchange columns, or microfluidic devices, such as solid phase isolation, based on DNA capture by immobilized beads or functionalized surface. Additional methods include liquid phase isolation, utilizing an electric field, or chemical reagents, instead of a functionalized surface. In illustrative embodiments herein, isolation of cfDNA from a patient sample is performed using a DNA isolation kit (e.g., QIAamp Circulating Nucleic Acid kit (Qiagen)).

[0055] Library Preparation

[0056] In some embodiments, the method further comprises fragmenting the extracted DNA or derivative thereof. In some embodiments, the method further comprises appending adaptors to the extracted DNA or derivative thereof. In some embodiments, the adaptors are Y- adaptors. In some embodiments, the adaptors comprise a universal priming site, a molecular barcode, and / or methylated cytosines.

[0057] Typically, methods herein include a step of appending nucleic acid adaptors to extracted DNA molecules or to nucleic acid derivatives generated therefrom. For example, adaptors may be appended on to the DNA molecules by ligation. The extracted DNA molecules in illustrative embodiments are extracted from a sample of a subject. In some embodiments, appending nucleic acid adaptors is preformed after the extracted DNA molecules are fragmented to form fragmented DNA molecules. Typically, methods include exposing the extracted DNA molecules to one or more polymerases or kinases, such as Klenow Large Fragment Polymerase and T4 polynucleotide kinase (PNK), as well as a ligase, such as T4 ligase. In some embodiments, the extracted DNA molecules or the fragmented DNA molecules are exposed to one or more polymerases and / or kinases to generate the nucleic acid derivatives. In some embodiments, the method further comprises appending adaptors to the nucleic acid derivatives generated therefrom. In some embodiments, the extracted DNA molecules are not fragmented prior to appending nucleic acid adaptors thereto. In some embodiments, the extracted DNA molecules are cellular DNA molecules extracted from a tissue sample (e.g., fresh-frozen tissue, FFPE tissue). In some embodiments, the extracted DNA molecules are cfDNA molecules.

[0058] In some embodiments, adaptors are ligated to the extracted DNA molecules. Before such ligation, the extracted DNA molecules can be modified to form sample nucleic acid derivatives, for example to make them more amenable to adaptor ligation. For example, extracted DNA molecules can be blunt ended, nucleotides can be added to the extracted DNA molecules or blunted-ended derivative therefrom, and / or phosphate moieties can be added or removed from the ends of sample DNA molecules or derivatives thereof. In some embodiments, prior to ligation, the extracted DNA molecules may be blunt ended, and then a single adenosine base can be added to the 3’ end. Prior to ligation the DNA may be cleaved using a restrictionenzyme or some other cleavage method. During ligation the 3’ adenosine of the DNA fragments and the complementary 3’ thymidine overhang of an adaptor can enhance ligation efficiency. In some embodiments, adaptor ligation is performed using a T4 ligase.

[0059] In some embodiments, adaptors containing one or more universal priming sequences are utilized in methods herein. In some embodiments, the adaptors are Y adaptors, for example in methods involving NGS sequencing. In some embodiments, the adaptors each comprises a universal priming site. The adaptors may or may not include methylated cytosine residues.

[0060] In some embodiments, the adaptor may comprise a sample barcode. Thus, multiple samples can be analyzed in the same sequencing reaction. The sample barcode can be used to process data according to the sample from which the data was generated.

[0061] In some embodiments, the adaptor may comprise a molecular barcode or molecular index tag (MIT). In some embodiments, the number of adaptors having different MITs is between 10 to 1,000, and wherein the ratio of the total number of template nucleic acid or cfDNA molecules to the number of different MITs in the ligation reaction is at least 1,000:1. The number of different MITs in the ligation reaction, in certain embodiments, ranges fromlO to 50, 10 to 100, 50 to 200, 100 to 300, 200 to 500, 300 to 600, 500 to 700, 600 to 800 or 700 to 1,000. In some embodiments, there are at least 1, 10, 20, 30, 40, 50, or at least 100; 200, 300, 400, 500, 600, 700, 800, 900, or 1000 different MITs in the ligation reaction. In some embodiments, the ratio of the total number of template nucleic acid or cfDNA molecules to the number of different MITs in the ligation reaction is at least 10,000:1. In some embodiments, the ratio of the total number of template nucleic acid or cfDNA molecules to the number of different MITs in the ligation reaction ranges from 50,000: 1 to 50:1, from 25,000: 1 to 100:1, from 10,000:1 to 100:1, from 10:000:1 to 8,000:1 to 500:1, from 5,000:1 to 200:1, from 10,000:1 to 50:1. In some embodiments, the methods disclosed herein result in at least 100; 200; 500; 750; 1,000; 2,000; 5,000; 7,500; 10,000; 20,000; 25,000; 30,000; 40,000; 50,000 different MITs to each one template nucleic acid or cfDNA molecules.

[0062] Treatment to Discriminate between Methylated and Unmethylated Cytosines

[0063] Any method suitable for detecting methylated cytosines at a single-base resolution may be used. In some embodiments, the extracted DNA or derivative thereof is treated with a deaminating agent that converts (directly or indirectly through one or more other agents) unmethylated but not methylated cytosines to uracils. In some embodiments, the deaminating agent (e.g., a chemical reagent such as sodium bisulfite) directly converts unmethylated cytosines to uracils. In some embodiments, the deaminating agent converts unmethylated cytosines to uracils in combination with one or more other agents - for example, in order to convert unmethylated cytosines to uracils, the extracted DNA or derivative thereof may be first treated with an oxidizing agent (e.g., TET or its catalytic domain) that oxidizes one or more forms of methylated cytosines (e.g., 5hmC or 5mC), followed by treatment with a deaminase (e.g., APOBEC or its catalytic domain).

[0064] In some embodiments, the deaminating agent comprises a chemical reagent (e.g., sodium bisulfite). In some embodiments, the deaminating agent comprises a deaminase (e.g., APOBEC) or its catalytic domain. In some embodiments, the deaminating agent comprises APOBEC3A (A3 A) or its catalytic domain.

[0065] In some embodiments, the extracted DNA or derivative thereof is treated with a reducing agent that converts certain forms of modified cytosines, but not unmodified cytosines, into dihydrouridine (DHU). In some embodiments, the reducing agent comprises pyridine borane.

[0066] In some embodiments, the extracted DNA or derivative thereof is treated with an oxidizing agent that oxidizes one or more forms of methylated cytosines before being treated with a deaminating agent or a reducing agent. In some embodiments, the oxidizing agent oxidizes 5hmC and 5mC to 5caC (5 -carboxylcytosine). In some embodiments, the oxidizing agent selectively oxidizes 5hmC, but not 5mC, to 5fC (5-formylcytosine). In some embodiments, the oxidizing agent comprises an enzyme of the ten-eleven translocation (TET) families or itscatalytic domain. In some embodiments, the oxidizing agent comprises TET1 or its catalytic domain. In some embodiments, the oxidizing agent comprises TET2 or its catalytic domain. In some embodiments, the oxidizing agent comprises TET3 or its catalytic domain. In some embodiments, the oxidizing agent comprises potassium perruthenate (KRuCE). In some embodiments, the oxidizing agent comprises potassium ruthenate (K2RUO4).

[0067] In some embodiments, the extracted DNA or derivative thereof is treated with a glycosylation agent that glycosylates 5hmC to glucosyl-5hmC (5ghmC) to protect it from oxidation, deamination, or reduction before being treated with an oxidizing agent, a deaminating agent, or a reducing agent. In some embodiments, the glycosylation agent is a glycosyltransferase. In some embodiments, the glycosyltransferase is a glucosyltransferase. In some embodiments, the glucosyltransferase is P-glucosyltransferase (P-GT). In some embodiments, the glucosyltransferase is P-GT of T4 phase.

[0068] In some embodiments, the extracted DNA or derivative thereof is treated with a methylation sensitive restriction enzyme (MSRE), methylation dependent restriction enzymes (MDRE), a 5 -methylcytosine (5mC) antibody, a 5 -hydroxymethylcytosine (5hmC) antibody, a methyl-CpG-binding domain (MBD) protein, or a DNA methyltransferase. In some embodiments, other methylation detection methods such as methylated DNA immunoprecipitation (MeDIP) or direct detection by long read sequencers may also be used.

[0069] Conversion-based methylation detection

[0070] In some embodiments, the methods described herein include treating the extracted DNA molecules or their derivatives with one or more chemical or enzymatic agents or a combination of chemical and enzymatic agents (e.g. deaminating agents, reducing agents, oxidizing agents, glycosylation agents) that allow discrimination between methylated and unmethylated cytosines, or between 5mC and 5hmC. In some embodiments, a portion of a library of DNA molecules or their derivatives is treated with one or more such chemical and / or enzymatic agents. For example, in some embodiments, 10%, 20%, 30%, 40%, 50%, 60%, 70%,80%, or 90% of the library is treated with one or more such chemical and / or enzymatic agents. In some embodiments, the entire library of DNA molecules or their derivatives is treated with one or more such chemical or enzymatic agents.

[0071] In some embodiments, the agent comprises a deaminating agent. In some embodiments, the deaminating agent comprises an enzyme such as a deaminase or its catalytic domain. In some embodiments, the deaminase may be APOBEC or its catalytic domain. In some embodiments, the deaminase may be APOBEC3A (A3 A) or its catalytic domain, which deaminates unmethylated C, 5mC, and 5hmC, but not 5ghmC, 5fC, or 5caC. In some embodiments, the method described herein involves treating the extracted DNA molecules or their derivatives with TET2 / oxidation enhancer, which converts 5mC and 5hmC to 5caC and protects them from deamination by APOBEC, followed by treatment with APOBEC to deaminate the unmethylated cytosines to uracils. In some embodiments, the DNA sample is treated with a glycosylation agent (e.g. T4 P-glucosyltransferase) to glycosylates 5hmC to 5ghmC and protects it from deamination by APOBEC.

[0072] In some embodiments, the deaminating agent comprises a bisulfite reagent. Bisulfite reagents, such as sodium bisulfite, convert unmethylated cytosine to uracil and leave methylated cytosine (including 5mC and 5hmC) unchanged. Therefore, after bisulfite treatment, 5mC and 5hmC in the DNA remains as cytosine and unmodified or unmethylated cytosine will be changed to uracil. In some embodiments, the bisulfite reagent may be sodium bisulfite, potassium bisulfite, ammonium bisulfite, magnesium bisulfite, sodium metabisulfite, potassium metabisulfite, ammonium metabisulfite, magnesium metabisulfite, and equivalents. In some embodiments, a combination of one or more chemical reagents and / or one or more enzymes can be used to discriminate between various forms methylated cytosines (e.g., mC or hmC) and unmethylated cytosines. For example, in some embodiments, the DNA sample is treated with an oxidizing agent (e.g. KRuCE or K2RUO4) that selectively oxidizes 5hmC, but not 5mC, to 5fC before bisulfite treatment, which converts unmethylated cytosine (including 5fC converted from 5hmC) to uracil but leaving 5mC unchanged. In some embodiments, a glycosylation agent (e.g. T4 P-glucosyltransferase or its catalytic domain) is used to glycosylate 5hmC to 5ghmC and anoxidizing agent (e.g. a TET enzyme or its catalytic domain) is used to convert 5mC to 5caC before bisulfite treatment, which converts unmethylated cytosine (including 5caC converted from 5mC) to uracil but leaving methylated cytosine (including 5ghmC converted from 5hmC) unchanged.

[0073] The bisulfite treatment can be performed by commercial kits such as the Imprint DNA Modification Kit (Sigma), EZ DNA Methylation- DirectTM Kit ( ZYMO), and the EZ DNA Methylation-Gold Kit (ZYMO). After DNA bisulfite conversion, single stranded DNA is captured, desulphonated and cleaned. The bisulfite-treated DNA can be captured by purification columns or magnetic beads and eluted. Bisulfite-treated single stranded DNA can be converted into dsDNA through an enzyme-catalyzed DNA strand synthesis with appropriate primers and polymerase. The polymerase will recognize the uracil in the ssDNA template as thymine and add an adenine to the complimentary strand. Further polymerase extension on the complimentary strand will result in replication of the original bisulfite treated ssDNA template, substituting uracil with thymine. Identification of cytosine to thymine conversion and guanine to adenine conversions (complementary strand) through comparing to the reference genome, will determine all unmodified cytosines, while the remaining cytosines are considered to be methylated.

[0074] In some embodiments, the agent comprises a reducing agent (e.g. pyridine borane) that selectively reduces 5fC and 5caC to dihydrouridine (DHU), which, like uracil, is converted to T base following PCR amplification. In some embodiments, the method described herein involves treating the extracted DNA molecules or their derivatives with TET2 / oxidation enhancer, which converts 5mC and 5hmC to 5caC, followed by treatment with borane, which reduces 5fC and 5caC (including 5caC converted from 5mC and 5hmC) to DHU but leaves unmodified cytosine (dC) unchanged. In some embodiments, the DNA sample is treated with an oxidizing agent (e.g. KRuCE or K2RUO4) that selectively oxidizes 5hmC, but not 5mC, to 5fC, followed by treatment with borane, which reduces 5fC (including 5fC converted from 5hmC) and 5caC to DHU but leaves dC and 5mC unchanged. In some embodiments, the DNA sample is first treated with a glycosylation agent (e.g. T4 P-glucosyltransferase) and an oxidizing agent (e.g. TET) such that 5hmC is glycosylated to 5ghmC and only 5mC is oxidized and converted to5caC. The subsequent treatment with borane reduces 5fC and 5caC (including 5caC converted from 5mC) to DHU but leaves dC and 5ghmC unchanged.

[0075] Other conversion-based methyl detection methods, including EM-seq, oxidative bisulfite sequencing (oxBS-seq), TET-assisted bisulfite sequencing (TAB-seq), TET-assisted pyridine borane sequencing (TAPS), TAPS with T4-0GT protection sequencing (TAPS0), chemical-assisted pyridine borane sequencing (CAPS), and many variants of these that can discriminate between C, mC, and / or hmC. These methods can be performed with commercial kits such as NEBNext® Enzymatic Methyl-seq (EM-seq™) (New England Biolabs, Inc.), the 5hmC TAB-Seq Kit (WiseGene), and the EpiTect® Bisulfite Kit (Qiagen), for example.

[0076] Restriction enzyme-based methylation detection

[0077] In some embodiments, the methods described herein include treating the extracted DNA molecules or their derivatives with one or more restriction enzymes. In some embodiments, the one or more restriction enzymes are one or more methylation sensitive restriction enzymes (MSREs). In some embodiments, a portion of a library of DNA molecules is treated with one or more MSREs. For example, in some embodiments, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the library is treated with one or more MSREs. In some embodiments, the entire library of DNA molecules is treated with one or more MSREs.

[0078] MSREs are useful in analyzing the methylation status of cytosine residues in CpG sites. As the name implies, these enzymes are not able to cleave their palindromic target sites when the cytosine residues are methylated. The size of the MSRE targets sites range from 4 bp up to 76bp, but typically are in the 4 to 8 bp range.

[0079] In one aspect, methods herein typically include contacting the extracted DNA molecules or their derivatives with one or more MSREs. MSREs selectively cleave a sample nucleic acid when the MSRE recognition site is unmethylated, but not when the MSRE recognition site is methylated. An “isoschizomer” of an MSRE is a restriction enzyme that recognizes the same recognition site as a methylation sensitive restriction enzyme but cleavesboth methylated CGs and unmethylated CGs. Isoschizomer of the selected MSREs may be used in control reactions. Non-limiting examples of methylation sensitive restriction enzyme include, and thus in some embodiments, the one or more MSREs can include, Aatll, Acc65I, AccI, Acil, Acll, Afel, Agel, Agel-HF®, AhdI, Alel-v2, Apal, ApaLI ApeKI, Asci, AsiSI, Aval, Avail, Bael, BanI, BbvCI, BceAI,, Bcgl, BcoDI, BfuAI, Bgll, BmgBI, BsaAI, BsaBI, BsaHI, Bsal- HF®v2, BseYI, BsiE, BsiWI, BsiWI-HF®, BslI, BsmAI, BsmBI-v2, BsmFI, BspDI, BspEI, BsrBI, BsrFI-v2, BssHII, BstAPI, BstBI, BstUI, BstZ17I-HF®, BtgZI, Cac8I, Clal, Dpnl, Dralll-HF®, DrdI, Eael, Eagl-HF®, Earl, Ecil, Eco53kl, EcoRI, EcoRI-HF®, EcoRV, EcoRV- HF®, Esp3I, Faul, Fnu4HI, FokI, Fsel, FspI, Haell, Hgal, Hhal, HinPlI, Hindi, Hinfl, Hpal, Hpall, Hpyl66II, Hpyl88III, Hpy99I, HpyAV, HpyCH4IV, KasI, Mbol, Mlul, MluI-HF®, Mmel, MspAlI, Mwol, Nad, Narl, Neil, NgoMIV, Nhd-HF®, NlalV, Notl, Notl-HF®, Nrul, NruI-HF®, Nt. BbvCI, Nt.BsmAI, Nt.CviPII, PaeR7I, PaqCI, Pld, PluTI, Pmd, Pmll, PshAI, PspOMI, PspXI, Pvul, PvuI-HF®, Rsal, RsrII, SacI-HF®, SacII, Sall, Sall-HF®, Sau3AI, Sau96I, ScrFI, SfaNI, Sfil, Sfol, SgrAI, Smal, SnaBI, Srfl, StyD4I, Tfil, Tsd, TspMI, Xhol, Xmal, and / or Zral. In illustrative embodiments, the one or more MSREs can include Hhal, Hpall, BstUI, and / or HpyCH4IV.

[0080] In some embodiments, the one or more restriction enzymes are one or more methylation dependent restriction enzymes (MDREs). MDREs selectively cleave a sample nucleic acid when one or more nucleotides in the MDRE recognition site is methylated. In some embodiments, one or more MDREs can be used in combination with one or more MSREs. In some embodiments, the one or more MDREs can be AbaSI, AoxI, BisI, BlsI, Dpnl, FspEI, Glal, Glul, Krol, LpnPI, Mall, MspJI, Mtd, Pcsl, PkrI, or Sgd.

[0081] The MSRE or MDRE can be selected based on differentially methylated CpG sites in target DNA molecules, such as tumors or ctDNA from specific cancer targets, or a diverse spectrum of tumors. Further criteria for selection may include low background methylation in normal tissues, size and number of cleavage fragments, number of base pairs of recognition sequence, whether the cleavage results in blunt vs. tailed end fragments, and whetherthe enzymes have the same or similar reaction conditions such that the contacting step can be done under the same set of conditions and / or in a single reaction.

[0082] In some embodiments, more than one, a plurality, or a set of MSREs (and / or MDREs) can be used to contact the extracted DNA molecules or their derivatives. The number of selected MSREs in certain embodiments is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 20, 25, 50 or 100. In some embodiments, the number of MSREs range from 1 to 2, 3, 4, 5, 6, 7, 8, 9, 10, or 20, 25, 50 or 100; from 2 to 3, 4, 5, 6, 7, 8, 9, 10, or 20, 25, 50 or 100; or from 5 to 6, 7, 8, 9, 10, or 20, 25, 50 or 100. In some embodiments, the number of MSREs range from 1 to 10, 1 to 5, from 2 to 5, from 3 to 5, from 4 to 5, 3 to 7, from 5 to 10, from 6 to 10, or from 7 to 10. Thus, criteria such as target site, target site methylation status, number of base pairs in tailed end fragments, reaction conditions including but not limited to buffer conditions, incubation time and temperature for optimal activity, as well as deactivation time and temperature for each MSRE can be used for selecting the plurality or set of MSREs and / or MDREs to include in the method. As activity measured by units is specific to each enzyme, the target DNA molecules can be contacted with from 1 to 5 Units (U) of each MSREs in the reaction sample. In some embodiments, the extracted DNA molecules or their derivatives are contacted with from 1 to 5 U, from 1.5 to 4 U, from 2 to 3 U, from 2.5 to 4 U, or from 3 to 5 U of each MSRE. In some embodiments, one or more of the MSRE is selected from Hpall, Sall, Bbel, Notl, Smal, Xmal, Mbol, BstUI, BstBI, Clal, Mlul, Nael, Narl, Pvul, Sadi, HpyCH41V, Hhal, and combinations thereof. In exemplary embodiments, the one or more MSREs is selected from one or more of Hpall, Hhal, HpyCH41V, and BstUI. In some embodiments, the one or more MSREs are selected from one or more of Hpall, Hhal, HpyCH41V, or BstUI. In some embodiments of the methods as described herein, the contacting comprises contacting with two or more MSREs. In some embodiments, the contacting comprises contacting with three or more MSREs. In some embodiments, the contacting comprises contacting with four or more MSREs. In some embodiments, the contacting comprises contacting with the two or more MSREs in a single reaction.

[0083] In some embodiments, MSREs and / or MDREs are included that are able to cleave the MSRE sites and / or MDRE sites in the same cleavage buffer conditions. In some embodiments, the cleavage buffer conditions include 5-500 mM potassium acetate, for example 25-100 mM potassium acetate. In some embodiments, the cleavage buffer conditions include 2- 200 mM Tris-acetate, for example 10-40 mM Tris-acetate. In some embodiments, the cleavage buffer conditions include 1-100 mM magnesium acetate, for example 5-20 mM magnesium acetate. In some embodiments, the cleavage buffer conditions include 10-1000 pg / ml recombinant albumin, for example 50-200 pg / ml recombinant albumin. In some embodiments, the pH is between 6.9 and 8.9 at 25 °C, for example, between 7.4 and 8.4, 7.5 and 8.3, 7.6 and 8.2, 7.7 and 8.1, or 7.8 and 8, or about 7.9 at 25 °C. In some embodiments, the cleavage buffer conditions include 1-100 mM bis-tris-propane-HCl, for example 5-20 mM bis-tris-propane-HCl. In some embodiments, the cleavage buffer conditions include 1-100 mM MgC12, for example 5- 20 mM MgC12. In some embodiments, the pH is between 6 and 8 at 25 °C, for example, between 6.5 and 7.5, 6.6 and 7.4, 6.7 and 7.3, 6.8 and 7.2, or 6.9 and 7.1, or about 7.0 at 25 °C. In some embodiments, the cleavage buffer conditions include 5-500 mM NaCl, for example 25-100 mM NaCl. In some embodiments, the cleavage buffer conditions include 1-100 mM Tris-HCl, for example 5-20 mM Tris-HCl. In some embodiments, the cleavage buffer conditions include 10- 1000 mM NaCl, for example 50-200 mM NaCl. In some embodiments, the cleavage buffer conditions include 5-500 mM Tris-HCl, for example 25-100 mM Tris-HCl. In some embodiments, the cleavage buffer conditions include 25-100 mM potassium acetate, 10-40 mM Tris-acetate, 5-20 mM magnesium acetate, and 50-200 pg / ml recombinant albumin, and the pH is between 7.6 and 8.2 at 25 °C. In some embodiments, the cleavage buffer conditions include 5- 20 mM bis-tris-propane-HCl, 5-20 mM MgC12, and 50-200 pg / ml recombinant albumin, and the pH is between 6.7 and 7.3at 25 °C. In some embodiments, the cleavage buffer conditions include 25-100 mM NaCl, 5-20 mM Tris-HCl, 5-20 mM MgC12, and 50-200 pg / ml recombinant albumin, and the pH is between 7.6 and 8.2 at 25 °C. In some embodiments, the cleavage buffer conditions include 50-200 mM NaCl 25-100 mM Tris-HCl, 5-20 mM MgC12, and 50-200 pg / ml recombinant albumin, and the pH is between 7.6 and 8.2 at 25 °C.

[0084] In some embodiments, the method further comprises amplifying the converted DNA or derivative thereof after treatment with an agent or a combination of agents that discriminates between methylated and unmethylated cytosine. In some embodiments, the method further comprises amplifying the extracted DNA or derivative thereof.

[0085] In some embodiments, the amplifying adds a sample barcode, and wherein a plurality of libraries each produced from a different sample are sequenced together in one sequencing lane. In some embodiments, the method further comprises performing size selection before or after the amplifying step.

[0086] Sequencing to Determine Methylation Status

[0087] The methylation status of the original sample DNA can be determined by sequencing the DNA. In some embodiments, the sequencing is next-generation sequencing or high-throughput sequencing.

[0088] DNA sequencing techniques, particularly high throughput next-generation sequencing techniques (often referred to as massively parallel sequencing techniques) such as those employed NOVASEQ (ILLUMINA), MISEQ (ILLUMINA), HISEQ (ILLUMINA), ION TORRENT (LIFE TECHNOLOGIES), GENOME ANALYZER ILX (ILLUMINA), GS FLEX+(ROCHE 454) etc., can be used for determining the sequences of the DNA to elucidate the methylation status of the original sample DNA. High throughput genetic sequencers are amenable to the use of barcoding (i.e., sample tagging with distinctive nucleic acid sequences) so as to identify specific samples from individuals thereby permitting the simultaneous analysis of multiple samples in a single run of the DNA sequencer. Methods as described herein that utilize NGS detection, in some embodiments can have an average depth of read of at least 0.1, 0.5, 1, 10, 50, 100, 200, 500, 1000, 2000, 2900, 3000, 3500, 4000, 5000, 10,000, 50,000, 75,000, 100,000, 130,000, 150,000, 175,000, or 200,000.

[0089] Methods herein can include analyzing data obtained from next-generation sequencing techniques. In some embodiments of methods herein, deaminated, or MSRE treated,methylation-transferred DNA molecules can be subjected to sequencing using next-generation sequencing techniques. For a skilled artisan, algorithm design tools are available that can be used and / or adapted to analyze the sequencing data. In addition, those skilled in the art can determine appropriate parameters for measuring alignment to a consensus sequence and / or to a known target region sequence, including any algorithms needed to achieve maximal alignment over the length of the sequences being compared.

[0090] Sequencing reads can be demultiplexed using an in-house tool and mapped using the Burrows-Wheeler alignment software, Bwa mem function (BWA, Burrows-Wheeler Alignment Software (see Li H. and Durbin R. (2010) Fast and accurate long-read alignment with Burrows-Wheeler Transform. Bioinformatics.) on single end mode using pear merged reads to the hgl9 genome. Amplification statistics QC can be performed by analyzing one or more of, but not limiting to, total reads, number of mapped reads, number of mapped reads on target, and number of reads counted.

[0091] Methods herein can include a background error model that can be constructed using normal, healthy, or non-diseased liquid samples, in illustrative embodiments, normal, healthy, or non-diseased plasma samples, which are sequenced on the same sequencing run to account for run-specific artifacts. In some embodiments, 5, 10, 15, 20, 25, 30, 40, 50, 100, 150, 200, 250, or more than 250 normal, healthy, or non-diseased liquid samples, in illustrative embodiments, plasma samples can be analyzed on the same sequencing run. The number of samples that can be sequenced on the same sequencing run can be in the range of 5 to 500, 5 to 400, 5 to 300, 5 to 250, 20 to 250, 30 to 250, 50 to 250, 75 to 250, 100 to 250, 50 to 500, or 100 to 500. Sample barcodes are used in illustrative embodiments. In some illustrative embodiments, 20, 25, 40, or 50 normal samples (e.g., plasma samples) can be analyzed on the same sequencing run. Outlier samples can be iteratively removed from the model to account for noise and contamination. In some embodiments, samples with a Z score of greater than 5, 6, 7, 8, 9, or 10 are removed from the data analysis. For each base substitution of every genomic loci, the DOR weighted mean and standard deviation of the error can be calculated.

[0092] Methods herein can include calculating percent identity that can be calculated by determining the number of matched positions in aligned DNA sequences, dividing the number of matched positions by the total number of aligned DNA sequences, and multiplying by 100. A matched position refers to a position in which identical nucleotides occur at the same position in aligned DNA sequences. The percent identity over a particular length can be determined by counting the number of matched positions over that length and dividing that number by the length followed by multiplying the resulting value by 100. A non-limiting example for calculating the percent identity, can be, if (i) a 500-nucleotide DNA target sequence is compared to a subject DNA sequence, (ii) an alignment program presents 200 nucleotides from the target DNA sequence aligned with a region of the subject DNA sequence where the first and last nucleotides of that 200-nucleotide region are matches, and (iii) the number of matches over those 200 aligned nucleotides is 180, then the 500-nucleotide nucleic acid target sequence contains a length of 200 and a sequence identity over that length of 90 percent (i.e., 180, 200x100=90).

[0093] In some embodiments, the uniformity in DOR can be measured using standard methods such as, but not limiting to, DOR slope, normalized median depth of read (nmDOR), or breadth of read (BOR). DOR slope represents the slope of the line in the linear portion of a list of loci sorted in descending DOR order. Closer to zero is better, as it represents a flat line. In some embodiments, the uniformity in DOR can be measured using the percent of reads in the 90th- 95th percentile. For this measurement, the loci are sorted in descending DOR order. In illustrative embodiments, a DOR distribution using the 90th-95th percentile contains 5 percent of reads. The reads of all loci between the 90th percentile and 95th percentile can be counted and divided by the total reads for all loci.

[0094] In some embodiments, the magnitude of the DOR slope can be less than 0.005, 0.001, 0.0005, 0.0001, 0.00005, 0.00001, 0.000005, or 0.000001. The magnitude of the DOR slope can be between 0 and 0.005, such as 0.000001 to 0.005, such as between 0.000005 to 0.00001, 0.00001 to 0.00005, 0.00005 to 0.0001, 0.0001 to 0.0005, 0.0005 to 0.001, or 0.001 to 0.005. The percent of reads in the 90th-95th percentile can be between 0.2 and 9 percent, such as between 0.2 to 8 percent, 0.2 to 7 percent, 0.2 to 6 percent, 0.4 to 9 percent, 0.4 to 8 percent, 0.4to 7 percent, 0.4 to 6 percent, 1 to 9 percent, 1 to 8 percent, 1 to 7 percent, 1 to 6 percent, 2 to 9 percent, 2 to 8 percent, 2 to 7 percent, 2 to 6 percent, 3 to 9 percent, 3 to 8 percent, 3 to 7 percent, 3 to 6 percent, 0.2 to 1.0 percent, 1 to 2 percent, 2 to 3 percent, 2 to 4 percent, 3 to 4 percent, 4 to 5 percent, 5 to 6 percent, or 6 to 8 percent, or 7 to 9 percent. In some embodiments of methods herein, the method can produce a composition comprising at least 100 different amplicons (e.g., at least 300, 500, 750, 1,000, 2,000, 5,000, 7,500, 10,000, 15,000, 19,000, 20,000, 25,000, 27,000, 28,000, 30,000, 40,000, 50,000, 75,000, or 100,000 non-identical amplicons) with the magnitude of the DOR slope in any of the ranges herein, or with a percent of reads in the 90th-95th percentile in any of the ranges herein. In some embodiments, different amplicons can range in between 100 to 500,000, 100 to 400,000, 100 to 300,000, 100 to 200,000, 100 to 100,000, 100 to 75,000, 100 to 50,000, 100 to 40,000, 100 to 30,000, 100 to 25,000, 100 to 20,000, or 100 to 15,000 non-identical amplicons.Preliminary Segmentation and Selection of Epigenetic Regions of Interest

[0095] In various embodiments, potentially informative regions of the genome are preselected computationally from the sequencing reads for downstream analysis, thereby significantly reducing the amount of data that need to be stored, analyzed, and otherwise manipulated. Using whole genome methylation sequencing data, example embodiments identify methylation cluster regions with high CpG density and co-high methylation, followed by genome segmentation to find methylation haplotype blocks for consideration in methylation biomarker selection. This preliminary segmentation drastically reduces the computational complexity, which in turn results in reduction in computational cost and time. It also guides the biomarker discovery towards more valid segments that satisfy the biological and sequencing technology priors. In addition, it reduces the number of probes needed to cover the designed panel.

[0096] As an initial step in example embodiments, a set of preliminary segments may be constructed by constructing a reference methylome, according to various embodiments. In some embodiments, this step can be performed using a common public reference methylome. In other embodiments, the preliminary segments can be constructed using a set of individual methylomesfrom each sample in a study cohort. In some embodiments, the preliminary segments can be constructed using reference methylomes of healthy / non-diseased samples, without using methylome data of tumor samples.

[0097] Example embodiments identify tightly and potentially co-methylated blocks across the genome. In example embodiments, the preliminary segmentation can be based on certain selected criteria. For example, as a first criterion, the preliminary segmentation can employ a threshold based on a certain primer or probe length, such as 75 bp to 150 bp (e.g., about 75 bp, about 80 bp, about 85 bp, about 90 bp, about 95 bp, about 100 bp, about 105 bp, about 110 bp, about 115 bp, about 120 bp, about 125 bp, about 130 bp, about 135 bp, about 140 bp, about 145 bp, or about 150 bp). As a second criterion, the preliminary segmentation can employ a threshold based on expected fragment lengths, such as between 60 bp to 140 bp (e.g., about 60 bp, about 65 bp, about 70 bp, about 75 bp, about 80 bp, about 85 bp, about 90 bp, about 95 bp, about 100 bp, about 105 bp, about 110 bp, about 115 bp, about 120 bp, about 125 bp, about 130 bp, about 135 bp, or about 140 bp). In some embodiments, the fragment length threshold is between 50 to 1200 bp, between 70 to 800 bp, between 100 to 200 bp, between 130 to 180 bp, between 50 to 200 bp, between 60 and 200 bp, between 60 and 150 bp, or between 60 and 100 bp. In some embodiments, the fragment length threshold ranges from 100 to 200 bp, from 120 to 180 bp, from 140 to 160 bp, from 150 to 170 bp, from 160 to 190 bp, or from 170 to 220 bp. In some embodiments, the fragment length threshold is less than 500, 400, 200, 150, 100, 90, 75, 70, 60, or 50 bp in length. As a third criterion, the processivity of the DNA (cytosine-5)-methyltransferase 1 (DNMT1) enzyme may be set from tens of base pairs to a few hundred base pairs.

[0098] For example, a threshold can be selected for the maximum allowable distance between adjacent CpG loci. The genome may be split into stretches in which the distance between adjacent CpGs are less than the threshold (coined as a ridge) and stretches of the genome devoid of any CpG (coined as a trench). In one embodiment, a threshold of about 50 bp, about 60 bp, about 70 bp, about 80 bp, about 90 bp, about 100 bp, about 110 bp, about 120 bp, about 130 bp, about 140 bp, or about 150 bp is selected for the maximum allowable distancebetween adjacent CpG loci, and ridges in which the distance between adjacent CpGs are less than 50 bp, less than 60 bp, less than 70 bp, less than 80 bp, less than 90 bp, less than 100 bp, less than 110 bp, less than 120 bp, less than 130 bp, less than 140 bp, or less than 150 bp are identified and selected for subsequent processing.

[0099] In some embodiments, any CpG that is available in less than a threshold (e.g., about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, or about 40% of total samples) is removed. In some embodiments, the ridges are computationally filtered to contain at least 3 CpG sites, at least 4 CpG sites, at least 5 CpG sites, at least 6 CpG sites, or at least 7 CpG sites. In some embodiments, the ridges are filtered to have a CpG density of at least 0.02 CpG / bp, at least 0.03 CpG / bp, at least 0.04 CpG / bp, at least 0.05 CpG / bp, at least 0.06 CpG / bp, or at least 0.07 CpG / bp.

[0100] To make the output of the block finding module more versatile, example embodiments use a lenient threshold for r-squared p-value, total number of CpGs in block, and distance between adjacent CpGs in block, but for each block also report the median r-squared, median Pearson r, median Euclidean distance, and median pairwise distance among all adjacent CpG pairs within the block as well as its CpG number. This information can later be used to further filter and narrow down the MHBs reported for each sample if desired.Annotation of putative DMRs / MBM

[0101] Pre-selected regions may be annotated with relevant information to aid in marker selection and prioritization as further discussed below. The annotations may cover three main categories:

[0102] (1) Structure / function: Genomic regions may be structurally and functionally annotated using a comprehensive collection of information containing the existing knowledge on the human genome. For each region, one or more of the following annotations may be included: distance to CpG regions (e.g., CpG island, shore, or shelf); position regarding genes (e.g., exon, intron, 3’UTR, 5’UTR, intergenic, TSS, first exon); overlap with regulatory elements (e.g.,promoter, enhancer, super-enhancer); enrichment for histone marks (e.g., histone methylation and acetylation marks associated with expression state); and multiple additional tracks for annotating transcription factor binding, IncRNAs, chromatin accessibility (DHS), etc. In some embodiments, this information may be pre-calculated for the human genome and imported from external resources (e.g., UCSC genome browser, annotationHub, chromHMM). Example embodiments may employ a module that runs bedtools in python to find overlaps for input regions of interest. Customizable parameters may include: minimum overlap in terms of fraction of input region lengths; minimum overlap in terms of fraction of genomic element lengths; total number of base overlaps reported; etc. As shown in the FIG. 10 schematic, the “intersect” function with the -wa and -wb parameters will return origin entries in A (the input CpG regions bed file) and report specifically the type and size of overlaps (-wao) with additional bed files (e.g., Bl and B2), which would be the annotation tables in our module.

[0103] (2) Fragmentation: Example embodiments include a module that uses plasma cfDNA data to characterize the fragmentation pattern of a given region in healthy / non-diseased cfDNA. This module may further add annotation columns for fragmentation and report overall characteristics and distribution of fragment lengths, end motifs, and other fragmentation metrics. This module may be used for downstream marker selection and prioritization, as discussed above, potentially combining fragmentation information with methylation in targeted sequencing of patient plasma.

[0104] (3) Literature DMRs: In addition to the above functional and structural annotations, previously identified regions of the human genome harboring CpG clusters and cancer DMRs may be added as separate columns in the output. The goal is to specify if each candidate biomarker region overlaps with independently identified regions previously reported in the literature as DMR or other relevant association.

[0105] Example embodiments include: a script to receive genomic regions as input in .bed format and output an annotated .bed file with multiple columns added based on user- selected annotations from the list of available annotations; a script to use available sequencingdata for characterization of fragmentation profiles in genomic regions of interest; a confidence level assigned to each region based on existing evidence (e.g., known CRC markers) to help in marker ranking and prioritization; and visualization summary plots for overlaps with known annotations.Methylation Biomarker Selection

[0106] Biomarkers generally are informative regions that contain differential signals between different cohorts (e.g., between individuals with cancer and healthy or non-cancerous individuals). In terms of methylation biomarkers, informative regions typically have two main characteristics: (i) CpG loci are co-methylated in these regions, and (ii) they correspond to distinct functional domains (i.e., each region captures one or similar functional features). How to identify and score such biomarker regions will be further discussed below, including an example modeling approach that identifies putative biomarkers by comparing the methylation and comethylation patterns between different cohort samples in different regions and identifying differentially methylated genomic regions. The various illustrative approaches and embodiments disclosed herein improve and expand on existing methods by, for example, inferring the methylation state of a tentative biomarker through modeling the processivity of DNMT1 by jointly modeling adjacent CpG loci methylation patterns; considering each read’s mapping quality in such joint modeling; and benchmarking different models of varying complexity.(i) Methylation Haplotype Measures

[0107] In various embodiments, with reference to FIG. 7, the analysis may optionally implement and compare the methods developed in the literature (e.g., Methylation Entropy from Xie et al. (2011), Epi-Polymorphism from Landau et al. (2012), and Methylation Haplotype Load from Guo et al. (2017)) to score the methylation status of a genomic region as a function of the observed methylation patterns of the fragments in that region. These models and methods may be used as a baseline for the method described herein to infer the methylation status of the CpG loci in the WGBS data across samples. Example embodiments identify regions where themethylation status is almost constant in a given region across samples, and identify regions which are significantly differential between samples. In example embodiments, this approach also prioritizes each region based on its association with different clinical covariates.

[0108] To achieve robustness in the methylation inference model and to guide the inference, example embodiments may leverage publicly available methylation datasets to construct CpG methylation status prior distributions. A unified framework may be employed to fetch methylation status of CpG loci in a given genomic region. As examples, the Human Methylome Atlas, Roadmap Epigenetics, and Blueprint Epigenome may be used for tissue and cell-type specific methylation prior distributions, and Fox-Fisher (2021) may be used for bulk plasma and white blood cell methylation prior distributions.

[0109] Example embodiments consider a Markovian process to infer the methylation status of a CpG locus and capture the patterns of CpG co-methylation in a methylation haplotype block by leveraging read- level information. Various embodiments implement probabilistic modeling of the DNMT 1 methylation mechanism in order to accurately infer the methylation state of a tentative biomarker (see FIG. 8). The processivity and substrate-specificity of methyltransferases may be modeled via a Hidden Markov Model.

[0110] In various embodiments, a methylation score is used to capture the level of comethylation in a given methylation haplotype block. This score offers an estimate for the total methylation level as well as the level of co-methylation in a given window and forms part of a module called CpGBlocks. In example embodiments, the CpGBlocks module is packaged in ProcessSegmentation, as further described below.(ii) Process Segmentation of Methylation Haplotype Blocks

[0111] In various embodiments, one of the main steps of identifying methylation biomarkers is to define the notion of a “region.” For example, a biomarker may be a region where the methylation score (e.g. the output of the methylation haplotype measure) is as uniform as possible under a loss function (e.g., maximize a likelihood or minimize a negative loglikelihood) within each sample type or population yet different across different sample types or populations. In some embodiments, a biomarker region may be a region where the methylation scores of all CpGs in that region can be approximated as a constant function within each sample type or population.

[0112] In example embodiments, to further refine the identified sample- specific MHBs into smaller regions where CpGs are co-methylated under the defined MHM across multiple samples, the CpGBlocks module is packaged in ProcessSegmentation, which is a generalized module for fitting a piecewise constant function to methylation load signals which are exponential family distributed. Example embodiments apply the model to the observed MHM values on all MHBs across all samples to identify regions of constant methylation state across multiple samples. The Methylation Haplotype Measure is applied to all samples and then the Process Segmentation model applied to the signal to identify the genomic blocks. This step provides as output the number of blocks, their lengths, and their scores.

[0113] For example, suppose that the observed methylation statuses are realizations of independent random variables

[0114] Further assume that the support for each parameter is divided intoK contiguous, non-overlapping intervals0 K. Example embodiments model the distribution ofkas independent and identicallydistributed (“IID”):

[0115] Under this model the log-likelihood may be written as LK= ’ which can be solved via dynamic programming.

[0116] In example embodiments, a probabilistic model is constructed to infer the methylation status of the CpG loci. There are multiple advantages to the probabilistic modeling of methylation status rather than using deterministic functions that are tailored to estimate methylation load: (i) various embodiments make the generative model as close as possible to the biological explanation of the CpG methylation patterns; (ii) various embodiments can leverage publicly available information to construct priors and inject these priors at different levels of the model; (iii) hypothesis testing can be performed very naturally as these models can be fully investigated; and (iv) inference comes with uncertainty estimation. Example embodiments first infer the methylation status of all CpGs in a genomic window by assuming that the CpGs are independent then add the dependence structure between these loci and perform inference.

[0117] Example embodiments design and implement a model to fit a piecewise constant function to simulated values. A Bayesian approach (e.g., a fully variational Bayesian approach or an exact inference Bayesian method) to the process segmentation problem may be employed; for example, a Bayesian method for gaussian distributed signal. Example embodiments extend such a model to beta-binomially distributed signal where Stochastic Variational Bayes (SVI) is used instead of exact inference.

[0118] In example embodiments, the prior distribution of the break-points can be constructed from publicly available DMRs (e.g., Guo et al. (2017), Benelli et al. (2021), Loyfer et al.(2022), Roadmap Epigenomics Project). In order to estimate the “optimal” number of breakpoints (i.e., segments), multiple methods may be employed. Example embodiments formalize this model selection criterion as a penalty term in a penalized log-likelihood maximization:where L is the penalized likelihood and K is the optimal number of breakpoints. Table 1 depicts different criteria for model selection:

[0119] Example embodiments fit a change point estimation model to the methylation load signal. The inferred change points indicate the boundaries of the regions where the signal is almost constant. These regions will in turn be passed to the next pail of the discovery pipeline for scoring and prioritization.

[0120] Given a sequence y = (yi,...,yn) of methylation levels of n consecutive CpG sites, assuming each is independently distributed according to a normal distribution, the data likelihood is:

[0121] Example embodiments model the segmentation problem as a regression where the function is piecewise constant. That is, given k boundaries 0 = t0< t1<. . . < t!i-1< tk= n the true signal is generated from a function f which is constant on+ 1, ... , tqJvO < q < k. Therefore y is IID distributed within each segment. An objective is to estimate the number of distinct regions k, the location of the boundaries of these regions t = (tx. tjJ), and region methylation levels p. = (p.lt... ,Jufc).

[0122] With respect to the model, example embodiments start by assuming priors over parameters of interest. Assuming a uniform prior over the number of segments k, a uniform prior over all segmentations into k segments, and a Gaussian distribution over the methylation level with parameters v and p2, the prior distribution takes the following form:P(^|v, p)P(t)P(k)(iii) Identifying, scoring, and prioritization of DMRs

[0123] Having identified the differentially methylated regions and inferred the methylation status of each CpG in each of the regions, example embodiments compare scores from above (e.g., differential methylation score) across cohorts and test for significant differences, which will result in a set of differentially methylated biomarkers.

[0124] Example embodiments develop baseline models based on available methods from the literature (e.g., Benelli (2021), Loyfer (2022), and Guo (2017)). For example, WGBS Tools, simple t-tests or Area Under the Curve (AUC) from the Receiver Operator Characteristic (ROC) curves may be used to call a biomarker as significantly differential.

[0125] One of the main advantages of the disclosed Bayesian probabilistic modeling is that as part of the inference, example embodiments infer the probability distribution of the unknown parameters, in this case CpG methylation status. Having access to the distributions, estimating the probability of the two distributions being different is relatively not computationally demanding.

[0126] In various embodiments, sets of published DMRs from the literature can be used as inputs to the disclosed MHM measure and the level of concordance between the disclosed score and hypo / hyper methylation status of these regions can be compared. ROC curves of predicting hypo- / hyper-methylated status of these biomarkers can be plotted.

[0127] Example embodiments construct control regions from GenomelnABottle (GIAB) Stratifications, an application programming interface (API) for the Genome In A BottleStratifications project. These stratification files were developed as a standard resource of Browser Extensible Data (BED) files (a text file format used to store genomic regions as coordinates and associated annotations) for use in stratifying true positive, false positive, and false negative variant calls in challenging and targeted regions of the genome. Example embodiments annotate biomarker regions in terms of Genome In A Bottle stratification. Difficult-to-map regions should not have a statistically significant overlap with biomarkers discovered according to the disclosed embodiments. Example embodiments add some of the regions to the final panel as negative controls, which should not be differentially methylated if other parts of the mapping I processing is correctly performed. Example embodiments create a list of genomic loei / regions with high noise, high repeat, or containing no CpGs. This list of blacklist regions can be used as negative controls.

[0128] Example embodiments prioritize the identified candidate biomarkers for inclusion in a final panel based on certain criteria. In some embodiments, the identified candidate biomarkers are prioritized based on clinical data (e.g., sex, age, ethnicity, etc.). Example embodiments use feature scoring methods to score methylation biomarkers set by accounting for the methylation signal correlations of DMRs and prioritize them for their varying predictive powers across subpopulations (e.g., cancer subtypes, high-risk populations, age, gender, ethnicity, ctDNA fractions, etc.).

[0129] In various embodiments, a Constrained Probability Sampling (CPS) module is used for sampling from a population under multiple probability constraints. Example embodiments score each biomarker region based on their predictive power. Then the prioritization problem is stated as a constrained optimization problem where the objective function is the sum of these scores such that the cohort constraints are met; for example, the ethnic diversity of the cohort is a good representative of the target population.

[0130] Various embodiments assign a differential power, di(syk), i 6 1, ... , N,j 6where N is the total number of biomarkers, I is the number of samples in cohort k, and K is the total number of cohorts, as the AUC of the ROC curve of differentiatingbetween the cohorts. The problem can then be formalized as the following optimization problem:

[0131] For different constraint thresholds, this problem can be solved to prioritize the topM biomarkers under length constraints, ethnicity, sex, age, etc.

[0132] In example embodiments, an output of this analysis is a list of target regions that is balanced in terms of predictive power across subpopulations along with functional annotation and GIAB classification.File Format for Fragment Level Methylation Data Manipulation and Representation ToolBox

[0133] To facilitate efficient analysis of a large set of sequencing data, such as whole genome methylome data, various embodiments disclosed herein incorporate and use a novel file format that improves upon and overcomes the shortcomings of other available file formats. For example, regular bam files are too large and typically contain more information than necessary. Other available binary formats (such as pat file from WGBSTools) do not faithfully conserve fragment level information and are not portable; that is, in order to read, annotate, or otherwise manipulate these files, one needs to utilize specific toolbox or libraries, which may require developing new interfaces for manipulating these files. The file format embodiments disclosed herein allow preservation of fragment level information, including mapping quality information, by representing each fragment on a separate line and scoring each fragment based on the phred score of the CpGs in the fragment and the MAPQ score. The disclosed file format embodiments accommodate efficient file storage without loss of relevant information for downstream processes for all DNA methylation sequencing data, and allow archiving of all fastq or bam files on any cloud platform, e.g. DNANexus, Google Cloud Platform or Amazon AWS, while directly providing convenient input to downstream analyses. In various embodiments, with the disclosed file format, files can be read, annotated, or otherwise manipulated using commonly used bedtoolsand basic table editing software. In some embodiments, standard visualizations for read-level representation of CpG haplotype block methylation status are implemented.

[0134] Example embodiments provide a file format to concisely represent CpG methylation patterns in a human-readable format - e.g., text instead of binary - such that mapping quality information is preserved and provides portability in a sense that it is manipulatable using commonly-used tools, such as BEDtools, and basic table editing software. Example embodiments implement standard visualizations for read level representation of CpG haplotype block methylation status.

[0135] In order to identify, annotate, and interpret DMRs, obtained as discussed above, example embodiments use fragment-level methylation information to infer the methylation status in a genomic region. Regular BAM files are too large and also contain more information than necessary. Other available formats (e.g., .pat from WGBSTools) are binary formats which have two main shortcomings: (1) these files are not portable - that is, in order to read, manipulate, or annotate these files, one needs to utilize specific toolbox / libraries which necessitate developing new interfaces for manipulating these files; and (2) these formats do not faithfully conserve fragment level information. In example embodiments of the disclosed file format, this information can be preserved by, for example, representing each fragment on a separate line. Each fragment is also scored based on the phred quality score of the CpGs in the fragment and the MAPQ score.

[0136] Example embodiments accommodate efficient file storage without loss of relevant information for downstream processes for all DNA methylation sequencing experiments in the future, such as deep WGBS samples from the DNA methylation biomarker discovery discussed above. Embodiments of the disclosed file format will allow archiving of all FASTQ or BAM files on any cloud platform, such as DNANexus, Google Cloud Platform, or Amazon AWS, while directly providing convenient input to downstream analyses. Also, example embodiments provide the ability to present the innovative analyses algorithms and resulting summarization developed through methylation biomarker discovery.

[0137] .cpg Constructor: Example embodiments provide for a .cpg file format that is used to represent methylation patterns in a given genomic region at the fragment / read level. Example embodiments provide multiple visualization tools to represent the methylation patterns of CpG loci in a given genomic interval. For example, “CpG Heatmap” provides a heatmap of fragment / read level methylation patterns in a given genomic window, and “CpG Tracks” provides stacked barplots representing methylation status in each CpG loci in a given interval. This allows for the implementation of tools and visualizations to represent methylation haplotype blocks in such a way that captures patterns of co-methylation within genomic windows.

[0138] Table 2 illustrates example embodiments of the .cpg file format (see FIGs. 13 and 14), with each row representing a fragment. In Table 2, chrom: chromosome, start: start of the fragment, end: end of the fragment - the beginning and the end of the fragment are inferred from the BAM file, cpg methylation pattern: methylation state of cpgs in the fragment as well as their loci in a CIGAR string compliant format, score: -101ogl0(p) where p is 1 - accuracy of each fragment in calling each base correctly.

[0139] In the case of paired-reads, example embodiments may summarize the fragment information using the following conventions: “start” of the fragment is the minimum of the two reads’ start coordinates; “end” of the fragment is set to the end of the two reads; “cpg methylation pattern” of the fragment is set to the methylation state if the two reads match, and in case they do not, example embodiments set it to the state to N. If the CpG is covered only by one of the reads in a pair, the CpG methylation status is set according to that one read. Previous approaches to paired end read alignment merger did not combine reads if they do not overlap, which can be very prevalent in WGBS data.

[0140] Using the .cpg file format as disclosed herein enables efficient extraction of CpG methylation information from bismark output. Example embodiments of the .cpg file format provide numerous advantages over the existing formats, such as:

[0141] (1) Preservation of fragment level methylation information: .cpg files are lossless representations of the sample CpG methylation information. In effect, each line represents a single fragment.

[0142] (2) Portability: unlike other file formats (such as .pat from WGBSTools) CpG files are viewable using any text viewer / editor (such as vim, emacs, and less), or spreadsheet software (e.g., Google Spreadsheet or Microsoft Excel). No special tool is needed for reading the .cpg files.

[0143] (3) Compatibility: CpG files are tab-delimited table format with headers and thus compatible with most common table manipulation software (e.g., pandas, R) and genomic interval manipulation packages (e.g., BedTools or intervaltree).

[0144] (4) Compressibility: Because only relevant information (e.g. information related to CpG methylation) is retained, example embodiments of the CpG files offer at least lOx, 20x, 30x, 50x, lOOx, 150x, or 200x compression relative to the BAM files.

[0145] Example embodiments allow for conversion of a bam file, which is the output of the bismark software, to a .cpg file in one step using the CpGReads package. For example:CpGReads.convert_bismark_bam_to_cpg(input_bam_fpath, output_cpg_fpath, compress=True)

[0146] If compress = True, the output will be compressed and saved as a .cpg.gz which can be loaded the same way as a regular .cpg file.

[0147] In example embodiments, once CpG files are constructed, they can be loaded using the following command, whether the input is a compressed .gz file or not. For example: cpg_reads = CpGReads. load_from_cpg(output_cpg_fpath)

[0148] Having instantiated a cpg_rcads object, one can parse the methylation patterns using, for example: cpg_reads .expand_cpg_pattem()

[0149] Now the user has the pandas machinery to efficiently query, sort, search these datasets. For example: cpg_reads.query("chrom == @region.chrom").query("start >= ©region. start and end <= @region.end").sample(frac=.01).sort_values(['start', 'end'])

[0150] Example embodiments of this module are able to handle both single-end and paired-end reads. Paired-end reads are especially very useful in cell-free DNA analysis, but processing paired-end runs require much greater care and effort.

[0151] CpG Loci Visualization Tool: Example embodiments provide a CpG loci visualization tool that uses the .cpg file format as an input and retrieves the CpG methylation pattern of the fragments in a .cpg file as a color coded heatmap. These plots facilitate exploratory data analysis and quality control as well as publication quality visualizations for posters / publications. These plots provide the ability to visualize discrete as well as continuous heatmaps such that they can be used for visualization of methylation level (0) values data.

[0152] Example embodiments provide user-friendly, publication quality visualization tools (e.g., included in CpGReads) to plot fragment-level methylation patterns. Example embodiments enable obtaining plots by:

[0153] Fragment level methylation pattern plot of CpG loci only: cpg_reads_region.plot(kind='heatmap', compact=True, annotate=True, ax=ax)

[0154] Plotting methylation information of all loci in a given region: cpg_reads = CpGReads .load_from_cpg(output_cpg_fpath) cpg_reads_region = cpg_reads.query("chrom == ©region. chrom").query("start >= ©region. start and end <- ©region. end"). sample(frac=.O 1 ).sort_values([ 'start', 'end']) cpg rcads rcgion.plottkind-'hcatmap'. compact=False, annotate=False, ax-ax)

[0155] Code to plot population level CpG matrices (see FIG. 17):= HybridCaptureSampleManifest.load_hybrid_capture() sample_ids = hc_sample_manifest.sample_id.values# Loading target regions as a RegionManifest region_manifest = RegionManifest.from_bed(regions_bed_fpath, assembly='hgl9').attach_region_ids()# Loads fragment information region_manifest = hc_sample_manifest.load_fragments_in_regions(region_manifest, n Jobs) cpg_matrices = CpGReads.cpgreads_list_to_cpg_matrices(region_manifest [samplejds], sampling_frac)CpGReads.plot_cpg_matrices(cpg_matrices, samplejds, out_fpath)

[0156] Methylation Block Visualization: Example embodiments provide visual representation of DNA co-methylation levels across genomic regions of interest. It has previously been established that due to processivity of DNA methyltransferase enzymes (DNMTs), adjacent CpGs present concordant methylation states (typically within 100 bp distance). Therefore, regions of tightly correlated methylation called co-methylation blocks are discovered for pre-selection. When correlation matrices are measured and plotted, these block regions can be visualized in the form of triangles (e.g., FIGs. 18 and 19) of high correlation as shown above.

[0157] Example embodiments provide functionality that is compatible with other methylation modules in python (e.g., as discussed above). More specifically, example embodiments of this function will receive the .cpg file as input and process the file using functions to load, query regions, and convert methylation haplotypes to numeric matrices developed as part of the CpGreads module. Next, the function calculates and plots the correlation matrix (or linkage disequilibrium, controlled by the “method” parameter) for all CpGs within the given region of interest purely using python functionalities.

[0158] Example embodiments provide tools for visualizing CpG co-methylation (LD or Pearson correlation) and fraction methylation (beta-value) as part of the CpGBlocks module. An example usage of this on a CRC sample in a given region of interest (target 675 in hybrid capture (HC) panel):

[0159] Following is a code snippet for creating triangle plots in an exemplary embodiment: from ecd.methylation.cpgreads import CpGReads from ecd.methylation.cpgblocks import CpGBlocks cpgreads = CpGReadsdoad_from_cpg(path_to_cpg_file).query("chrom == @region.chrom").query("start >= ©region. start and end <= ©region. end")CpGBlocks(cpg_reads_region) ,plot_triangle_from_cpg(output_path=" . / " , clustering= 1 , mcthod-'corr', highlights=list_of_cpg_loci_to_highlight)

[0160] One application of the Methylation Block Visualization tool is for comparing multiple regions for marker selection. In an example, 627 marker regions were included in a hybrid capture (HC) targeted panel. By quantifying and visualizing the level of co-mcthylation among CpGs in different target regions, it is possible to filter and prioritize target regions. For instance, FIG. 19 shows two example regions (targets 1 and 2). Both targets show decent comethylation in CRC samples which is desirable. However, only target 2 also shows some level of correlation in cfDNA controls.

[0161] As illustrated, CpGReads provides the capability to process BAM files and convert them to a considerably compressed format, .cpg, which is highly portable compared to the s.o.t.a in linear time O(LL). This library also offers publication quality plots for performing EDA on methylome sequencing data.Compute-Implemented Systems and Methods

[0162] Various operations described herein can be implemented on computer systems having various configurations. Referring to FIG. 1, in various embodiments, a system 100 may include a computing system 110 (which may be or may include one or more computing devices,co-located or remote to each other), a sequencing system 160 (capable of, e.g., generating DNA sequencing data), an information system 170 (such as a management or clinical information system that may record and / or provide information regarding samples or patients), vessels 175 (e.g., for holding samples), sample processing system 180 (e.g., a system that may include robotic components 182 for preparing, moving, and / or processing samples), and imaging and / or therapy systems 190 (which may include e.g., treatment unit 192 and imager / sensors 194 for imaging patients using various imaging modalities, providing treatments such as radiotherapy, and / or performing other evaluation or therapeutic procedures based on what is learned from patient samples). The computing system 110 (e.g., one or more computing devices) may be used to control and / or exchange signals and / or data with sequencing system 160, sample processing system 180, information system 170, and / or imaging and / or therapy systems 190, directly (e.g., through wireless and / or wired communication) or indirectly via another component of system 100 (e.g., via any combination of wireless and / or wired communication). In certain embodiments, computing system 110 may be used to control and / or exchange data or other signals with sequencing system 160, information system 170, sample processing system 180, and / or imaging and / or therapy systems 190. The computing system 110 may include one or more processors and one or more volatile and / or non-volatile memories for storing computing code and data that are captured, acquired, recorded, and / or generated.

[0163] The computing system 110 may include a controller 112 that is configured to exchange control signals with sequencing system 160, information system 170, sample processing system 180, and / or imaging and / or therapy systems 190, and / or any components thereof, allowing the computing system 110 to be used to control, for example, processing of samples, capture of images, acquisition of signals by sensors, positioning or repositioning of samples being tested or imaged, recording or obtaining other information, and / or running assays or tests.

[0164] A transceiver 114 allows the computing system 110 to exchange readings, control commands, and / or other data or signals, wirelessly or via wires, directly or indirectly via networking protocols, with, for example, other components of system 100. One or more userinterfaces 116 allow the computing system 110 to receive user inputs (e.g., via a keyboard, touchscreen, microphone, camera, biometric scanners, etc.) and provide outputs (e.g., via a display screen, audio speakers, light emitters, etc.) with users. The computing system 110 may additionally include one or more databases 118 for storing, for example, data acquired from one or more systems or devices, signals acquired via one or more sensors, sequencing data, biomarkers, images, etc. In some implementations, database 118 (or portions thereof) may alternatively or additionally be part of another computing device that is co-located or remote (e.g., via “cloud computing”) and in communication with computing system 110, sequencing system 160, information system 170, sample processing system 180, imaging and / or therapy systems 190, and / or components thereof.

[0165] Imaging and / or therapy systems 190 may include a treatment unit 192, which may include any systems and / or devices employed to administer a treatment to a patient, such as a radiation therapy system. Imager and / or sensors 194 may be or may include, for example, any system or device that is involved in, for example, capturing images of patients and / or samples. Imagers may include detectors for visible light and / or light in any frequencies of interest, such as (but not limited to) the spectrum from infrared to ultraviolet. Imagers may employ any suitable optical components (e.g., lenses, mirrors, filters, beam splitters, prisms, diffusers, diffraction gratings, etc.), digital components (e.g., charge-coupled devices (CCDs), as well as an area for placement of samples, computing components (e.g., one or more processors, such as digital signal processors) to process and / or pre-process images, etc. Imagers may be, or may employ, any microscopes or microscopy systems (e.g., confocal microscopy), tools, and / or techniques that will provide the desired imaging data. The imager and / or sensors 194 may have the capability of receiving control signals from a computing device or system to, for example, initiate or cease image capture, and / or return images or other imaging data or status signals to the computing device or system (e.g., computing system 1110). Imaging and / or therapy systems 190 may include any tools for obtaining additional data about samples and / or patients (such as spectrometers, chromatographs, etc.). Sensors may be used to detect, for example, other aspects of samples and / or patients, such as temperature, humidity, location, etc.

[0166] Sample processing system 180 may include any components used to automate preparation of samples and running tests on samples. Robotics 182, for example, may include any combination of actuators, stepper motors, servomotors, control system, robot arms, end effectors like grippers and manipulators, etc. Robotics 182 may be, or may comprise, for example, an automated robotics system with process automation software. In various embodiments, robotics 182 may employ vessels 175, such as vials or plates, that can be moved and manipulated, for example, for positioning of samples to be evaluated using sequencing system 160 or components thereof. Sample processing system 180 may include components that may be used to maintain the integrity of samples during storage, transport, and testing, such as heaters, passive or active coolers, etc. Sensors may be used by sample processing system 180 to, for example, monitor, guide, and evaluate the progress of tests (e.g., by detecting temperature, fill level of vessels, or other states or conditions). Sequencing system 160 may include sequencing platforms or devices as well as various analytical tools used to process data from the sequencing platforms. Analytical tools may include software and / or hardware used to generate computer files with raw and / or processed sequencing data.

[0167] In various implementations, components of system 100 may be rearranged or integrated in other configurations. For example, computing system 110 (or components thereof) may be integrated with one or more of the sequencing system 160, sample processing system 180, and / or components thereof. The sequencing system 160, sample processing system 180, and / or components thereof may be directed to a vessel 175 in which a sample can be situated (e.g., so as to test or evaluate biological samples). In various embodiments, the vessel 175 may be movable (e.g., using any combination of motors, magnets, etc.) to allow for positioning and repositioning of samples (such as micro-adjustments for positioning of samples to be sequenced). It is also noted that not all components of system 100 are required to implement the disclosed approach, and in various embodiments, only a subset of the components of system 100 may be employed. For example, in various embodiments, computing system 110 may obtain and process data that was obtained via sequencing system 160 or another system that is or is not in direct communication with the computing system 110. In certain embodiments, data may beobtained for samples that were not processed in an automated fashion but rather manually by one or more users.

[0168] A data acquisition unit 124 may retrieve, acquire, or otherwise obtain various data, such as sequencing data. The data acquisition unit 124 may, for example, obtain data stored in database 118, sequencing system 160, information system 170, sample processing system 180, and / or imaging and / or therapy systems 190. An interaction unit 126 may interact (e.g., via user interfaces 116) with users (e.g., laboratory technicians, data scientists, clinicians, etc.) to obtain information or commands needed for system 100 or components thereof to function, or to start operations, repeat processes, and / or stop operations. In certain embodiments, the data acquisition unit 124 may obtain data from users via interaction unit 126.

[0169] A preprocessor 128 may perform any number of steps disclosed herein in preprocessing sequencing data. Machine learning platform 130 may be configured to train and update machine learning models, as further discussed herein. Machine learning platform 130 may, for example, employ certain machine learning techniques and algorithms to train and update predictive models. Machine learning platform 130 may include a training engine 132 which may, for example, fit models to sequencing data. The training engine 132 may, for example, obtain sequencing data from or via data acquisition unit 124, sequencing system 160 or components thereof, and / or information system 170. Inference engine 134 may apply models (e.g., models obtained from machine learning platform 130 or components thereof) to generate outputs as disclosed herein. Biomarker generator 140 may perform analyses on data from machine learning platform 130 to, for example, generate biomarkers to be used for various conditions or sub-populations.

[0170] A reporter 142 may generate reports that include, for example, information on sample sequencing (e.g., via sequencing system 160 or components thereof), imaging or administration of treatments (e.g., via imaging and / or therapy systems 190 or components thereof and / or via information system 170), model training (e.g., via machine learning platform 130), and biomarker generation (e.g., via biomarker generator 140). For example, reporter 142may provide or identify trained and / or updated models, and / or biomarkers. In certain embodiments, reporter 142 may obtain information to be reported from, for example, database 118 and / or information system 170. Data that may be reported may be, for example, transmitted to another system or device (which may or may not be part of system 100), saved in non- transitory computer-readable storage media (e.g., database 118, information system 170, and / or elsewhere), and / or presented or otherwise provided to users (e.g., via a display device that is part of user interfaces 116).

[0171] Referring to FIG. 2, an example process 200 is illustrated, according to various example embodiments. Various elements of process 200 may be implemented by or via system 100 or components thereof. Process 200 may begin at block 210 with obtaining DNA samples from healthy subjects (i.e. subjects not exhibiting a phenotype of interest) and subjects exhibiting the phenotype (e.g., a disease of interest), and perform methylation sequencing of the DNA.

[0172] At block 220, process 200 includes constructing one or more files (e.g., one or more .cpg files) based on sequencing data obtained from block 210. In various embodiments, the input data is the output of any methylation mapping / alignment tool (e.g., Bismark), usually in a BAM / SAM (Binary Alignment Map / Sequence Alignment Map) format. CpG files capture the methylation status of all CpG sites within a mapped DNA fragment. Each line of a cpg file corresponds to a DNA fragment that is specified by chromosome, start and end coordinates and the CpG methylation information within that fragment is encoded via a novel encoding method. In some embodiments, given a set of CpG sites captured by a fragment, the methylation status of each site is encoded as the number of base pairs from the beginning of the fragment, followed by the methylation status. Given a fragment with coordinates chrZ;X-Y and CpG sites located on this fragment with coordinates chrZ:x_l, chrZ:x_2, chrZ:x_3, the encoding will be (x_l- X)s_l(x_2-xl)s_2(x_3-x_2)s_3 where s_i is the methylation status of the CpG site x_i, i.e. C for methylated, T for unmethylated and N for undetermined. For example: Consider a fragment with the chromosome, start and end coordinates as chrl:I-100, and CpG sites chrl:20, chrl:40, and chrl:60 captured by this fragment where the first site is methylated and the rest areunmethylated. In this case, the encoding will be 19C20T20T. This allows conservation of storage space and thus reduces the amount of computational resources required.

[0173] At block 230, process 200 includes preliminarily segmenting the data in the generated files. In this step, blocks of CpG sites where the maximum distance between adjacent CpG sites are less than a threshold are identified. In various embodiments, the threshold is generally or typically chosen based on biological priors (e.g. chromosome boundaries, cytobands, etc.) and sequencing technology (e.g. maximum read length). This step guides further inference models and helps ensure that discovered biomarkers are designable (for example, the designability of probes or primers used for enrichment of DNA fragments comprising the biomarkers) and make biological sense. This also reduces the computational time and cost of the inference by transforming a relatively complex regression problem into a number of smaller ones. Table P02 include(s) ridges (chr 21, 22) that may be generated by this preliminary segmentation process according to various embodiments.

[0174] At block 240, process 200 includes generating candidate biomarkers using a suitable model. In various embodiments, regions resulting from block 230 are used as inputs to a segmentation model, which further segments the regions into smaller regions where CpGs are co-methylated within each cohort. For example, a region where CpG sites are strongly comethylated are segmented into fewer segments compared to a region with the same number of CpG sites where the CpG sites are not as strongly co-methylated. In example embodiments, the segmentation model is a Bayesian segmentation model, where segmentation robustness is increased naturally via modeling methylation signal variance as well as the expected value. Table P05 include(s) DMRs that may be generated by this modeling process according to various embodiments.

[0175] At block 250, process 200 includes analyzing candidate biomarkers to obtain a select set of biomarkers. Analyzing the candidate biomarkers may include scoring the candidate biomarkers. Scores for the candidate biomarkers can be used to prioritize the candidate biomarkers, such that the candidate biomarkers can be ranked based on their scores (e.g., fromhighest scores to lowest scores). For example, candidate biomarkers with relatively higher scores, or having scores above a threshold value, or having scores falling within a first range of values, may be deemed to be relatively more likely to distinguish between healthy subjects (i.e. subjects not exhibiting a phenotype of interest) and subjects exhibiting the phenotype, and candidate biomarkers with relatively lower scores, or having scores below the threshold value, or having scores falling within a second range of values, may be deemed to be relatively less likely to distinguish between the healthy subjects and the subjects exhibiting the phenotype. Table P04 include(s) biomarkers (chr 21, 22) that may be generated by this scoring and / or prioritization process according to various embodiments.

[0176] In various embodiments, each candidate bio marker is scored on the signal-to- noise ratio (SNR) with the aim of prioritizing regions where the background noise (e.g., healthy methylation signal) is minimal compared to the phenotype signal (e.g., the cancer signal). The candidate biomarkers can be prioritized based on a number of criteria, such as designability of probes or primers for the biomarkers. In some embodiments, biomarkers in repeat or low- complexity regions are deprioritized.

[0177] At block 260, process 200 includes using the ranked I prioritized I selected biomarkers from block 250 to develop a panel to detect the phenotype (e.g., colorectal cancer) in a patient or other subject. For example, a sample (e.g. a blood, plasma, serum, or urine sample containing cell-free DNA) from a patient who may have a phenotype can be analyzed as disclosed herein, with primers or probes designed based on the selected biomarkers and used to evaluate likelihood of having the phenotype.

[0178] FIG. 22 shows a simplified block diagram of a representative server system 2200 (e.g., computing system 110 or other components in FIG. 1) and client computer system 2214 (e.g., computing system 110, sequencing system 160, information system 170, and / or sample processing system 180) usable to implement various embodiments of the present disclosure. In various embodiments, server system 2200 or similar systems can implement services or serversdescribed herein or portions thereof. Client computer system 2214 or similar systems can implement clients described herein.

[0179] Server system 2200 can have a modular design that incorporates a number of modules 2202 (e.g., blades in a blade server embodiment); while two modules 2202 are shown, any number can be provided. Each module 2202 can include processing unit(s) 2204 and local storage 2206.

[0180] Processing unit(s) 2204 can include a single processor, which can have one or more cores, or multiple processors. In some embodiments, processing unit(s) 2204 can include a general-purpose primary processor as well as one or more special-purpose co-processors such as graphics processors, digital signal processors, or the like. In some embodiments, some or all processing units 2204 can be implemented using customized circuits, such as application specific integrated circuits (ASICs) or field programmable gate arrays (FPGAs). In some embodiments, such integrated circuits execute instructions that are stored on the circuit itself. In other embodiments, processing unit(s) 2204 can execute instructions stored in local storage 2206. Any type of processors in any combination can be included in processing unit(s) 2204.

[0181] Local storage 2206 can include volatile storage media (e.g., conventional DRAM, SRAM, SDRAM, or the like) and / or non-volatile storage media (e.g., magnetic or optical disk, flash memory, or the like). Storage media incorporated in local storage 2206 can be fixed, removable or upgradeable as desired. Local storage 2206 can be physically or logically divided into various subunits such as a system memory, a read-only memory (ROM), and a permanent storage device. The system memory can be a read-and-write memory device or a volatile read- and-write memory, such as dynamic random-access memory. The system memory can store some or all of the instructions and data that processing unit(s) 2204 need at runtime. The ROM can store static data and instructions that are needed by processing unit(s) 2204. The permanent storage device can be a non-volatile read-and-write memory device that can store instructions and data even when module 2202 is powered down. The term “storage medium” as used herein includes any medium in which data can be stored indefinitely (subject to overwriting, electricaldisturbance, power loss, or the like) and does not include carrier waves and transitory electronic signals propagating wirelessly or over wired connections.

[0182] In some embodiments, local storage 2206 can store one or more software programs to be executed by processing unit(s) 2204, such as an operating system and / or programs implementing various server functions or any system or device described herein.

[0183] Software” refers generally to sequences of instructions that, when executed by processing unit(s) 2204 cause server system 2200 (or portions thereof) to perform various operations, thus defining one or more specific machine embodiments that execute and perform the operations of the software programs. The instructions can be stored as firmware residing in read-only memory and / or program code stored in non-volatile storage media that can be read into volatile working memory for execution by processing unit(s) 2204. Software can be implemented as a single program or a collection of separate programs or program modules that interact as desired. From local storage 2206 (or non-local storage described below), processing unit(s) 2204 can retrieve program instructions to execute and data to process in order to execute various operations described above.

[0184] In some server systems 2200, multiple modules 2202 can be interconnected via a bus or other interconnect 2208, forming a local area network that supports communication between modules 2202 and other components of server system 2200. Interconnect 2208 can be implemented using various technologies including server racks, hubs, routers, etc.

[0185] A wide area network (WAN) interface 2210 can provide data communication capability between the local area network (interconnect 2208) and a larger network, such as the Internet. Conventional or other activities technologies can be used, including wired (e.g., Ethernet, IEEE 802.3 standards) and / or wireless technologies (e.g., Wi-Fi, IEEE 802.11 standards).

[0186] In some embodiments, local storage 2206 is intended to provide working memory for processing unit(s) 2204, providing fast access to programs and / or data to be processed whilereducing traffic on interconnect 2208. Storage for larger quantities of data can be provided on the local area network by one or more mass storage subsystems 2212 that can be connected to interconnect 2208. Mass storage subsystem 2212 can be based on magnetic, optical, semiconductor, or other data storage media. Direct attached storage, storage area networks, network- attached storage, and the like can be used. Any data stores or other collections of data described herein as being produced, consumed, or maintained by a service or server can be stored in mass storage subsystem 2212. In some embodiments, additional data storage resources may be accessible via WAN interface 2210 (potentially with increased latency).

[0187] Server system 2200 can operate in response to requests received via WAN interface 2210. For example, one of modules 2202 can implement a supervisory function and assign discrete tasks to other modules 2202 in response to received requests. Conventional work allocation techniques can be used. As requests are processed, results can be returned to the requester via WAN interface 2210. Such operation can generally be automated. Further, in some embodiments, WAN interface 2210 can connect multiple server systems 2200 to each other, providing scalable systems capable of managing high volumes of activity. Conventional or other techniques for managing server systems and server farms (collections of server systems that cooperate) can be used, including dynamic resource allocation and reallocation.

[0188] Server system 2200 can interact with various user-owned or user-operated devices via a wide-area network such as the Internet. An example of a user-operated device is shown in FIG. 22 as client computing system 2214. Client computing system 2214 can be implemented, for example, as a consumer device such as a smartphone, other mobile phone, tablet computer, wearable computing device (e.g., smart watch, eyeglasses), desktop computer, laptop computer, and so on.

[0189] Client computing system 2214 can communicate via WAN interface 2210. Client computing system 2214 can include conventional computer components such as processing unit(s) 2216, storage device 2218, network interface 2220, user input device 2222, and user output device 2224. Client computing system 2214 can be a computing device implemented in avariety of form factors, such as a desktop computer, laptop computer, tablet computer, smartphone, other mobile computing device, wearable computing device, or the like.

[0190] Processor 2216 and storage device 2218 can be similar to processing unit(s) 2204 and local storage 2206 described above. Suitable devices can be selected based on the demands to be placed on client computing system 2214; for example, client computing system 2214 can be implemented as a “thin” client with limited processing capability or as a high-powered computing device. Client computing system 2214 can be provisioned with program code executable by processing unit(s) 2216 to enable various interactions with server system 2200 of a message management service such as accessing messages, performing actions on messages, and other interactions described above. Some client computing systems 2214 can also interact with a messaging service independently of the message management service.

[0191] Network interface 2220 can provide a connection to a wide area network (e.g., the Internet) to which WAN interface 2210 of server system 2200 is also connected. In various embodiments, network interface 2220 can include a wired interface (e.g., Ethernet) and / or a wireless interface implementing various RF data communication standards such as Wi-Fi, Bluetooth, or cellular data network standards (e.g., 3G, 4G, 5G, LTE, etc.).

[0192] User input device 2222 can include any device (or devices) via which a user can provide signals to client computing system 2214; client computing system 2214 can interpret the signals as indicative of particular user requests or information. In various embodiments, user input device 2222 can include any or all of a keyboard, touch pad, touch screen, mouse or other pointing device, scroll wheel, click wheel, dial, button, switch, keypad, microphone, and so on.

[0193] User output device 2224 can include any device via which client computing system 2214 can provide information to a user. For example, user output device 2224 can include a display to display images generated by or delivered to client computing system 2214. The display can incorporate various image generation technologies, e.g., a liquid crystal display (LCD), light-emitting diode (LED) including organic light-emitting diodes (OLED), projectionsystem, cathode ray tube (CRT), or the like, together with supporting electronics (e.g., digital-to- analog or analog-to-digital converters, signal processors, or the like). Some embodiments can include a device such as a touchscreen that function as both input and output device. In some embodiments, other user output devices 2224 can be provided in addition to or instead of a display. Examples include indicator lights, speakers, tactile “display” devices, printers, and so on.

[0194] Some embodiments include electronic components, such as microprocessors, storage and memory that store computer program instructions in a computer readable storage medium. Many of the features described in this specification can be implemented as processes that are specified as a set of program instructions encoded on a computer readable storage medium. When these program instructions are executed by one or more processing units, they cause the processing unit(s) to perform various operation indicated in the program instructions. Examples of program instructions or computer code include machine code, such as is produced by a compiler, and files including higher-level code that are executed by a computer, an electronic component, or a microprocessor using an interpreter. Through suitable programming, processing unit(s) 2204 and 2216 can provide various functionality for server system 2200 and client computing system 2214, including any of the functionality described herein as being performed by a server or client, or other functionality associated with message management services.

[0195] It will be appreciated that server system 2200 and client computing system 2214 are illustrative and that variations and modifications are possible. Computer systems used in connection with embodiments of the present disclosure can have other capabilities not specifically described here. Further, while server system 2200 and client computing system 2214 are described with reference to particular blocks, it is to be understood that these blocks are defined for convenience of description and are not intended to imply a particular physical arrangement of component parts. For instance, different blocks can be but need not be located in the same facility, in the same server rack, or on the same motherboard. Further, the blocks need not correspond to physically distinct components. Blocks can be configured to perform variousoperations, e.g., by programming a processor or providing appropriate control circuitry, and various blocks might or might not be reconfigurable depending on how the initial configuration is obtained. Embodiments of the present disclosure can be realized in a variety of apparatus including electronic devices implemented using any combination of circuitry and software.

[0196] While the disclosure has been described with respect to specific embodiments, one skilled in the art will recognize that numerous modifications are possible. For instance, although specific examples of rules (including triggering conditions and / or resulting actions) and processes for generating suggested rules are described, other rules and processes can be implemented. Embodiments of the disclosure can be realized using a variety of computer systems and communication technologies including but not limited to specific examples described herein.

[0197] Embodiments of the present disclosure can be realized using any combination of dedicated components and / or programmable processors and / or other programmable devices. The various processes described herein can be implemented on the same processor or different processors in any combination. Where components are described as being configured to perform certain operations, such configuration can be accomplished, e.g., by designing electronic circuits to perform the operation, by programming programmable electronic circuits (such as microprocessors) to perform the operation, or any combination thereof. Further, while the embodiments described above may make reference to specific hardware and software components, those skilled in the art will appreciate that different combinations of hardware and / or software components may also be used and that particular operations described as being implemented in hardware might also be implemented in software or vice versa.

[0198] Computer programs incorporating various features of the present disclosure may be encoded and stored on various computer readable storage media; suitable media include magnetic disk or tape, optical storage media such as compact disk (CD) or DVD (digital versatile disk), flash memory, and other non-transitory media. Computer readable media encoded with the program code may be packaged with a compatible electronic device, or the program code may beprovided separately from electronic devices (e.g., via Internet download or as a separately packaged computer-readable storage medium).

[0199] Thus, although the disclosure has been described with respect to specific embodiments, it will be appreciated that the disclosure is intended to cover all modifications and equivalents within the scope of the following claims.

[0200] As utilized herein, the terms “approximately,” “about,” “substantially”, and similar terms are intended to have a broad meaning in harmony with the common and accepted usage by those of ordinary skill in the art to which the subject matter of this disclosure pertains. It should be understood by those of skill in the art who review this disclosure that these terms are intended to allow a description of certain features described and claimed without restricting the scope of these features to the precise numerical ranges provided. Accordingly, these terms should be interpreted as indicating that insubstantial or inconsequential modifications or alterations of the subject matter described and claimed are considered to be within the scope of the disclosure as recited in the appended claims. In some examples, these terms allow for a plus- or-minus deviation of 10 percent.

[0201] It should be noted that the terms “exemplary,” “example,” “potential,” and variations thereof, as used herein to describe various embodiments, are intended to indicate that such embodiments are possible examples, representations, or illustrations of possible embodiments (and such terms are not intended to connote that such embodiments are necessarily extraordinary or superlative examples).

[0202] The term “coupled” and variations thereof, as used herein, means the joining of two members directly or indirectly to one another. Such joining may be stationary (e.g., permanent or fixed) or moveable (e.g., removable or releasable). Such joining may be achieved with the two members coupled directly to each other, with the two members coupled to each other using a separate intervening member and any additional intermediate members coupled with one another, or with the two members coupled to each other using an intervening memberthat is integrally formed as a single unitary body with one of the two members. If “coupled” or variations thereof are modified by an additional term (e.g., directly coupled), the generic definition of “coupled” provided above is modified by the plain language meaning of the additional term (e.g., “directly coupled” means the joining of two members without any separate intervening member), resulting in a narrower definition than the generic definition of “coupled” provided above. Such coupling may be mechanical, electrical, or fluidic.

[0203] The term “or,” as used herein, is used in its inclusive sense (and not in its exclusive sense) so that when used to connect a list of elements, the term “or” means one, some, or all of the elements in the list. Conjunctive language such as the phrase “at least one of X, Y, and Z,” unless specifically stated otherwise, is understood to convey that an element may be either X, Y, Z; X and Y ; X and Z; Y and Z; or X, Y, and Z (i.e., any combination of X, Y, and Z). Thus, such conjunctive language is not generally intended to imply that certain embodiments require at least one of X, at least one of Y, and at least one of Z to each be present, unless otherwise indicated.

[0204] References herein to the positions of elements (e.g., “top,” “bottom,” “above,” “below”) are merely used to describe the orientation of various elements in the Figures. It should be noted that the orientation of various elements may differ according to other exemplary embodiments, and that such variations are intended to be encompassed by the present disclosure.

[0205] The embodiments described herein have been described with reference to drawings. The drawings illustrate certain details of specific embodiments that implement the systems, methods and programs described herein. However, describing the embodiments with drawings should not be construed as imposing on the disclosure any limitations that may be present in the drawings.

[0206] It is important to note that the construction and arrangement of the devices, assemblies, and steps as shown in the various exemplary embodiments is illustrative only. Additionally, any element disclosed in one embodiment may be incorporated or utilized with anyother embodiment disclosed herein. Although only one example of an element from one embodiment that can be incorporated or utilized in another embodiment has been described above, it should be appreciated that other elements of the various embodiments may be incorporated or utilized with any of the other embodiments disclosed herein.

[0207] The foregoing description of embodiments has been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the disclosure to the precise form disclosed, and modifications and variations are possible in light of the above teachings or may be acquired from this disclosure. The embodiments were chosen and described in order to explain the principles of the disclosure and its practical application to enable one skilled in the ail to utilize the various embodiments and with various modifications as are suited to the particular use contemplated. Other substitutions, modifications, changes and omissions may be made in the design, operating conditions and arrangement of the embodiments without departing from the scope of the present disclosure as expressed in the appended claims.WORKING EXAMPLE

[0208] Example 1: Exemplary Identification of Candidate Methylation Biomarkers for CRC Detection

[0209] The various methods and their embodiments disclosed herein can be used to detect the presence of a certain phenotype, such as a disease or cancer, in a subject. For example, various embodiments seek to identify sets of DMRs for detecting a phenotype by methylation sequencing of converted DNA from phenotypic samples (e.g. formalin-fixed paraffin-embedded (FFPE) tumor specimens or circulating tumor DNA (ctDNA) samples) and converted gDNA or cfDNA from healthy / normal samples. An example experimental design may involve use of deep, whole genome or panel-based sequencing on DNA from healthy / normal samples (e.g., gDNA or cfDNA from normal tissues or healthy individuals) and from phenotypic samples (e.g., DNA from tumor biopsies or ctDNA from cancer patients) following conversion of unmethylated cytosine (C) in CpG di-nucleotides to uracil (U). In someembodiments, methylome sequencing data of cfDNA from healthy individuals are compared to methylome sequencing data of DNA from tumor biopsies. In some embodiments, methylome sequencing data of DNA from tumor biopsies are compared to methylome sequencing data of DNA from adjacent normal tissues.

[0210] In one example embodiment, deep whole genome methylation sequencing was conducted on converted DNA samples from 100 healthy individuals (median effective coverage of 352x±38x) and from tumor specimens of 75 CRC patients (median effective coverage of 48x±18x). An exemplary experimental workflow is shown in Fig. 3 A. DNA was extracted from samples sourced from 100 healthy individuals and 75 patients with CRC. Following library preparation, sequencing was conducted on converted DNA. Reads were mapped and aligned to a reference genome.

[0211] As shown in FIG. 3B, the two cohorts were chosen to be balanced in terms of age (CRC: 58+11 years; healthy: 57+8 years) and to represent major ethnicities in the USA, and the CRC cohort was chosen to represent all stages, histologies and morphologies, and micro satellite instability (MSI, 23%). FIG. 3B shows histograms of age distribution among healthy individuals and CRC patients (left), self-reported ethnicity among healthy individuals and CRC patients (middle), and proportion of CRC patients by stage, further stratified by microsatellite status (right). FIG. 4 depicts the cohort level distributions of effective coverage, methylation levels, and protection rates. Differentially methylated genomic patterns were defined between patients with CRC and healthy individuals by utilizing patterns of co-methylation of adjacent CpG loci. These differential methylation profiles are strong biomarkers for targeted sequencing panels for early cancer detection.

[0212] In the exemplary embodiment, individualized sample-level methylomes were created and combined with hgl9 reference using the methods disclosed herein, which resulted in 5 IM total CpGs. Any CpG available in less than 25% of total samples were removed, resulting in 28.5M CpGs. FIG. 5 shows the CpG distribution per cohort. The number of CpGs covered is plotted against the fraction of samples in each group covering those CpGs.

[0213] Using the combined methylome and a threshold of lOObp, 8. IM ridges were found using the preliminary segmentation methods disclosed herein. The ridges were filtered to autosomes only, and to regions that contain at least 5 CpGs at a density of at least 0.03 cpg / bp, which resulted in 482K ridges containing 8.26M CpGs and 147.5Mbp. The distribution of these ridges is shown in FIG. 6. Table P02 discloses ridges (chr 21, 22) generated by the preliminary segmentation described herein.

[0214] Further segmentation was then performed using a machine learning model as described herein to identify regions differentially methylated between the healthy and CRC cohorts as well as between subpopulations within the CRC cohort, including age, sex, ethnicity, stage, histology, and microsatellite instability (MSI) vs microsatellite stability (MSS). FIG. 9 illustrates such a segmentation procedure. For a given region, the methylation load of the healthy and CRC cohorts were plotted (top), and the segmentation procedure identifies and calculates the differential methylation load between the region (bottom). The horizontal bars in the lower panel show the differential methylation load. Table P05 discloses DMRs generated by the segmentation / modeling described herein.

[0215] Candidate biomarkers are scored and prioritized using methods disclosed herein. FIG. 10 shows differential methylation score and CpG density distribution of biomarker candidates. FIG. 11 shows number of biomarker candidates and the differential methylation score cutoff based on a preset 2Mbp total panel size or number of biomarkers (top), and CpG density, length, and methylation load distribution of biomarker candidates (bottom). Table P04 discloses CRC methylation biomarkers (chr 21, 22) generated by the scoring / prioritization described herein.

[0216] Using the methods disclosed herein, 184,265 differentially methylated regions between healthy and CRC cohorts, spanning more than 1.71 million CpGs and more than 18.76 Mbp, were discovered. 76% of all discovered regions in the example embodiment were hypermethylated (70% CpG islands, 1.3% CpG shelves, 21% CpG shores) and the rest werehypomethylated (7.3% CpG islands, 8.6% CpG shelves, 25% CpG shores). FIGs. 20 and 21 show the density distributions of the biomarkers selected using the methods described herein.

[0217] Based on deep whole genome methylation sequencing data from heterogeneous cohorts (see Fig. 3), representative of the US population eligible for CRC screening, the example embodiment identified many differentially methylated regions as strong biomarker candidates for the early detection of cancer (see Fig. 20). Compared to recurrently mutated driver genes in CRC, it was found that differential methylation profiles of CRC samples are generally much more homogenous and are therefore ideal biomarkers for targeted sequencing panels with the purpose of early cancer detection. Further, analysis of these patterns based on clinicopathologic factors enabled discovery of subtype specific markers (see Fig. 21), which can be incorporated to ensure equivalent performance for underrepresented subtypes or subpopulations.* * * *

[0218] TABLE_P02 chrom start end name nCpGs length density chr21 9421448 9421718 chr21 ridge 31 14 14 270 0.05185185185185185 chr21 42838002 42838447 chr21_ridge_92606_18 18 445 0.04044943820224719 chr21 42833215 42833363 chr21_ridge_92590_6 6 148 0 . 04054054054054054 chr21 42830321 42830952 chr21_ridge_92584_29 29 631 0.04595879556259905 chr21 42829926 42830116 chr21_ridge_92582_8 8 190 0 . 042105263157894736 chr21 42820423 42820795 chr21_ridge_92550_18 18 372 0.04838709677419355 chr21 42812889 42813118 chr21_ridge_92525_ll 11 229 0 . 048034934497816595 chr21 42807804 42807955 chr21_ridge_92510_10 10 151 0.06622516556291391 chr21 42802332 42802420 chr21_ridge_92488_5 5 88 0 . 056818181818181816 chr21 42800384 42800555 chr21_ridge_92482_8 8 171 0.04678362573099415 chr21 42799699 42799935 chr21_ridge_92480_10 10 236 0.0423728813559322 chr21 42797842 42799200 chr21_ridge_92477_109 109 1358 0.08026509572901326 chr21 42797066 42797187 chr21_ridge_92475_5 5 121 0.04132231404958678 chr21 42791865 42793664 chr21_ridge_92467_76 76 1799 0 . 042245692051139525 chr21 42790513 42790562 chr21_ridge_92462_5 5 49 0.10204081632653061 chr21 42779742 42780231 chr21_ridge_92426_21 21 489 0.04294478527607362 chr21 42778795 42778950 chr21_ridge_92422_7 7 155 0.04516129032258064 chr21 42777825 42777957 chr21_ridge_92419_6 6 132 0 . 045454545454545456 chr21 42776971 42777134 chr21_ridge_92416_7 7 163 0.04294478527607362 chr21 42770789 42771195 chr21_ridge_92398_17 17 406 0.04187192118226601 chr21 42768113 42768167 chr21_ridge_92389_6 6 54 0.1111111111111111 chr21 42754342 42754482 chr21_ridge_92349_6 6 140 0.04285714285714286 chr21 42753336 42753645 chr21_ridge_92347_14 14 309 0.045307443365695796 chr21 42751843 42752133 chr21_ridge_92341_12 12 290 0.041379310344827586 chr21 42838550 42838629 chr21_ridge_92607_5 5 79 0.06329113924050633 chr21 42840046 42840218 chr21_ridge_92611_7 7 172 0 . 040697674418604654 chr21 42841545 42841686 chr21_ridge_92613_6 6 141 0.0425531914893617 chr21 42842953 42843049 chr21_ridge_92620_5 5 96 0.052083333333333336 chr21 42914440 42914580 chr21_ridge_92830_6 6 140 0.04285714285714286 chr21 42911911 42912023 chr21 ridge 92822 8 8 112 0.07142857142857142 chr21 42911680 42911775 chr21_ridge_92821_5 5 95 0.05263157894736842 chr21 42909859 42910146 chr21_ridge_92816_12 12 287 0 . 041811846689895474 chr21 42909608 42909702 chr21_ridge_92815_5 5 94 0.05319148936170213 chr21 42902756 42902782 chr21_ridge_92796_5 5 26 0.19230769230769232 chr21 42902514 42902624 chr21_ridge_92795_5 5 110 0 . 045454545454545456 chr21 42900983 42901138 chr21_ridge_92792_8 8 155 0.05161290322580645 chr21 42898703 42898872 chr21_ridge_92786_8 8 169 0 . 047337278106508875 chr21 42898199 42898313 chr21_ridge_92784_6 6 114 0.05263157894736842 chr21 42897091 42897172 chr21_ridge_92780_7 7 81 0.08641975308641975 chr21 42749631 42750125 chr21_ridge_92336_20 20 494 0.04048582995951417 chr21 42896453 42896926 chr21_ridge_92779_20 20 473 0.042283298097251586 chr21 42880998 42881206 chr21_ridge_92723_9 9 208 0.04326923076923077 chr21 42878724 42880797 chr21_ridge_92722_173 173 2073 0.08345393150024119 chr21 42868801 42869058 chr21_ridge_92694_ll 11 257 0 . 042801556420233464 chr21 42868058 42868159 chr21_ridge_92691_5 5 101 0.04950495049504951 chr21 42867406 42867548 chr21_ridge_92689_10 10 142 0.07042253521126761 chr21 42865986 42866455 chr21_ridge_92686_24 24 469 0.0511727078891258 chr21 42855285 42855518 chr21_ridge_92651_ll 11 233 0.04721030042918455 chr21 42852313 42852961 chr21_ridge_92642_27 27 648 0 . 041666666666666664 chr21 42851282 42851425 chr21_ridge_92639_6 6 143 0.04195804195804196 chr21 42849100 42849341 chr21_ridge_92635_12 12 241 0.04979253112033195 chr21 42844539 42845489 chr21_ridge_92624_39 39 950 0.04105263157894737 chr21 42896079 42896352 chr21 ridge 92778 16 16 273 0.05860805860805861 chr21 42741184 42742535 chr21_ridge_92310_58 58 1351 0.04293116210214656 chr21 42736376 42736490 chr21_ridge_92296_6 6 114 0.05263157894736842 chr21 42735080 42735156 chr21_ridge_92291_5 5 76 0.06578947368421052 chr21 42632583 42632769 chr21_ridge_91970_8 8 186 0 . 043010752688172046 chr21 42628965 42629285 chr21_ridge_91959_18 18 320 0.05625 chr21 42627423 42627562 chr21_ridge_91952_6 6 139 0.04316546762589928 chr21 42626790 42626940 chr21_ridge_91950_7 7 150 0 . 04666666666666667 chr21 42624691 42624903 chr21_ridge_91944_12 12 212 0.05660377358490566 chr21 42623850 42623935 chr21_ridge_91941_5 5 85 0 . 058823529411764705Chr21 42620640 42620776 chr21_ridge_91935_9 9 136 0.0661764705882353 chr21 42618753 42620516 chr21 ridge 91934 76 76 1763 0.04310833806012479 chr21 42617816 42618087 chr21_ridge_91931_18 18 271 0.06642066420664207 chr21 42614794 42615185 chr21_ridge_91921_17 17 391 0.043478260869565216 chr21 42614084 42614182 chr21_ridge_91919_5 5 98 0.05102040816326531 chr21 42639949 42640041 chr21_ridge_91994_5 5 92 0.05434782608695652 chr21 42613665 42613979 chr21_ridge_91918_13 13 314 0.041401273885350316 chr21 42610006 42610118 chr21_ridge_91906_6 6 112 0.05357142857142857 chr21 42608310 42608493 chr21_ridge_91901_9 9 183 0.04918032786885246 chr21 42604824 42605046 chr21_ridge_91888_ll 11 222 0.04954954954954955 chr21 42604049 42604229 chr21_ridge_91886_ll 11 180 0.06111111111111111 chr21 42600093 42600189 chr21_ridge_91874_5 5 96 0.052083333333333336 chr21 42598202 42598315 chr21_ridge_91868_7 7 113 0.061946902654867256 chr21 42597781 42597905 chr21_ridge_91866_5 5 124 0.04032258064516129 chr21 42596834 42597147 chr21_ridge_91862_17 17 313 0.054313099041533544 chr21 42595387 42595531 chr21_ridge_91858_6 6 144 0.041666666666666664 chr21 42594439 42594541 chr21_ridge_91855_5 5 102 0.049019607843137254 chr21 42588478 42589241 chr21_ridge_91841_33 33 763 0.04325032765399738 chr21 42610322 42610443 chr21_ridge_91907_5 5 121 0.04132231404958678 chr21 42914739 42914889 chr21_ridge_92831_6 6 150 0.04 chr21 42646990 42647142 chr21_ridge_92017_7 7 152 0.046052631578947366 chr21 42648634 42648703 chr21_ridge_92022_6 6 69 0.08695652173913043 chr21 42731461 42731551 chr21_ridge_92284_5 5 90 0.05555555555555555 chr21 42731085 42731327 chr21_ridge_92283_10 10 242 0.04132231404958678 chr21 42722857 42722957 chr21 ridge 92254 8 8 100 0.08 chr21 42722027 42722250 chr21_ridge_92252_10 10 223 0.04484304932735426 chr21 42716865 42717002 chr21_ridge_92238_6 6 137 0.043795620437956206 chr21 42716249 42716434 chr21_ridge_92235_10 10 185 0.05405405405405406 chr21 42698432 42698634 chr21_ridge_92179_10 10 202 0.04950495049504951 chr21 42697727 42697838 chr21_ridge_92176_6 6 111 0.05405405405405406 chr21 42693528 42693777 chr21 ridge 92166 10 10 249 0.040160642570281124 chr21 42692728 42692862 chr21_ridge_92164_6 6 134 0.04477611940298507 chr21 42690219 42690392 chr21_ridge_92154_10 10 173 0.057803468208092484 chr21 42647253 42647656 chr21_ridge_92018_18 18 403 0.04466501240694789 chr21 42688463 42689901 chr21_ridge_92152_83 83 1438 0.057719054242002785 chr21 42687445 42687564 chr21_ridge_92149_6 6 119 0.05042016806722689 chr21 42686832 42686975 chr21_ridge_92147_6 6 143 0.04195804195804196 chr21 42676907 42677014 chr21_ridge_92112_6 6 107 0.056074766355140186 chr21 42675619 42676782 chr21_ridge_92111_63 63 1163 0.05417024935511608 chr21 42664943 42665110 chr21_ridge_92076_7 7 167 0.041916167664670656 chr21 42662182 42662686 chr21_ridge_92066_25 25 504 0.0496031746031746 chr21 42661252 42661635 chr21_ridge_92063_16 16 383 0.04177545691906005 chr21 42655284 42655401 chr21_ridge_92045_6 6 117 0.05128205128205128 chr21 42652829 42653014 chr21_ridge_92032_8 8 185 0.043243243243243246 chr21 42651652 42651919 chr21_ridge_92030_ll 11 267 0.04119850187265917 chr21 42649079 42649202 chr21_ridge_92024_6 6 123 0.04878048780487805 chr21 42688161 42688352 chr21_ridge_92151_8 8 191 0.041884816753926704 chr21 42915002 42915099 chr21 ridge 92832 5 5 97 0.05154639175257732 chr21 42919542 42919740 chr21_ridge_92849_8 8 198 0.04040404040404041 chr21 42925213 42925477 chr21_ridge_92866_14 14 264 0.05303030303030303 chr21 43154736 43154923 chr21_ridge_93388_8 8 187 0.0427807486631016 chr21 43150678 43150850 chr21_ridge_93378_7 7 172 0.040697674418604654 chr21 43150251 43150360 chr21_ridge_93376_6 6 109 0.05504587155963303 chr21 43146988 43147352 chr21 ridge 93368 15 15 364 0.04120879120879121 chr21 43145493 43146565 chr21_ridge_93366_54 54 1072 0.05037313432835821 chr21 43144853 43144952 chr21_ridge_93364_5 5 99 0.050505050505050504 chr21 43144051 43144198 chr21_ridge_93361_8 8 147 0.05442176870748299 chr21 43143318 43143738 chr21_ridge_93359_21 21 420 0.05 chr21 43132387 43132488 chr21_ridge_93325_10 10 101 0.09900990099009901 chr21 43131446 43131562 chr21_ridge_93322_6 6 116 0.05172413793103448 chr21 43126226 43126394 chr21_ridge_93305_7 7 168 0.041666666666666664 chr21 43155709 43155829 chr21_ridge_93392_5 5 120 0.041666666666666664 chr21 43125867 43125993 chr21_ridge_93304_7 7 126 0.05555555555555555Chr21 43119246 43119363 chr21_ridge_93280_5 5 117 0.042735042735042736 chr21 43118374 43118552 chr21 ridge 93277 10 10 178 0.056179775280898875 chr21 43118025 43118148 chr21_ridge_93275_7 7 123 0.056910569105691054 chr21 43117573 43117734 chr21_ridge_93273_10 10 161 0.062111801242236024 chr21 43117243 43117336 chr21_ridge_93271_5 5 93 0.053763440860215055 chr21 43109209 43109723 chr21_ridge_93249_39 39 514 0.07587548638132295 chr21 43108577 43108975 chr21_ridge_93248_16 16 398 0.04020100502512563 chr21 43108211 43108449 chr21_ridge_93247_10 10 238 0.04201680672268908 chr21 43106803 43107007 chr21_ridge_93243_9 9 204 0.04411764705882353 chr21 43105117 43105422 chr21_ridge_93237_13 13 305 0.04262295081967213 chr21 43104947 43105008 chr21_ridge_93236_5 5 61 0.08196721311475409 chr21 43122379 43122495 chr21_ridge_93290_5 5 116 0.04310344827586207 chr21 43103917 43104162 chr21_ridge_93233_10 10 245 0.04081632653061224 chr21 43160574 43162416 chr21_ridge_93407_118 118 1842 0.06406080347448426 chr21 43163866 43165456 chr21_ridge_93410_72 72 1590 0.045283018867924525 chr21 43213294 43213615 chr21_ridge_93538_14 14 321 0.04361370716510903 chr21 43199788 43199972 chr21_ridge_93494_8 8 184 0.043478260869565216 chr21 43199494 43199636 chr21_ridge_93493_8 8 142 0.056338028169014086 chr21 43198114 43198830 chr21_ridge_93491_45 45 716 0.06284916201117319 chr21 43196076 43196530 chr21_ridge_93484_19 19 454 0.04185022026431718 chr21 43191889 43192088 chr21_ridge_93472_8 8 199 0.04020100502512563 chr21 43191430 43191752 chr21_ridge_93471_13 13 322 0.040372670807453416 chr21 43189372 43189563 chr21_ridge_93462_10 10 191 0.05235602094240838 chr21 43188982 43189266 chr21_ridge_93461_13 13 284 0.045774647887323945 chr21 43188107 43188532 chr21 ridge 93459 23 23 425 0.05411764705882353 chr21 43186095 43187482 chr21_ridge_93457_140 140 1387 0.10093727469358327 chr21 43163608 43163730 chr21_ridge_93409_ll 11 122 0.09016393442622951 chr21 43183570 43184052 chr21_ridge_93450_21 21 482 0.043568464730290454 chr21 43180654 43180748 chr21_ridge_93445_6 6 94 0.06382978723404255 chr21 43179083 43179136 chr21_ridge_93439_5 5 53 0.09433962264150944 chr21 43177880 43178137 chr21 ridge 93436 11 11 257 0.042801556420233464 chr21 43172946 43173035 chr21_ridge_93426_6 6 89 0.06741573033707865 chr21 43172555 43172834 chr21_ridge_93425_13 13 279 0.04659498207885305 chr21 43171240 43171426 chr21_ridge_93423_9 9 186 0.04838709677419355 chr21 43171087 43171138 chr21_ridge_93422_6 6 51 0.11764705882352941 chr21 43170866 43170986 chr21_ridge_93421_5 5 120 0.041666666666666664 chr21 43170348 43170446 chr21_ridge_93419_5 5 98 0.05102040816326531 chr21 43168053 43168495 chr21_ridge_93414_19 19 442 0.042986425339366516 chr21 43165571 43167145 chr21_ridge_93411_70 70 1574 0.044472681067344345 chr21 43182958 43183466 chr21_ridge_93449_23 23 508 0.045275590551181105 chr21 42585943 42586005 chr21_ridge_91833_5 5 62 0.08064516129032258 chr21 43101105 43102000 chr21_ridge_93228_41 41 895 0.04581005586592179 chr21 43094327 43094500 chr21_ridge_93210_7 7 173 0.04046242774566474 chr21 43042819 43043483 chr21_ridge_93053_27 27 664 0.04066265060240964 chr21 43041843 43042203 chr21_ridge_93051_17 17 360 0.04722222222222222 chr21 43040179 43040280 chr21_ridge_93046_6 6 101 0.0594059405940594 chr21 43039826 43039991 chr21_ridge_93045_8 8 165 0.048484848484848485 chr21 43038850 43038990 chr21 ridge 93040 7 7 140 0.05 chr21 43036318 43036341 chr21_ridge_93034_5 5 23 0.21739130434782608 chr21 43030964 43031315 chr21_ridge_93023_17 17 351 0.04843304843304843 chr21 43029604 43029811 chr21_ridge_93020_9 9 207 0.043478260869565216 chr21 43027473 43027598 chr21_ridge_93014_6 6 125 0.048 chr21 43020930 43021213 chr21_ridge_93001_13 13 283 0.045936395759717315 chr21 43013547 43013735 chr21 ridge 92981 8 8 188 0.0425531914893617 chr21 43043589 43043727 chr21_ridge_93054_6 6 138 0.043478260869565216 chr21 43012766 43012990 chr21_ridge_92978_9 9 224 0.04017857142857143 chr21 42955392 42955544 chr21_ridge_92956_7 7 152 0.046052631578947366 chr21 42953895 42954033 chr21_ridge_92952_8 8 138 0.057971014492753624 chr21 42953288 42953748 chr21_ridge_92951_22 22 460 0.04782608695652174 chr21 42939844 42940427 chr21_ridge_92912_25 25 583 0.04288164665523156 chr21 42939194 42939259 chr21_ridge_92910_5 5 65 0.07692307692307693 chr21 42937639 42937876 chr21_ridge_92905_12 12 237 0.05063291139240506 chr21 42936039 42936148 chr21_ridge_92901_5 5 109 0.045871559633027525Chr21 42935459 42935761 chr21_ridge_92899_14 14 302 0.046357615894039736 chr21 42934045 42934532 chr21 ridge 92896 21 21 487 0.043121149897330596 chr21 42926118 42926399 chr21_ridge_92869_24 24 281 0.08540925266903915 chr21 42925590 42925728 chr21_ridge_92867_8 8 138 0 . 057971014492753624 chr21 43010809 43011091 chr21_ridge_92973_12 12 282 0.0425531914893617 chr21 43094728 43094836 chr21_ridge_93212_5 5 108 0 . 046296296296296294 chr21 43043885 43043947 chr21_ridge_93055_5 5 62 0.08064516129032258 chr21 43051039 43051570 chr21_ridge_93077_23 23 531 0.04331450094161959 chr21 43093082 43093611 chr21_ridge_93207_24 24 529 0 . 045368620037807186 chr21 43092405 43092724 chr21_ridge_93206_16 16 319 0 . 050156739811912224 chr21 43091969 43092201 chr21_ridge_93204_10 10 232 0.04310344827586207 chr21 43090728 43090837 chr21_ridge_93200_7 7 109 0.06422018348623854 chr21 43090290 43090626 chr21_ridge_93199_20 20 336 0.05952380952380952 chr21 43085609 43085967 chr21_ridge_93187_15 15 358 0.04189944134078212 chr21 43084669 43084828 chr21_ridge_93185_9 9 159 0.05660377358490566 chr21 43083023 43083230 chr21_ridge_93180_10 10 207 0.04830917874396135 chr21 43081907 43082121 chr21_ridge_93177_10 10 214 0.04672897196261682 chr21 43081125 43081276 chr21_ridge_93174_8 8 151 0.052980132450331126 chr21 43080082 43080213 chr21_ridge_93172_6 6 131 0.04580152671755725 chr21 43047048 43047203 chr21_ridge_93065_7 7 155 0.04516129032258064 chr21 43077052 43077197 chr21_ridge_93162_7 7 145 0.04827586206896552 chr21 43072592 43072732 chr21_ridge_93147_6 6 140 0.04285714285714286 chr21 43071621 43071777 chr21_ridge_93143_9 9 156 0 . 057692307692307696 chr21 43070973 43071493 chr21_ridge_93142_23 23 520 0.04423076923076923 chr21 43070457 43070559 chr21_ridge_93140_5 5 102 0.049019607843137254 chr21 43069831 43070268 chr21_ridge_93139_21 21 437 0.04805491990846682 chr21 43068806 43068974 chr21_ridge_93135_8 8 168 0 . 047619047619047616 chr21 43063811 43063909 chr21_ridge_93117_6 6 98 0 . 061224489795918366 chr21 43062159 43062373 chr21_ridge_93111_ll 11 214 0.0514018691588785 chr21 43060277 43060391 chr21_ridge_93104_5 5 114 0.043859649122807015 chr21 43059508 43059730 chr21 ridge 93101 10 10 222 0.04504504504504504 chr21 43057765 43057936 chr21_ridge_93097_7 7 171 0.04093567251461988 chr21 43076816 43076878 chr21_ridge_93161_5 5 62 0.08064516129032258 chr21 43214721 43214998 chr21_ridge_93543_12 12 277 0.04332129963898917 chr21 42585427 42585737 chr21_ridge_91832_13 13 310 0 . 041935483870967745 chr21 42572670 42572828 chr21_ridge_91788_8 8 158 0.05063291139240506 chr21 41860099 41860298 chr21_ridge_89487_8 8 199 0.04020100502512563 chr21 41859217 41859299 chr21_ridge_89483_5 5 82 0.06097560975609756 chr21 41857188 41857492 chr21_ridge_89478_25 25 304 0.08223684210526316 chr21 41853726 41853982 chr21_ridge_89465_ll 11 256 0.04296875 chr21 41853136 41853367 chr21_ridge_89463_ll 11 231 0 . 047619047619047616 chr21 41846690 41846916 chr21_ridge_89446_12 12 226 0.05309734513274336 chr21 41846466 41846588 chr21_ridge_89445_6 6 122 0.04918032786885246 chr21 41837448 41837523 chr21_ridge_89408_7 7 75 0.09333333333333334 chr21 41827146 41827264 chr21_ridge_89378_5 5 118 0.0423728813559322 chr21 41814475 41814736 chr21_ridge_89339_13 13 261 0.04980842911877394 chr21 41808610 41808676 chr21_ridge_89318_5 5 66 0.07575757575757576 chr21 41806975 41807173 chr21 ridge 89314 8 8 198 0 . 04040404040404041 chr21 41801252 41801350 chr21_ridge_89295_5 5 98 0.05102040816326531 chr21 41798306 41798431 chr21_ridge_89283_5 5 125 0.04 chr21 41797496 41797589 chr21_ridge_89280_5 5 93 0 . 053763440860215055 chr21 41797279 41797395 chr21_ridge_89279_6 6 116 0.05172413793103448 chr21 41796350 41796455 chr21_ridge_89275_5 5 105 0 . 047619047619047616 chr21 41794423 41794563 chr21 ridge 89269 6 6 140 0.04285714285714286 chr21 41793191 41793290 chr21_ridge_89265_5 5 99 0.050505050505050504 chr21 41774015 41774291 chr21_ridge_89210_17 17 276 0.06159420289855073 chr21 41768215 41768340 chr21_ridge_89191_5 5 125 0.04 chr21 41764404 41764623 chr21_ridge_89180_10 10 219 0.045662100456621 chr21 41763813 41763923 chr21_ridge_89178_6 6 110 0.05454545454545454 chr21 41861365 41861696 chr21_ridge_89491_26 26 331 0.07854984894259819 chr21 41871925 41872079 chr21_ridge_89520_8 8 154 0.05194805194805195 chr21 41883634 41883896 chr21_ridge_89556_19 19 262 0.07251908396946564 chr21 41884581 41884791 chr21_ridge_89559_12 12 210 0.05714285714285714Chr21 41983017 41983134 chr21_ridge_89875_9 9 117 0.07692307692307693 chr21 41981169 41981279 chr21 ridge 89869 5 5 110 0 . 045454545454545456 chr21 41961224 41961331 chr21_ridge_89808_5 5 107 0.04672897196261682 chr21 41957261 41957341 chr21_ridge_89792_7 7 80 0.0875 chr21 41956361 41956477 chr21_ridge_89788_7 7 116 0.0603448275862069 chr21 41955256 41955375 chr21_ridge_89783_6 6 119 0.05042016806722689 chr21 41952037 41952332 chr21_ridge_89770_13 13 295 0.04406779661016949 chr21 41949750 41949806 chr21_ridge_89761_5 5 56 0.08928571428571429 chr21 41949198 41949575 chr21_ridge_89760_25 25 377 0.06631299734748011 chr21 41945006 41945243 chr21_ridge_89747_13 13 237 0.05485232067510549 chr21 41944522 41944578 chr21_ridge_89746_5 5 56 0.08928571428571429 chr21 41758257 41758728 chr21_ridge_89160_23 23 471 0.04883227176220807 chr21 41939923 41940021 chr21_ridge_89734_5 5 98 0.05102040816326531 chr21 41934808 41934960 chr21_ridge_89718_7 7 152 0.046052631578947366 chr21 41932304 41932465 chr21_ridge_89710_9 9 161 0 . 055900621118012424 chr21 41931584 41932067 chr21_ridge_89709_20 20 483 0 . 041407867494824016 chr21 41931105 41931380 chr21_ridge_89708_19 19 275 0.06909090909090909 chr21 41930137 41930353 chr21_ridge_89705_10 10 216 0 . 046296296296296294 chr21 41908316 41908810 chr21_ridge_89639_21 21 494 0.04251012145748988 chr21 41904761 41904948 chr21_ridge_89629_8 8 187 0.0427807486631016 chr21 41902920 41903067 chr21_ridge_89623_6 6 147 0.04081632653061224 chr21 41895263 41895478 chr21_ridge_89595_12 12 215 0.05581395348837209 chr21 41888444 41888662 chr21_ridge_89573_ll 11 218 0.05045871559633028 chr21 41884901 41885212 chr21_ridge_89560_15 15 311 0.04823151125401929 chr21 41935874 41935986 chr21 ridge 89719 5 5 112 0 . 044642857142857144 chr21 41756424 41756673 chr21_ridge_89155_ll 11 249 0.04417670682730924 chr21 41755051 41755179 chr21_ridge_89149_8 8 128 0.0625 chr21 41752546 41753148 chr21_ridge_89142_29 29 602 0.04817275747508306 chr21 41593654 41593789 chr21_ridge_88604_6 6 135 0 . 044444444444444446 chr21 41586882 41587147 chr21_ridge_88582_22 22 265 0.0830188679245283 chr21 41571574 41571714 chr21 ridge 88528 8 8 140 0.05714285714285714 chr21 41569066 41569336 chr21_ridge_88520_13 13 270 0 . 04814814814814815 chr21 41561019 41561158 chr21_ridge_88485_7 7 139 0.050359712230215826 chr21 41559080 41559274 chr21_ridge_88477_9 9 194 0.04639175257731959 chr21 41554786 41555194 chr21_ridge_88465_19 19 408 0.04656862745098039 chr21 41554390 41554681 chr21_ridge_88464_16 16 291 0.054982817869415807 chr21 41546710 41546818 chr21_ridge_88440_6 6 108 0.05555555555555555 chr21 41541992 41542211 chr21_ridge_88425_ll 11 219 0.0502283105022831 chr21 41539249 41539343 chr21_ridge_88415_6 6 94 0.06382978723404255 chr21 41598371 41598456 chr21_ridge_88623_5 5 85 0 . 058823529411764705 chr21 41538191 41538322 chr21_ridge_88410_8 8 131 0 . 061068702290076333 chr21 41532715 41532827 chr21_ridge_88391_5 5 112 0 . 044642857142857144 chr21 41518186 41518375 chr21_ridge_88342_9 9 189 0 . 047619047619047616 chr21 41516236 41517206 chr21_ridge_88339_47 47 970 0 . 04845360824742268 chr21 41515222 41515712 chr21_ridge_88336_27 27 490 0.05510204081632653 chr21 41514260 41514385 chr21_ridge_88331_5 5 125 0.04 chr21 41512746 41512863 chr21_ridge_88327_5 5 117 0.042735042735042736 chr21 41511947 41512187 chr21 ridge 88325 10 10 240 0 . 041666666666666664 chr21 41508822 41509104 chr21_ridge_88315_16 16 282 0.05673758865248227 chr21 41505761 41505883 chr21_ridge_88305_7 7 122 0.05737704918032787 chr21 41502851 41502934 chr21_ridge_88295_6 6 83 0.07228915662650602 chr21 41496043 41496380 chr21_ridge_88269_16 16 337 0 . 04747774480712166 chr21 41537686 41538020 chr21_ridge_88409_14 14 334 0 . 041916167664670656 chr21 41986626 41986747 chr21 ridge 89886 6 6 121 0.049586776859504134 chr21 41610396 41610519 chr21_ridge_88661_5 5 123 0 . 04065040650406504 chr21 41616290 41616379 chr21_ridge_88681_5 5 89 0 . 056179775280898875 chr21 41750388 41750815 chr21_ridge_89135_27 27 427 0.06323185011709602 chr21 41749246 41749348 chr21_ridge_89130_5 5 102 0 . 049019607843137254 chr21 41748435 41748575 chr21_ridge_89126_7 7 140 0.05 chr21 41748114 41748196 chr21_ridge_89125_5 5 82 0.06097560975609756 chr21 41741300 41741316 chr21_ridge_89105_5 5 16 0.3125 chr21 41740962 41741147 chr21_ridge_89104_9 9 185 0 . 04864864864864865 chr21 41732087 41732303 chr21_ridge_89076_ll 11 216 0.05092592592592592Chr21 41729603 41729834 chr21_ridge_89072_10 10 231 0.04329004329004329 chr21 41726473 41726745 chr21 ridge 89060 13 13 272 0.04779411764705882 chr21 41716057 41716111 chr21_ridge_89025_5 5 54 0.09259259259259259 chr21 41710944 41711284 chr21_ridge_89006_20 20 340 0.058823529411764705 chr21 41615781 41615840 chr21_ridge_88679_5 5 59 0.0847457627118644 chr21 41704196 41704342 chr21_ridge_88983_6 6 146 0.0410958904109589 chr21 41691353 41691473 chr21_ridge_88944_5 5 120 0.041666666666666664 chr21 41669571 41669736 chr21_ridge_88865_7 7 165 0.04242424242424243 chr21 41656601 41656746 chr21_ridge_88822_6 6 145 0.041379310344827586 chr21 41654234 41654504 chr21_ridge_88814_18 18 270 0.06666666666666667 chr21 41652180 41652275 chr21_ridge_88805_5 5 95 0.05263157894736842 chr21 41649750 41649841 chr21_ridge_88799_5 5 91 0.054945054945054944 chr21 41637010 41637117 chr21_ridge_88752_5 5 107 0.04672897196261682 chr21 41631629 41631953 chr21_ridge_88734_16 16 324 0.04938271604938271 chr21 41625584 41625726 chr21_ridge_88714_6 6 142 0.04225352112676056 chr21 41617719 41617825 chr21_ridge_88689_5 5 106 0.04716981132075472 chr21 41616852 41616925 chr21_ridge_88684_7 7 73 0.0958904109589041 chr21 41703260 41703480 chr21_ridge_88980_9 9 220 0.04090909090909091 chr21 41986927 41987050 chr21_ridge_89887_6 6 123 0.04878048780487805 chr21 41988234 41988343 chr21_ridge_89892_5 5 109 0.045871559633027525 chr21 41988481 41988937 chr21_ridge_89893_26 26 456 0.05701754385964912 chr21 42440517 42441214 chr21_ridge_91376_36 36 697 0.05164992826398852 chr21 42438008 42438216 chr21_ridge_91366_10 10 208 0.04807692307692308 chr21 42435524 42435659 chr21_ridge_91358_6 6 135 0 . 044444444444444446 chr21 42434201 42434267 chr21 ridge 91354 6 6 66 0.09090909090909091 chr21 42432542 42432693 chr21_ridge_91349_7 7 151 0.046357615894039736 chr21 42426924 42427002 chr21_ridge_91328_5 5 78 0.0641025641025641 chr21 42425238 42425435 chr21_ridge_91321_9 9 197 0.04568527918781726 chr21 42415834 42415996 chr21_ridge_91287_7 7 162 0.043209876543209874 chr21 42402750 42403336 chr21_ridge_91245_29 29 586 0.04948805460750853 chr21 42396881 42397029 chr21 ridge 91227 7 7 148 0.0472972972972973 chr21 42396677 42396774 chr21_ridge_91226_6 6 97 0.061855670103092786 chr21 42443382 42443590 chr21_ridge_91382_9 9 208 0.04326923076923077 chr21 42385461 42385556 chr21_ridge_91189_6 6 95 0.06315789473684211 chr21 42383600 42383705 chr21_ridge_91184_7 7 105 0.06666666666666667 chr21 42382931 42383281 chr21_ridge_91182_16 16 350 0.045714285714285714 chr21 42382143 42382230 chr21_ridge_91180_6 6 87 0.06896551724137931 chr21 42376131 42376352 chr21_ridge_91156_12 12 221 0.05429864253393665 chr21 42366202 42366306 chr21_ridge_91124_5 5 104 0.04807692307692308 chr21 42334870 42334897 chr21_ridge_91032_5 5 27 0.18518518518518517 chr21 42332328 42332616 chr21_ridge_91027_12 12 288 0.041666666666666664 chr21 42330451 42330532 chr21_ridge_91021_5 5 81 0.06172839506172839 chr21 42328817 42328928 chr21_ridge_91015_5 5 111 0.04504504504504504 chr21 42327449 42327586 chr21_ridge_91010_6 6 137 0.043795620437956206 chr21 42295332 42295544 chr21_ridge_90913_9 9 212 0.04245283018867924 chr21 42383893 42384406 chr21_ridge_91185_21 21 513 0.04093567251461988 chr21 42287172 42287324 chr21_ridge_90882_7 7 152 0.046052631578947366 chr21 42444642 42444746 chr21 ridge 91386 6 6 104 0.057692307692307696 chr21 42457952 42458016 chr21_ridge_91425_5 5 64 0.078125 chr21 42567611 42567733 chr21_ridge_91773_5 5 122 0.040983606557377046 chr21 42565043 42565160 chr21_ridge_91764_6 6 117 0.05128205128205128 chr21 42548590 42548691 chr21_ridge_91705_5 5 101 0.04950495049504951 chr21 42545387 42545443 chr21_ridge_91694_5 5 56 0.08928571428571429 chr21 42538801 42541266 chr21 ridge 91678 217 217 2465 0.08803245436105477 chr21 42535396 42535532 chr21_ridge_91666_6 6 136 0.04411764705882353 chr21 42535078 42535252 chr21_ridge_91665_7 7 174 0.040229885057471264 chr21 42531545 42531842 chr21_ridge_91656_13 13 297 0.04377104377104377 chr21 42522332 42522424 chr21_ridge_91626_6 6 92 0.06521739130434782 chr21 42520770 42520902 chr21_ridge_91621_7 7 132 0.05303030303030303 chr21 42520548 42520660 chr21_ridge_91620_5 5 112 0.044642857142857144 chr21 42447530 42448852 chr21_ridge_91395_53 53 1322 0.040090771558245086 chr21 42520179 42520445 chr21_ridge_91619_ll 11 266 0.041353383458646614 chr21 42512302 42512705 chr21_ridge_91597_17 17 403 0.04218362282878412Chr21 42498242 42498366 chr21_ridge_91547_5 5 124 0.04032258064516129 chr21 42496622 42496735 chr21 ridge 91543 6 6 113 0.05309734513274336 chr21 42494589 42494768 chr21_ridge_91535_8 8 179 0.0446927374301676 chr21 42488122 42488241 chr21_ridge_91516_5 5 119 0.04201680672268908 chr21 42481259 42481410 chr21_ridge_91496_7 7 151 0.046357615894039736 chr21 42480134 42480497 chr21_ridge_91492_16 16 363 0.0440771349862259 chr21 42471345 42471579 chr21_ridge_91469_10 10 234 0.042735042735042736 chr21 42468015 42468081 chr21_ridge_91459_5 5 66 0.07575757575757576 chr21 42465066 42465121 chr21_ridge_91446_6 6 55 0.10909090909090909 chr21 42460433 42460497 chr21_ridge_91431_6 6 64 0.09375 chr21 42514045 42514241 chr21_ridge_91602_8 8 196 0.04081632653061224 chr21 42582277 42582554 chr21_ridge_91820_12 12 277 0.04332129963898917 chr21 42284916 42285213 chr21_ridge_90874_15 15 297 0.050505050505050504 chr21 42262104 42262239 chr21_ridge_90793_7 7 135 0.05185185185185185 chr21 42123081 42123174 chr21_ridge_90335_5 5 93 0.053763440860215055 chr21 42102006 42102096 chr21_ridge_90269_5 5 90 0.05555555555555555 chr21 42100428 42100565 chr21_ridge_90263_6 6 137 0.043795620437956206 chr21 42093914 42094106 chr21_ridge_90243_8 8 192 0.041666666666666664 chr21 42090402 42090522 chr21_ridge_90231_5 5 120 0.041666666666666664 chr21 42084214 42084390 chr21_ridge_90210_16 16 176 0.09090909090909091 chr21 42080504 42080621 chr21_ridge_90197_9 9 117 0.07692307692307693 chr21 42077692 42078092 chr21_ridge_90190_16 16 400 0 . 04 chr21 42077464 42077585 chr21_ridge_90189_5 5 121 0.04132231404958678 chr21 42064654 42064917 chr21_ridge_90151_13 13 263 0.049429657794676805 chr21 42050739 42050814 chr21 ridge 90098 5 5 75 0.06666666666666667 chr21 42125990 42126086 chr21_ridge_90347_5 5 96 0.052083333333333336 chr21 42048778 42048872 chr21_ridge_90092_8 8 94 0.0851063829787234 chr21 42046579 42046844 chr21_ridge_90084_16 16 265 0.06037735849056604 chr21 42042330 42042552 chr21_ridge_90065_12 12 222 0.05405405405405406 chr21 42035321 42035387 chr21_ridge_90039_5 5 66 0.07575757575757576 chr21 42034686 42034818 chr21 ridge 90037 6 6 132 0.045454545454545456 chr21 42026927 42027045 chr21_ridge_90017_6 6 118 0.05084745762711865 chr21 42025462 42025612 chr21_ridge_90011_6 6 150 0.04 chr21 42020822 42020943 chr21_ridge_89995_5 5 121 0.04132231404958678 chr21 42013730 42013930 chr21_ridge_89969_ll 11 200 0.055 chr21 42010974 42011159 chr21_ridge_89961_10 10 185 0.05405405405405406 chr21 42010507 42010698 chr21_ridge_89960_9 9 191 0.04712041884816754 chr21 42006676 42006738 chr21_ridge_89951_5 5 62 0.08064516129032258 chr21 42046956 42047144 chr21_ridge_90085_9 9 188 0.047872340425531915 chr21 42276850 42276996 chr21_ridge_90841_6 6 146 0.0410958904109589 chr21 42128819 42128906 chr21_ridge_90358_5 5 87 0.05747126436781609 chr21 42144195 42144322 chr21_ridge_90410_6 6 127 0.047244094488188976 chr21 42259856 42259944 chr21_ridge_90785_6 6 88 0.06818181818181818 chr21 42256357 42256653 chr21_ridge_90770_14 14 296 0.0472972972972973 chr21 42255214 42255382 chr21_ridge_90766_8 8 168 0.047619047619047616 chr21 42251889 42252120 chr21_ridge_90757_14 14 231 0.06060606060606061 chr21 42233832 42233919 chr21_ridge_90704_5 5 87 0.05747126436781609 chr21 42227192 42227387 chr21 ridge 90683 9 9 195 0.046153846153846156 chr21 42220082 42220177 chr21_ridge_90661_6 6 95 0.06315789473684211 chr21 42218312 42219853 chr21_ridge_90660_112 112 1541 0.07268007787151201 chr21 42216884 42217001 chr21_ridge_90654_5 5 117 0.042735042735042736 chr21 42215471 42215642 chr21_ridge_90650_7 7 171 0.04093567251461988 chr21 42215195 42215297 chr21_ridge_90649_5 5 102 0.049019607843137254 chr21 42129017 42129253 chr21 ridge 90359 11 11 236 0.046610169491525424 chr21 42213509 42214390 chr21_ridge_90646_51 51 881 0.05788876276958002 chr21 42202267 42202382 chr21_ridge_90609_6 6 115 0.05217391304347826 chr21 42194791 42195084 chr21_ridge_90583_13 13 293 0.04436860068259386 chr21 42189709 42190568 chr21_ridge_90566_44 44 859 0.051222351571594875 chr21 42189121 42189240 chr21_ridge_90564_6 6 119 0.05042016806722689 chr21 42186489 42186611 chr21_ridge_90555_5 5 122 0.040983606557377046 chr21 42182143 42182230 chr21_ridge_90538_5 5 87 0.05747126436781609 chr21 42169542 42169652 chr21_ridge_90497_5 5 110 0.045454545454545456 chr21 42162964 42163634 chr21_ridge_90473_29 29 670 0.04328358208955224Chr21 42153798 42154083 chr21_ridge_90445_19 19 285 0.06666666666666667 chr21 42147771 42147854 chr21 ridge 90422 5 5 83 0.060240963855421686 chr21 42144636 42144822 chr21_ridge_90412_ll 11 186 0.05913978494623656 chr21 42206098 42206311 chr21_ridge_90620_12 12 213 0.056338028169014086 chr21 41491650 41491885 chr21_ridge_88251_10 10 235 0.0425531914893617 chr21 43215727 43215894 chr21_ridge_93546_9 9 167 0.05389221556886228 chr21 43218303 43218818 chr21_ridge_93556_26 26 515 0.05048543689320388 chr21 43919669 43920021 chr21_ridge_95422_17 17 352 0.048295454545454544 chr21 43915836 43917267 chr21_ridge_95413_98 98 1431 0.06848357791754019 chr21 43914838 43915101 chr21_ridge_95410_ll 11 263 0.04182509505703422 chr21 43913064 43913420 chr21_ridge_95405_15 15 356 0.042134831460674156 chr21 43912459 43912588 chr21_ridge_95403_7 7 129 0.05426356589147287 chr21 43909720 43909815 chr21_ridge_95392_5 5 95 0.05263157894736842 chr21 43902230 43902517 chr21_ridge_95369_12 12 287 0.041811846689895474 chr21 43900475 43900737 chr21_ridge_95363_12 12 262 0.04580152671755725 chr21 43900262 43900354 chr21_ridge_95362_6 6 92 0.06521739130434782 chr21 43895750 43896143 chr21_ridge_95350_17 17 393 0.043256997455470736 chr21 43895077 43895180 chr21_ridge_95348_6 6 103 0.05825242718446602 chr21 43894795 43894937 chr21_ridge_95347_10 10 142 0.07042253521126761 chr21 43894084 43894167 chr21_ridge_95344_6 6 83 0.07228915662650602 chr21 43892742 43892914 chr21_ridge_95339_7 7 172 0.040697674418604654 chr21 43892485 43892621 chr21_ridge_95338_6 6 136 0.04411764705882353 chr21 43892177 43892359 chr21_ridge_95337_9 9 182 0.04945054945054945 chr21 43891977 43892055 chr21_ridge_95336_6 6 78 0.07692307692307693 chr21 43891271 43891369 chr21 ridge 95333 6 6 98 0.061224489795918366 chr21 43890926 43891147 chr21_ridge_95332_9 9 221 0.04072398190045249 chr21 43886285 43886563 chr21_ridge_95316_22 22 278 0.07913669064748201 chr21 43882400 43882556 chr21_ridge_95306_7 7 156 0.04487179487179487 chr21 43880621 43880757 chr21_ridge_95299_6 6 136 0.04411764705882353 chr21 43876817 43876977 chr21_ridge_95288_7 7 160 0.04375 chr21 43921688 43921800 chr21 ridge 95429 6 6 112 0.05357142857142857 chr21 43932551 43935169 chr21_ridge_95467_191 191 2618 0.07295645530939648 chr21 43941065 43941416 chr21_ridge_95489_17 17 351 0.04843304843304843 chr21 43943002 43943149 chr21_ridge_95493_8 8 147 0.05442176870748299 chr21 43987935 43988221 chr21_ridge_95606_17 17 286 0.05944055944055944 chr21 43984690 43985463 chr21_ridge_95600_31 31 773 0.040103492884864166 chr21 43982681 43982995 chr21_ridge_95595_13 13 314 0.041401273885350316 chr21 43981472 43982328 chr21_ridge_95593_35 35 856 0.04088785046728972 chr21 43980027 43980243 chr21_ridge_95589_10 10 216 0.046296296296296294 chr21 43975864 43976745 chr21_ridge_95582_36 36 881 0.04086265607264472 chr21 43974471 43974568 chr21_ridge_95575_6 6 97 0.061855670103092786 chr21 43973154 43973291 chr21_ridge_95572_6 6 137 0.043795620437956206 chr21 43972883 43973009 chr21_ridge_95571_7 7 126 0.05555555555555555 chr21 43966544 43966875 chr21_ridge_95557_14 14 331 0.04229607250755287 chr21 43966275 43966379 chr21_ridge_95556_5 5 104 0.04807692307692308 chr21 43875038 43875214 chr21_ridge_95283_10 10 176 0.056818181818181816 chr21 43964294 43964335 chr21_ridge_95550_5 5 41 0.12195121951219512 chr21 43962756 43962815 chr21_ridge_95546_5 5 59 0.0847457627118644 chr21 43962406 43962567 chr21_ridge_95545_8 8 161 0.049689440993788817 chr21 43961541 43961710 chr21_ridge_95543_8 8 169 0.047337278106508875 chr21 43961225 43961402 chr21_ridge_95542_9 9 177 0.05084745762711865 chr21 43954798 43954975 chr21_ridge_95525_10 10 177 0.05649717514124294 chr21 43950931 43951528 chr21_ridge_95517_33 33 597 0.05527638190954774 chr21 43950422 43950533 chr21_ridge_95515_5 5 111 0.04504504504504504 chr21 43949746 43950003 chr21_ridge_95513_ll 11 257 0.042801556420233464 chr21 43949332 43949626 chr21_ridge_95512_12 12 294 0.04081632653061224 chr21 43948809 43948917 chr21_ridge_95511_6 6 108 0.05555555555555555 chr21 43944980 43945490 chr21_ridge_95498_22 22 510 0.043137254901960784 chr21 43963089 43963132 chr21_ridge_95548_5 5 43 0.11627906976744186 chr21 43874318 43874640 chr21_ridge_95281_15 15 322 0.046583850931677016 chr21 43872170 43872359 chr21_ridge_95277_8 8 189 0.042328042328042326 chr21 43870392 43870780 chr21_ridge_95272_19 19 388 0.04896907216494845 chr21 43797357 43797735 chr21_ridge_95056_16 16 378 0.042328042328042326chr21 43796339 43797045 chr21_ridge_95054_35 35 706 0.049575070821529746 chr21 43794390 43794562 chr21 ridge 95051 7 7 172 0 . 040697674418604654 chr21 43793272 43793551 chr21_ridge_95049_16 16 279 0.05734767025089606 chr21 43783245 43783512 chr21_ridge_95035_12 12 267 0.0449438202247191 chr21 43782306 43782555 chr21_ridge_95033_12 12 249 0.04819277108433735 chr21 43781950 43782176 chr21_ridge_95032_12 12 226 0.05309734513274336 chr21 43778557 43778724 chr21_ridge_95022_9 9 167 0.05389221556886228 chr21 43773125 43773296 chr21_ridge_95007_7 7 171 0.04093567251461988 chr21 43771002 43771355 chr21_ridge_95001_16 16 353 0.0453257790368272 chr21 43767305 43768376 chr21_ridge_94995_48 48 1071 0.04481792717086835 chr21 43803178 43803277 chr21_ridge_95071_5 5 99 0.050505050505050504 chr21 43767041 43767200 chr21_ridge_94994_13 13 159 0.08176100628930817 chr21 43762657 43762800 chr21_ridge_94981_7 7 143 0.04895104895104895 chr21 43762386 43762541 chr21_ridge_94980_8 8 155 0.05161290322580645 chr21 43762020 43762170 chr21_ridge_94979_7 7 150 0 . 04666666666666667 chr21 43761324 43761444 chr21_ridge_94976_8 8 120 0.06666666666666667 chr21 43744681 43744785 chr21_ridge_94920_5 5 104 0.04807692307692308 chr21 43741776 43741863 chr21_ridge_94914_7 7 87 0.08045977011494253 chr21 43741077 43741212 chr21_ridge_94912_6 6 135 0 . 044444444444444446 chr21 43730949 43731084 chr21_ridge_94888_6 6 135 0 . 044444444444444446 chr21 43730114 43730287 chr21_ridge_94885_13 13 173 0.07514450867052024 chr21 43729594 43730014 chr21_ridge_94884_20 20 420 0 . 047619047619047616 chr21 43725200 43726371 chr21_ridge_94875_62 62 1171 0.05294619982920581 chr21 43765725 43765818 chr21_ridge_94989_8 8 93 0.08602150537634409 chr21 43988362 43988935 chr21 ridge 95607 24 24 573 0 . 041884816753926704 chr21 43804798 43804944 chr21_ridge_95076_6 6 146 0.0410958904109589 chr21 43808544 43808649 chr21_ridge_95089_7 7 105 0.06666666666666667 chr21 43867969 43868083 chr21_ridge_95264_7 7 114 0.06140350877192982 chr21 43864642 43865124 chr21_ridge_95254_23 23 482 0.04771784232365145 chr21 43864048 43864537 chr21_ridge_95253_22 22 489 0 . 044989775051124746 chr21 43863332 43863506 chr21 ridge 95251 10 10 174 0.05747126436781609 chr21 43860194 43860410 chr21_ridge_95242_10 10 216 0 . 046296296296296294 chr21 43857600 43857705 chr21_ridge_95237_5 5 105 0 . 047619047619047616 chr21 43854915 43855035 chr21_ridge_95232_5 5 120 0 . 041666666666666664 chr21 43854145 43854278 chr21_ridge_95228_6 6 133 0 . 045112781954887216 chr21 43852215 43852336 chr21_ridge_95222_8 8 121 0.06611570247933884 chr21 43850687 43850772 chr21_ridge_95215_5 5 85 0.058823529411764705 chr21 43838476 43838745 chr21_ridge_95177_15 15 269 0 . 055762081784386616 chr21 43806480 43806769 chr21_ridge_95081_12 12 289 0.04152249134948097 chr21 43837760 43837877 chr21_ridge_95175_7 7 117 0.05982905982905983 chr21 43835522 43835776 chr21_ridge_95170_12 12 254 0 . 047244094488188976 chr21 43834972 43835417 chr21_ridge_95169_19 19 445 0.04269662921348315 chr21 43834210 43834316 chr21_ridge_95166_5 5 106 0.04716981132075472 chr21 43826379 43826595 chr21_ridge_95143_ll 11 216 0.05092592592592592 chr21 43824737 43825006 chr21_ridge_95140_ll 11 269 0 . 040892193308550186 chr21 43824024 43824333 chr21_ridge_95138_15 15 309 0.04854368932038835 chr21 43823724 43823863 chr21_ridge_95137_7 7 139 0.050359712230215826 chr21 43818156 43818293 chr21 ridge 95121 7 7 137 0.051094890510948905 chr21 43815474 43815736 chr21_ridge_95113_ll 11 262 0.04198473282442748 chr21 43812962 43813355 chr21_ridge_95107_16 16 393 0.04071246819338423 chr21 43812432 43812557 chr21_ridge_95105_5 5 125 0.04 chr21 43837327 43837556 chr21_ridge_95174_10 10 229 0 . 043668122270742356 chr21 43989047 43990776 chr21_ridge_95608_75 75 1729 0.04337767495662233 chr21 43991013 43991491 chr21 ridge 95610 20 20 478 0.04184100418410042 chr21 43991622 43991784 chr21_ridge_95611_8 8 162 0.04938271604938271 chr21 44135595 44135709 chr21_ridge_95971_7 7 114 0.06140350877192982 chr21 44132682 44132795 chr21_ridge_95964_5 5 113 0 . 04424778761061947 chr21 44130237 44130315 chr21_ridge_95955_6 6 78 0.07692307692307693 chr21 44128692 44128885 chr21_ridge_95951_8 8 193 0.04145077720207254 chr21 44126962 44127205 chr21_ridge_95943_13 13 243 0.053497942386831275 chr21 44125983 44126323 chr21_ridge_95941_15 15 340 0.04411764705882353 chr21 44122928 44123673 chr21_ridge_95938_32 32 745 0 . 042953020134228186 chr21 44118979 44119137 chr21_ridge_95929_8 8 158 0.05063291139240506Chr21 44115427 44115725 chr21_ridge_95918_13 13 298 0.0436241610738255 chr21 44113429 44113691 chr21 ridge 95911 19 19 262 0.07251908396946564 chr21 44112136 44113319 chr21_ridge_95910_56 56 1183 0.047337278106508875 chr21 44137688 44137791 chr21_ridge_95978_5 5 103 0.04854368932038835 chr21 44109954 44110816 chr21_ridge_95904_39 39 862 0.04524361948955916 chr21 44104813 44106793 chr21_ridge_95896_115 115 1980 0.05808080808080808 chr21 44104420 44104673 chr21_ridge_95895_ll 11 253 0.043478260869565216 chr21 44103383 44103491 chr21_ridge_95893_5 5 108 0.046296296296296294 chr21 44103136 44103267 chr21_ridge_95892_7 7 131 0.05343511450381679 chr21 44102861 44103005 chr21_ridge_95891_9 9 144 0.0625 chr21 44100668 44101136 chr21_ridge_95886_20 20 468 0.042735042735042736 chr21 44099199 44099519 chr21_ridge_95883_16 16 320 0.05 chr21 44098676 44099082 chr21_ridge_95882_17 17 406 0.04187192118226601 chr21 44098189 44098330 chr21_ridge_95880_8 8 141 0.05673758865248227 chr21 44097571 44097708 chr21_ridge_95878_7 7 137 0.051094890510948905 chr21 44096727 44096841 chr21_ridge_95875_6 6 114 0.05263157894736842 chr21 44107995 44108129 chr21_ridge_95900_14 14 134 0.1044776119402985 chr21 44095666 44096037 chr21_ridge_95872_15 15 371 0.04043126684636118 chr21 44138090 44138290 chr21_ridge_95979_8 8 200 0.04 chr21 44140224 44141110 chr21_ridge_95986_38 38 886 0.04288939051918736 chr21 44187813 44187872 chr21_ridge_96101_5 5 59 0.0847457627118644 chr21 44185375 44185481 chr21_ridge_96093_5 5 106 0.04716981132075472 chr21 44184480 44184737 chr21_ridge_96092_14 14 257 0.054474708171206226 chr21 44184242 44184309 chr21_ridge_96091_10 10 67 0.14925373134328357 chr21 44180355 44181017 chr21 ridge 96086 29 29 662 0.04380664652567976 chr21 44180159 44180254 chr21_ridge_96085_5 5 95 0.05263157894736842 chr21 44175210 44175333 chr21_ridge_96076_6 6 123 0.04878048780487805 chr21 44172003 44172147 chr21_ridge_96067_6 6 144 0.041666666666666664 chr21 44171738 44171843 chr21_ridge_96066_7 7 105 0.06666666666666667 chr21 44171279 44171620 chr21_ridge_96065_16 16 341 0.0469208211143695 chr21 44166798 44167283 chr21 ridge 96058 21 21 485 0.04329896907216495 chr21 44138754 44138871 chr21_ridge_95981_9 9 117 0.07692307692307693 chr21 44166517 44166604 chr21_ridge_96057_5 5 87 0.05747126436781609 chr21 44163402 44163525 chr21_ridge_96052_5 5 123 0.04065040650406504 chr21 44162401 44162534 chr21_ridge_96049_6 6 133 0.045112781954887216 chr21 44162138 44162227 chr21_ridge_96048_5 5 89 0.056179775280898875 chr21 44161743 44161884 chr21_ridge_96046_6 6 141 0.0425531914893617 chr21 44161479 44161636 chr21_ridge_96045_9 9 157 0.05732484076433121 chr21 44158533 44158709 chr21_ridge_96036_9 9 176 0.05113636363636364 chr21 44158296 44158422 chr21_ridge_96035_6 6 126 0.047619047619047616 chr21 44153525 44153624 chr21_ridge_96024_6 6 99 0.06060606060606061 chr21 44153100 44153215 chr21_ridge_96022_5 5 115 0.043478260869565216 chr21 44151705 44151773 chr21_ridge_96020_6 6 68 0.08823529411764706 chr21 44145100 44145275 chr21_ridge_96001_9 9 175 0.05142857142857143 chr21 44163639 44163743 chr21_ridge_96053_8 8 104 0.07692307692307693 chr21 43724739 43724978 chr21_ridge_94873_10 10 239 0.04184100418410042 chr21 44095452 44095547 chr21_ridge_95871_5 5 95 0.05263157894736842 chr21 44093767 44094326 chr21 ridge 95867 23 23 559 0.04114490161001789 chr21 44035181 44035360 chr21_ridge_95731_9 9 179 0.05027932960893855 chr21 44033342 44033531 chr21_ridge_95726_8 8 189 0.042328042328042326 chr21 44028426 44028566 chr21_ridge_95709_7 7 140 0.05 chr21 44026176 44026269 chr21_ridge_95703_5 5 93 0.053763440860215055 chr21 44025819 44025899 chr21_ridge_95702_5 5 80 0.0625 chr21 44021168 44021822 chr21 ridge 95686 27 27 654 0.04128440366972477 chr21 44020756 44020880 chr21_ridge_95685_6 6 124 0.04838709677419355 chr21 44017476 44017613 chr21_ridge_95676_7 7 137 0.051094890510948905 chr21 44015848 44016194 chr21_ridge_95670_14 14 346 0.04046242774566474 chr21 44015339 44015661 chr21_ridge_95669_14 14 322 0.043478260869565216 chr21 44014462 44014555 chr21_ridge_95667_5 5 93 0.053763440860215055 chr21 44036476 44037986 chr21_ridge_95733_77 77 1510 0.05099337748344371 chr21 44014060 44014224 chr21_ridge_95666_7 7 164 0.042682926829268296 chr21 44012363 44012534 chr21_ridge_95663_ll 11 171 0.06432748538011696 chr21 44011682 44012053 chr21_ridge_95661_17 17 371 0.04582210242587601Chr21 44007274 44010531 chr21_ridge_95658_285 285 3257 0.08750383788762665 chr21 44006454 44007054 chr21 ridge 95657 27 27 600 0.045 chr21 44004532 44004662 chr21_ridge_95652_10 10 130 0.07692307692307693 chr21 44003356 44003465 chr21_ridge_95648_6 6 109 0.05504587155963303 chr21 44003030 44003217 chr21_ridge_95647_16 16 187 0.0855614973262032 chr21 44002223 44002493 chr21_ridge_95644_ll 11 270 0.040740740740740744 chr21 44000708 44001316 chr21_ridge_95642_26 26 608 0.04276315789473684 chr21 43997939 43998105 chr21_ridge_95635_7 7 166 0.04216867469879518 chr21 43991899 43992088 chr21_ridge_95612_10 10 189 0.05291005291005291 chr21 44013139 44013958 chr21_ridge_95665_35 35 819 0.042735042735042736 chr21 44095113 44095299 chr21_ridge_95870_8 8 186 0.043010752688172046 chr21 44038127 44038249 chr21_ridge_95734_7 7 122 0.05737704918032787 chr21 44039404 44039573 chr21_ridge_95740_7 7 169 0.04142011834319527 chr21 44091184 44091473 chr21_ridge_95861_13 13 289 0.04498269896193772 chr21 44086219 44087234 chr21_ridge_95853_45 45 1015 0.04433497536945813 chr21 44085882 44086109 chr21_ridge_95852_ll 11 227 0.048458149779735685 chr21 44085688 44085780 chr21_ridge_95851_7 7 92 0.07608695652173914 chr21 44081536 44082087 chr21_ridge_95845_24 24 551 0.043557168784029036 chr21 44081014 44081430 chr21_ridge_95844_20 20 416 0.04807692307692308 chr21 44080273 44080493 chr21_ridge_95841_9 9 220 0.04090909090909091 chr21 44079704 44080173 chr21_ridge_95840_19 19 469 0.04051172707889126 chr21 44078526 44078833 chr21_ridge_95838_13 13 307 0.04234527687296417 chr21 44077706 44078426 chr21_ridge_95837_34 34 720 0.04722222222222222 chr21 44076364 44076741 chr21_ridge_95833_18 18 377 0.04774535809018567 chr21 44038494 44038613 chr21 ridge 95736 5 5 119 0.04201680672268908 chr21 44072469 44075121 chr21_ridge_95831_176 176 2652 0.06636500754147813 chr21 44071251 44071451 chr21_ridge_95827_10 10 200 0.05 chr21 44067070 44067264 chr21_ridge_95817_13 13 194 0.06701030927835051 chr21 44066558 44066828 chr21_ridge_95815_13 13 270 0.04814814814814815 chr21 44064689 44065064 chr21_ridge_95811_15 15 375 0.04 chr21 44064188 44064319 chr21 ridge 95809 6 6 131 0.04580152671755725 chr21 44063938 44064056 chr21_ridge_95808_8 8 118 0.06779661016949153 chr21 44058505 44058921 chr21_ridge_95796_20 20 416 0.04807692307692308 chr21 44057226 44058401 chr21_ridge_95795_47 47 1175 0.04 chr21 44050238 44050382 chr21_ridge_95772_7 7 144 0.04861111111111111 chr21 44047594 44047654 chr21_ridge_95767_5 5 60 0.08333333333333333 chr21 44046472 44046564 chr21_ridge_95763_7 7 92 0.07608695652173914 chr21 44072233 44072366 chr21_ridge_95830_6 6 133 0.045112781954887216 chr21 43216631 43216722 chr21_ridge_93550_5 5 91 0.054945054945054944 chr21 43722366 43722586 chr21_ridge_94866_10 10 220 0.045454545454545456 chr21 43718889 43719033 chr21_ridge_94858_7 7 144 0.04861111111111111 chr21 43362003 43362341 chr21_ridge_93909_17 17 338 0.05029585798816568 chr21 43355143 43355290 chr21_ridge_93887_7 7 147 0.047619047619047616 chr21 43354769 43355039 chr21_ridge_93886_ll 11 270 0.040740740740740744 chr21 43353412 43353596 chr21_ridge_93882_9 9 184 0.04891304347826087 chr21 43348236 43348546 chr21_ridge_93868_13 13 310 0.041935483870967745 chr21 43343001 43343397 chr21_ridge_93848_17 17 396 0.04292929292929293 chr21 43340698 43340805 chr21 ridge 93841 5 5 107 0.04672897196261682 chr21 43338852 43339004 chr21_ridge_93837_8 8 152 0.05263157894736842 chr21 43334507 43334767 chr21_ridge_93826_12 12 260 0.046153846153846156 chr21 43333459 43333654 chr21_ridge_93823_9 9 195 0.046153846153846156 chr21 43332354 43332971 chr21_ridge_93821_30 30 617 0.04862236628849271 chr21 43327599 43328259 chr21_ridge_93808_37 37 660 0.05606060606060606 chr21 43326904 43327290 chr21 ridge 93806 20 20 386 0.05181347150259067 chr21 43326589 43326725 chr21_ridge_93805_7 7 136 0.051470588235294115 chr21 43325808 43326072 chr21_ridge_93803_14 14 264 0.05303030303030303 chr21 43323776 43324070 chr21_ridge_93798_13 13 294 0.04421768707482993 chr21 43323193 43323246 chr21_ridge_93795_5 5 53 0.09433962264150944 chr21 43321232 43321505 chr21_ridge_93788_14 14 273 0.05128205128205128 chr21 43319109 43319450 chr21_ridge_93783_17 17 341 0.04985337243401759 chr21 43315266 43315341 chr21_ridge_93773_5 5 75 0.06666666666666667 chr21 43312827 43313143 chr21_ridge_93769_17 17 316 0.05379746835443038 chr21 43309100 43309417 chr21_ridge_93758_13 13 317 0.04100946372239748chr21 43308363 43308493 chr21_ridge_93756_7 7 130 0.05384615384615385 chr21 43365310 43365417 chr21 ridge 93914 6 6 107 0.056074766355140186 chr21 43368384 43368513 chr21_ridge_93923_6 6 129 0.046511627906976744 chr21 43371004 43371363 chr21_ridge_93931_16 16 359 0.04456824512534819 chr21 43372464 43375122 chr21_ridge_93935_198 198 2658 0.0744920993227991 chr21 43459123 43459240 chr21_ridge_94176_5 5 117 0.042735042735042736 chr21 43450258 43450371 chr21_ridge_94152_5 5 113 0.04424778761061947 chr21 43443820 43443943 chr21_ridge_94137_5 5 123 0.04065040650406504 chr21 43438472 43438792 chr21_ridge_94126_15 15 320 0.046875 chr21 43436675 43436914 chr21_ridge_94117_ll 11 239 0.04602510460251046 chr21 43429031 43431546 chr21_ridge_94099_286 286 2515 0.11371769383697813 chr21 43428308 43428606 chr21_ridge_94097_12 12 298 0.040268456375838924 chr21 43426292 43426532 chr21_ridge_94090_ll 11 240 0.04583333333333333 chr21 43414046 43414168 chr21_ridge_94048_5 5 122 0.040983606557377046 chr21 43412164 43412283 chr21_ridge_94042_6 6 119 0.05042016806722689 chr21 43402634 43402876 chr21_ridge_94010_12 12 242 0.049586776859504134 chr21 43304753 43305202 chr21_ridge_93748_21 21 449 0.0467706013363029 chr21 43391520 43392070 chr21_ridge_93986_22 22 550 0.04 chr21 43389657 43389929 chr21_ridge_93979_13 13 272 0.04779411764705882 chr21 43385777 43385993 chr21_ridge_93965_ll 11 216 0.05092592592592592 chr21 43384024 43384127 chr21_ridge_93961_5 5 103 0.04854368932038835 chr21 43383775 43383848 chr21_ridge_93960_5 5 73 0.0684931506849315 chr21 43382920 43383086 chr21_ridge_93958_7 7 166 0.04216867469879518 chr21 43379193 43379557 chr21_ridge_93949_16 16 364 0.04395604395604396 chr21 43378407 43378922 chr21 ridge 93947 24 24 515 0.04660194174757282 chr21 43377499 43377579 chr21_ridge_93943_5 5 80 0.0625 chr21 43376739 43376860 chr21_ridge_93940_6 6 121 0.049586776859504134 chr21 43376387 43376529 chr21_ridge_93939_9 9 142 0.06338028169014084 chr21 43375719 43376243 chr21_ridge_93938_26 26 524 0.04961832061068702 chr21 43390283 43390366 chr21_ridge_93981_5 5 83 0.060240963855421686 chr21 43304147 43304495 chr21 ridge 93747 14 14 348 0.040229885057471264 chr21 43303747 43303850 chr21_ridge_93746_5 5 103 0.04854368932038835 chr21 43303402 43303645 chr21_ridge_93745_ll 11 243 0.04526748971193416 chr21 43250933 43251177 chr21_ridge_93619_10 10 244 0.040983606557377046 chr21 43249104 43249190 chr21_ridge_93617_5 5 86 0.05813953488372093 chr21 43248238 43248997 chr21_ridge_93616_41 41 759 0.05401844532279315 chr21 43247892 43247994 chr21_ridge_93615_5 5 102 0.049019607843137254 chr21 43246201 43246697 chr21_ridge_93610_24 24 496 0.04838709677419355 chr21 43245232 43246085 chr21_ridge_93609_35 35 853 0.041031652989449004 chr21 43243126 43244020 chr21_ridge_93606_36 36 894 0.040268456375838924 chr21 43241397 43242634 chr21_ridge_93604_55 55 1237 0.0444624090541633 chr21 43240856 43241075 chr21_ridge_93602_13 13 219 0.0593607305936073 chr21 43239251 43240725 chr21_ridge_93601_63 63 1474 0.042740841248303935 chr21 43238973 43239078 chr21_ridge_93600_7 7 105 0.06666666666666667 chr21 43254333 43255760 chr21_ridge_93626_71 71 1427 0.049754730203223546 chr21 43238567 43238843 chr21_ridge_93599_13 13 276 0.04710144927536232 chr21 43234293 43236590 chr21_ridge_93592_104 104 2297 0.045276447540269917 chr21 43233019 43233440 chr21 ridge 93589 18 18 421 0.04275534441805225 chr21 43232063 43232462 chr21_ridge_93587_25 25 399 0.06265664160401002 chr21 43229617 43231350 chr21_ridge_93584_70 70 1733 0.040392383150605886 chr21 43229059 43229507 chr21_ridge_93583_27 27 448 0.060267857142857144 chr21 43228427 43228872 chr21_ridge_93582_20 20 445 0.0449438202247191 chr21 43227752 43227876 chr21_ridge_93579_6 6 124 0.04838709677419355 chr21 43222805 43223254 chr21 ridge 93570 22 22 449 0.04899777282850779 chr21 43221378 43222039 chr21_ridge_93567_35 35 661 0.0529500756429652 chr21 43220363 43220519 chr21_ridge_93565_8 8 156 0.05128205128205128 chr21 43220052 43220164 chr21_ridge_93564_7 7 112 0.0625 chr21 43237981 43238146 chr21_ridge_93596_7 7 165 0.04242424242424243 chr21 43463427 43463522 chr21_ridge_94193_5 5 95 0.05263157894736842 chr21 43256222 43256899 chr21_ridge_93628_36 36 677 0.053175775480059084 chr21 43259303 43259472 chr21_ridge_93638_8 8 169 0.047337278106508875 chr21 43302846 43303072 chr21_ridge_93744_10 10 226 0.04424778761061947 chr21 43302019 43302078 chr21_ridge_93741_6 6 59 0.1016949152542373Chr21 43298584 43300494 chr21_ridge_93736_204 204 1910 0.1068062827225131 chr21 43297884 43298178 chr21 ridge 93734 12 12 294 0.04081632653061224 chr21 43295680 43295954 chr21_ridge_93728_ll 11 274 0.040145985401459854 chr21 43291892 43292085 chr21_ridge_93718_9 9 193 0.046632124352331605 chr21 43290516 43290900 chr21_ridge_93715_18 18 384 0.046875 chr21 43289960 43290184 chr21_ridge_93714_9 9 224 0.04017857142857143 chr21 43289016 43289182 chr21_ridge_93712_9 9 166 0.05421686746987952 chr21 43287592 43287718 chr21_ridge_93708_8 8 126 0.06349206349206349 chr21 43287339 43287419 chr21_ridge_93707_5 5 80 0.0625 chr21 43258014 43258178 chr21_ridge_93632_7 7 164 0.042682926829268296 chr21 43285015 43285112 chr21_ridge_93700_5 5 97 0.05154639175257732 chr21 43282954 43283260 chr21_ridge_93692_18 18 306 0.058823529411764705 chr21 43280341 43280454 chr21_ridge_93687_5 5 113 0.04424778761061947 chr21 43277233 43277602 chr21_ridge_93682_15 15 369 0.04065040650406504 chr21 43274359 43275212 chr21_ridge_93678_41 41 853 0.04806565064478312 chr21 43273147 43273295 chr21_ridge_93675_8 8 148 0.05405405405405406 chr21 43272731 43272862 chr21_ridge_93673_8 8 131 0.061068702290076333 chr21 43270188 43270373 chr21_ridge_93667_8 8 185 0.043243243243243246 chr21 43267709 43267795 chr21_ridge_93661_7 7 86 0.08139534883720931 chr21 43265941 43266191 chr21_ridge_93657_10 10 250 0.04 chr21 43262622 43262962 chr21_ridge_93649_14 14 340 0.041176470588235294 chr21 43259590 43260010 chr21_ridge_93639_21 21 420 0.05 chr21 43283989 43284298 chr21_ridge_93696_16 16 309 0.05177993527508091 chr21 43464796 43464924 chr21_ridge_94196_6 6 128 0.046875 chr21 43468082 43468268 chr21 ridge 94208 8 8 186 0.043010752688172046 chr21 43468424 43468885 chr21_ridge_94209_22 22 461 0.04772234273318872 chr21 43653439 43653564 chr21_ridge_94705_6 6 125 0.048 chr21 43650413 43650559 chr21_ridge_94695_6 6 146 0.0410958904109589 chr21 43648274 43648365 chr21_ridge_94689_6 6 91 0.06593406593406594 chr21 43647489 43647568 chr21_ridge_94686_6 6 79 0.0759493670886076 chr21 43642333 43642468 chr21 ridge 94669 7 7 135 0.05185185185185185 chr21 43640268 43640819 chr21_ridge_94662_28 28 551 0.050816696914700546 chr21 43638594 43640131 chr21_ridge_94661_136 136 1537 0.08848405985686401 chr21 43637471 43637596 chr21_ridge_94657_5 5 125 0.04 chr21 43632811 43633092 chr21_ridge_94642_13 13 281 0.046263345195729534 chr21 43631267 43631319 chr21_ridge_94638_5 5 52 0.09615384615384616 chr21 43617897 43617979 chr21_ridge_94595_5 5 82 0.06097560975609756 chr21 43653856 43653965 chr21_ridge_94707_5 5 109 0.045871559633027525 chr21 43615061 43615301 chr21_ridge_94586_10 10 240 0.041666666666666664 chr21 43609250 43609396 chr21_ridge_94572_8 8 146 0.0547945205479452 chr21 43605116 43605474 chr21_ridge_94559_15 15 358 0.04189944134078212 chr21 43600029 43600148 chr21_ridge_94544_5 5 119 0.04201680672268908 chr21 43592696 43593605 chr21_ridge_94524_43 43 909 0.047304730473047306 chr21 43592305 43592576 chr21_ridge_94523_12 12 271 0.04428044280442804 chr21 43585782 43586641 chr21_ridge_94508_38 38 859 0.04423748544819558 chr21 43582961 43583062 chr21_ridge_94500_5 5 101 0.04950495049504951 chr21 43578442 43578754 chr21_ridge_94491_14 14 312 0.04487179487179487 chr21 43578135 43578317 chr21 ridge 94490 8 8 182 0.04395604395604396 chr21 43575603 43575870 chr21_ridge_94485_12 12 267 0.0449438202247191 chr21 43575207 43575466 chr21_ridge_94484_ll 11 259 0.04247104247104247 chr21 43611733 43611828 chr21_ridge_94577_5 5 95 0.05263157894736842 chr21 43574950 43575056 chr21_ridge_94483_5 5 106 0.04716981132075472 chr21 43654525 43655975 chr21_ridge_94709_103 103 1450 0.07103448275862069 chr21 43660589 43660886 chr21 ridge 94726 13 13 297 0.04377104377104377 chr21 43718628 43718744 chr21_ridge_94857_5 5 116 0.04310344827586207 chr21 43715774 43716647 chr21_ridge_94851_40 40 873 0.045819014891179836 chr21 43715587 43715655 chr21_ridge_94850_6 6 68 0.08823529411764706 chr21 43714983 43715435 chr21_ridge_94849_21 21 452 0.046460176991150445 chr21 43713938 43714837 chr21_ridge_94848_37 37 899 0.041156840934371525 chr21 43711029 43712345 chr21_ridge_94840_56 56 1316 0.0425531914893617 chr21 43709953 43710399 chr21_ridge_94837_21 21 446 0.04708520179372197 chr21 43704193 43704897 chr21_ridge_94827_30 30 704 0.04261363636363636 chr21 43703926 43704048 chr21_ridge_94826_5 5 122 0.040983606557377046Chr21 43702185 43702652 chr21_ridge_94823_23 23 467 0.04925053533190578 chr21 43696229 43696511 chr21 ridge 94814 13 13 282 0.04609929078014184 chr21 43656280 43656653 chr21_ridge_94711_15 15 373 0 . 040214477211796246 chr21 43689355 43689393 chr21_ridge_94802_5 5 38 0.13157894736842105 chr21 43674906 43675027 chr21_ridge_94769_5 5 121 0.04132231404958678 chr21 43674716 43674757 chr21_ridge_94768_5 5 41 0.12195121951219512 chr21 43673115 43673197 chr21_ridge_94762_5 5 82 0.06097560975609756 chr21 43672156 43672331 chr21_ridge_94760_7 7 175 0.04 chr21 43670171 43670324 chr21_ridge_94756_8 8 153 0.05228758169934641 chr21 43669241 43669382 chr21_ridge_94752_6 6 141 0.0425531914893617 chr21 43664407 43664510 chr21_ridge_94737_5 5 103 0.04854368932038835 chr21 43663949 43664224 chr21_ridge_94736_19 19 275 0.06909090909090909 chr21 43663543 43663625 chr21_ridge_94734_7 7 82 0.08536585365853659 chr21 43663324 43663435 chr21_ridge_94733_7 7 111 0.06306306306306306 chr21 43660986 43661069 chr21_ridge_94727_7 7 83 0.08433734939759036 chr21 43687219 43687354 chr21_ridge_94796_8 8 135 0.05925925925925926 chr21 43721487 43721824 chr21_ridge_94863_17 17 337 0 . 050445103857566766 chr21 43573778 43574029 chr21_ridge_94479_ll 11 251 0 . 043824701195219126 chr21 43570916 43571092 chr21_ridge_94471_8 8 176 0 . 045454545454545456 chr21 43518975 43519875 chr21_ridge_94343_39 39 900 0.043333333333333335 chr21 43518604 43518831 chr21_ridge_94342_ll 11 227 0 . 048458149779735685 chr21 43518232 43518341 chr21_ridge_94341_6 6 109 0.05504587155963303 chr21 43509202 43509292 chr21_ridge_94316_6 6 90 0.06666666666666667 chr21 43506190 43506385 chr21_ridge_94307_9 9 195 0.046153846153846156 chr21 43501238 43501386 chr21 ridge 94298 6 6 148 0.04054054054054054 chr21 43498097 43498165 chr21_ridge_94292_5 5 68 0.07352941176470588 chr21 43497623 43497736 chr21_ridge_94290_6 6 113 0.05309734513274336 chr21 43497361 43497510 chr21_ridge_94289_10 10 149 0.06711409395973154 chr21 43495996 43496602 chr21_ridge_94285_33 33 606 0 . 054455445544554455 chr21 43495699 43495893 chr21_ridge_94284_10 10 194 0.05154639175257732 chr21 43520063 43520183 chr21_ridge_94344_5 5 120 0 . 041666666666666664 chr21 43492298 43492389 chr21_ridge_94276_5 5 91 0 . 054945054945054944 chr21 43487587 43488392 chr21_ridge_94258_35 35 805 0 . 043478260869565216 chr21 43486412 43486516 chr21_ridge_94253_7 7 104 0.0673076923076923 chr21 43486021 43486206 chr21_ridge_94252_9 9 185 0 . 04864864864864865 chr21 43479878 43480110 chr21_ridge_94243_10 10 232 0.04310344827586207 chr21 43479288 43479393 chr21_ridge_94240_5 5 105 0 . 047619047619047616 chr21 43478096 43478253 chr21_ridge_94236_10 10 157 0.06369426751592357 chr21 43477345 43477452 chr21_ridge_94234_8 8 107 0.07476635514018691 chr21 43475877 43476035 chr21_ridge_94231_7 7 158 0.04430379746835443 chr21 43475670 43475755 chr21_ridge_94230_5 5 85 0 . 058823529411764705 chr21 43475407 43475536 chr21_ridge_94229_6 6 129 0 . 046511627906976744 chr21 43472037 43472233 chr21_ridge_94218_8 8 196 0.04081632653061224 chr21 43490243 43490339 chr21_ridge_94269_6 6 96 0.0625 chr21 43573099 43573413 chr21_ridge_94477_13 13 314 0 . 041401273885350316 chr21 43520473 43520628 chr21_ridge_94346_9 9 155 0.05806451612903226 chr21 43521290 43521418 chr21_ridge_94349_9 9 128 0.0703125 chr21 43570255 43570496 chr21 ridge 94468 10 10 241 0.04149377593360996 chr21 43568948 43569496 chr21_ridge_94465_22 22 548 0 . 040145985401459854 chr21 43566792 43567348 chr21_ridge_94460_26 26 556 0 . 046762589928057555 chr21 43563323 43563477 chr21_ridge_94450_7 7 154 0 . 045454545454545456 chr21 43562774 43562952 chr21_ridge_94449_8 8 178 0.0449438202247191 chr21 43555224 43555302 chr21_ridge_94437_6 6 78 0.07692307692307693 chr21 43553360 43553504 chr21 ridge 94432 8 8 144 0.05555555555555555 chr21 43551472 43551526 chr21_ridge_94426_5 5 54 0.09259259259259259 chr21 43550329 43550365 chr21_ridge_94423_5 5 36 0.1388888888888889 chr21 43547605 43548217 chr21_ridge_94418_32 32 612 0.05228758169934641 chr21 43546977 43547318 chr21_ridge_94417_17 17 341 0.04985337243401759 chr21 43520936 43521079 chr21_ridge_94348_6 6 143 0.04195804195804196 chr21 43545480 43545563 chr21_ridge_94413_7 7 83 0.08433734939759036 chr21 43541639 43541869 chr21_ridge_94406_12 12 230 0.05217391304347826 chr21 43541199 43541519 chr21_ridge_94405_14 14 320 0.04375 chr21 43539685 43539815 chr21_ridge_94400_6 6 130 0 . 046153846153846156Chr21 43538955 43539523 chr21_ridge_94399_23 23 568 0.040492957746478875 chr21 43537367 43537465 chr21 ridge 94392 5 5 98 0.05102040816326531 chr21 43533510 43533619 chr21_ridge_94378_5 5 109 0.045871559633027525 chr21 43531673 43531964 chr21_ridge_94371_13 13 291 0.044673539518900345 chr21 43529507 43529853 chr21_ridge_94367_19 19 346 0.05491329479768786 chr21 43525867 43526871 chr21_ridge_94362_46 46 1004 0.045816733067729085 chr21 43523777 43524214 chr21_ridge_94358_22 22 437 0.05034324942791762 chr21 43522956 43523056 chr21_ridge_94353_6 6 100 0 . 06 chr21 43542563 43542819 chr21_ridge_94409_16 16 256 0.0625 chr21 44188197 44188357 chr21_ridge_96102_7 7 160 0.04375 chr21 41491268 41491439 chr21_ridge_88250_7 7 171 0.04093567251461988 chr21 41489610 41489746 chr21_ridge_88243_7 7 136 0.051470588235294115 chr21 38655388 38656038 chr21_ridge_79084_48 48 650 0.07384615384615385 chr21 38653440 38653639 chr21_ridge_79080_9 9 199 0.04522613065326633 chr21 38650391 38650679 chr21_ridge_79071_12 12 288 0.041666666666666664 chr21 38650024 38650115 chr21_ridge_79069_6 6 91 0.06593406593406594 chr21 38649563 38649821 chr21_ridge_79068_13 13 258 0.050387596899224806 chr21 38648149 38648186 chr21_ridge_79060_5 5 37 0.13513513513513514 chr21 38647349 38647625 chr21_ridge_79058_14 14 276 0.050724637681159424 chr21 38641880 38642119 chr21_ridge_79042_12 12 239 0.0502092050209205 chr21 38638996 38640509 chr21_ridge_79037_132 132 1513 0.08724388631857237 chr21 38638239 38638512 chr21_ridge_79035_17 17 273 0.06227106227106227 chr21 38632145 38632250 chr21_ridge_79011_5 5 105 0.047619047619047616 chr21 38630008 38631315 chr21_ridge_79007_78 78 1307 0.05967865340474369 chr21 38629492 38629903 chr21 ridge 79006 20 20 411 0.04866180048661801 chr21 38627679 38627788 chr21_ridge_78997_5 5 109 0.045871559633027525 chr21 38619571 38619641 chr21_ridge_78964_6 6 70 0.08571428571428572 chr21 38613124 38613187 chr21_ridge_78949_5 5 63 0.07936507936507936 chr21 38611200 38611378 chr21_ridge_78942_10 10 178 0.056179775280898875 chr21 38610439 38610869 chr21_ridge_78940_18 18 430 0.04186046511627907 chr21 38608509 38608601 chr21 ridge 78933 6 6 92 0.06521739130434782 chr21 38607586 38607723 chr21_ridge_78929_6 6 137 0.043795620437956206 chr21 38604568 38604880 chr21_ridge_78921_17 17 312 0.05448717948717949 chr21 38604023 38604377 chr21_ridge_78920_18 18 354 0.05084745762711865 chr21 38603471 38603813 chr21_ridge_78919_17 17 342 0.049707602339181284 chr21 38656384 38656499 chr21_ridge_79086_8 8 115 0.06956521739130435 chr21 38657640 38657742 chr21_ridge_79091_7 7 102 0.06862745098039216 chr21 38659645 38659819 chr21_ridge_79094_7 7 174 0.040229885057471264 chr21 38660121 38660418 chr21_ridge_79096_12 12 297 0.04040404040404041 chr21 38748535 38748607 chr21_ridge_79354_5 5 72 0.06944444444444445 chr21 38748248 38748349 chr21_ridge_79353_5 5 101 0.04950495049504951 chr21 38746883 38747097 chr21_ridge_79350_ll 11 214 0.0514018691588785 chr21 38737849 38740959 chr21_ridge_79333_335 335 3110 0.10771704180064309 chr21 38733812 38734019 chr21_ridge_79323_9 9 207 0.043478260869565216 chr21 38726976 38727136 chr21_ridge_79303_8 8 160 0.05 chr21 38725676 38725750 chr21_ridge_79299_5 5 74 0.06756756756756757 chr21 38724929 38725135 chr21_ridge_79296_9 9 206 0.043689320388349516 chr21 38715506 38715727 chr21 ridge 79271 9 9 221 0.04072398190045249 chr21 38711682 38711704 chr21_ridge_79258_5 5 22 0.22727272727272727 chr21 38711220 38711309 chr21_ridge_79256_5 5 89 0.056179775280898875 chr21 38602913 38603354 chr21_ridge_78918_22 22 441 0.049886621315192746 chr21 38710843 38710892 chr21_ridge_79254_6 6 49 0.12244897959183673 chr21 38702506 38702712 chr21_ridge_79221_9 9 206 0.043689320388349516 chr21 38696583 38696763 chr21 ridge 79209 8 8 180 0 . 044444444444444446 chr21 38694249 38694294 chr21_ridge_79199_5 5 45 0.1111111111111111 chr21 38690439 38690876 chr21_ridge_79189_22 22 437 0.05034324942791762 chr21 38685464 38685719 chr21_ridge_79175_13 13 255 0.050980392156862744 chr21 38683756 38684034 chr21_ridge_79171_17 17 278 0.06115107913669065 chr21 38682788 38683059 chr21_ridge_79168_12 12 271 0.04428044280442804 chr21 38670166 38670231 chr21_ridge_79132_5 5 65 0.07692307692307693 chr21 38669789 38669891 chr21_ridge_79130_5 5 102 0.049019607843137254 chr21 38666428 38666537 chr21_ridge_79119_5 5 109 0.045871559633027525 chr21 38663364 38663642 chr21_ridge_79109_15 15 278 0.0539568345323741Chr21 38709201 38709336 chr21_ridge_79247_6 6 135 0 . 044444444444444446 chr21 38600046 38600863 chr21 ridge 78909 47 47 817 0.05752753977968176 chr21 38599414 38599657 chr21_ridge_78907_12 12 243 0.04938271604938271 chr21 38597757 38598066 chr21_ridge_78902_15 15 309 0.04854368932038835 chr21 38449063 38449286 chr21_ridge_78447_ll 11 223 0.04932735426008968 chr21 38444161 38447230 chr21_ridge_78442_224 224 3069 0.07298794395568589 chr21 38443092 38443355 chr21_ridge_78437_14 14 263 0.053231939163498096 chr21 38438249 38438369 chr21_ridge_78419_8 8 120 0.06666666666666667 chr21 38436426 38436622 chr21_ridge_78414_8 8 196 0.04081632653061224 chr21 38425248 38425474 chr21_ridge_78377_ll 11 226 0.048672566371681415 chr21 38423241 38423406 chr21_ridge_78368_7 7 165 0.04242424242424243 chr21 38417501 38417649 chr21_ridge_78350_6 6 148 0.04054054054054054 chr21 38411728 38411798 chr21_ridge_78329_5 5 70 0.07142857142857142 chr21 38410708 38410839 chr21_ridge_78327_6 6 131 0.04580152671755725 chr21 38401964 38402018 chr21_ridge_78300_5 5 54 0.09259259259259259 chr21 38454201 38454464 chr21_ridge_78460_18 18 263 0.06844106463878327 chr21 38401240 38401331 chr21_ridge_78298_5 5 91 0.054945054945054944 chr21 38389175 38389284 chr21_ridge_78260_6 6 109 0.05504587155963303 chr21 38384501 38384694 chr21_ridge_78242_8 8 193 0.04145077720207254 chr21 38383986 38384383 chr21_ridge_78241_23 23 397 0.05793450881612091 chr21 38383705 38383854 chr21_ridge_78240_6 6 149 0.040268456375838924 chr21 38383307 38383599 chr21_ridge_78239_17 17 292 0.05821917808219178 chr21 38381977 38383206 chr21_ridge_78238_52 52 1229 0.04231082180634662 chr21 38381601 38381702 chr21_ridge_78236_5 5 101 0.04950495049504951 chr21 38377217 38381325 chr21 ridge 78235 263 263 4108 0.06402142161635832 chr21 38374821 38374887 chr21_ridge_78229_5 5 66 0.07575757575757576 chr21 38367697 38367958 chr21_ridge_78206_12 12 261 0.04597701149425287 chr21 38366499 38367575 chr21_ridge_78205_61 61 1076 0.056691449814126396 chr21 38397146 38397460 chr21_ridge_78283_17 17 314 0.054140127388535034 chr21 38748740 38748791 chr21_ridge_79355_5 5 51 0.09803921568627451 chr21 38463965 38464180 chr21 ridge 78490 11 11 215 0.05116279069767442 chr21 38470305 38470424 chr21_ridge_78507_5 5 119 0.04201680672268908 chr21 38592539 38594005 chr21_ridge_78887_93 93 1466 0.06343792633015007 chr21 38589210 38589710 chr21_ridge_78872_26 26 500 0.052 chr21 38587834 38587968 chr21_ridge_78868_6 6 134 0.04477611940298507 chr21 38580974 38581267 chr21_ridge_78854_13 13 293 0.04436860068259386 chr21 38580419 38580649 chr21_ridge_78852_10 10 230 0.043478260869565216 chr21 38575901 38576238 chr21_ridge_78838_18 18 337 0.05341246290801187 chr21 38575510 38575618 chr21_ridge_78836_6 6 108 0.05555555555555555 chr21 38575171 38575310 chr21_ridge_78835_6 6 139 0.04316546762589928 chr21 38570158 38570262 chr21_ridge_78819_5 5 104 0.04807692307692308 chr21 38569500 38569645 chr21_ridge_78817_6 6 145 0.041379310344827586 chr21 38569233 38569352 chr21_ridge_78816_5 5 119 0.04201680672268908 chr21 38465369 38465619 chr21_ridge_78493_14 14 250 0.056 chr21 38566514 38566756 chr21_ridge_78809_10 10 242 0.04132231404958678 chr21 38547488 38547617 chr21_ridge_78752_9 9 129 0.06976744186046512 chr21 38547281 38547384 chr21_ridge_78751_5 5 103 0.04854368932038835 chr21 38536355 38536462 chr21 ridge 78718 5 5 107 0.04672897196261682 chr21 38526880 38527295 chr21_ridge_78686_21 21 415 0.05060240963855422 chr21 38511459 38511552 chr21_ridge_78639_5 5 93 0.053763440860215055 chr21 38507747 38507871 chr21_ridge_78628_5 5 124 0.04032258064516129 chr21 38483098 38483193 chr21_ridge_78549_5 5 95 0.05263157894736842 chr21 38482685 38482759 chr21_ridge_78547_5 5 74 0.06756756756756757 chr21 38482468 38482578 chr21_ridge_78546_5 5 110 0.045454545454545456 chr21 38476579 38476883 chr21_ridge_78528_15 15 304 0.049342105263157895 chr21 38472931 38473099 chr21_ridge_78517_7 7 168 0.041666666666666664 chr21 38557420 38557582 chr21_ridge_78779_7 7 162 0.043209876543209874 chr21 38758571 38758746 chr21_ridge_79386_8 8 175 0.045714285714285714 chr21 38765149 38765252 chr21_ridge_79404_5 5 103 0.04854368932038835 chr21 38771137 38771247 chr21_ridge_79426_8 8 110 0.07272727272727272 chr21 39188168 39188229 chr21_ridge_80787_7 7 61 0.11475409836065574 chr21 39169110 39169347 chr21_ridge_80717_19 19 237 0.08016877637130802 chr21 39166995 39167044 chr21_ridge_80712_5 5 49 0.10204081632653061Chr21 39135176 39135359 chr21_ridge_80604_8 8 183 0.04371584699453552 chr21 39121517 39121702 chr21 ridge 80564 10 10 185 0.05405405405405406 chr21 39121112 39121187 chr21_ridge_80562_5 5 75 0.06666666666666667 chr21 39109733 39109901 chr21_ridge_80520_7 7 168 0.041666666666666664 chr21 39107605 39107719 chr21_ridge_80513_5 5 114 0.043859649122807015 chr21 39107193 39107415 chr21_ridge_80512_10 10 222 0.04504504504504504 chr21 39093024 39093309 chr21_ridge_80459_25 25 285 0.08771929824561403 chr21 39087223 39087499 chr21_ridge_80434_13 13 276 0.04710144927536232 chr21 39188924 39189014 chr21_ridge_80790_6 6 90 0.06666666666666667 chr21 39086985 39087117 chr21_ridge_80433_6 6 132 0.045454545454545456 chr21 39085785 39085907 chr21_ridge_80431_5 5 122 0.040983606557377046 chr21 39065708 39065950 chr21_ridge_80371_10 10 242 0.04132231404958678 chr21 39059461 39059568 chr21_ridge_80351_6 6 107 0.056074766355140186 chr21 39058737 39058856 chr21_ridge_80348_5 5 119 0.04201680672268908 chr21 39057704 39057962 chr21_ridge_80344_13 13 258 0.050387596899224806 chr21 39048127 39048212 chr21_ridge_80312_5 5 85 0.058823529411764705 chr21 39047349 39047989 chr21_ridge_80311_43 43 640 0.0671875 chr21 39047004 39047185 chr21_ridge_80310_8 8 181 0.04419889502762431 chr21 39044685 39044775 chr21_ridge_80302_5 5 90 0.05555555555555555 chr21 39043445 39043524 chr21_ridge_80296_5 5 79 0.06329113924050633 chr21 39040911 39041005 chr21_ridge_80290_5 5 94 0.05319148936170213 chr21 39086630 39086819 chr21_ridge_80432_9 9 189 0.047619047619047616 chr21 39039775 39039993 chr21_ridge_80286_20 20 218 0.09174311926605505 chr21 39190493 39190517 chr21_ridge_80795_5 5 24 0.20833333333333334 chr21 39201439 39201597 chr21 ridge 80829 8 8 158 0.05063291139240506 chr21 39338657 39338841 chr21_ridge_81279_14 14 184 0.07608695652173914 chr21 39335766 39335868 chr21_ridge_81271_5 5 102 0.049019607843137254 chr21 39334790 39335054 chr21_ridge_81268_12 12 264 0.045454545454545456 chr21 39331593 39331834 chr21_ridge_81260_10 10 241 0.04149377593360996 chr21 39329275 39329472 chr21_ridge_81251_8 8 197 0.04060913705583756 chr21 39327269 39327386 chr21 ridge 81242 5 5 117 0.042735042735042736 chr21 39324959 39325054 chr21_ridge_81234_5 5 95 0.05263157894736842 chr21 39324566 39324846 chr21_ridge_81233_12 12 280 0.04285714285714286 chr21 39315680 39315942 chr21_ridge_81208_16 16 262 0.061068702290076333 chr21 39311489 39311664 chr21_ridge_81197_7 7 175 0.04 chr21 39299316 39299373 chr21_ridge_81161_5 5 57 0.08771929824561403 chr21 39199190 39199299 chr21_ridge_80825_6 6 109 0.05504587155963303 chr21 39291594 39291674 chr21_ridge_81137_5 5 80 0.0625 chr21 39286471 39287138 chr21_ridge_81126_32 32 667 0.047976011994003 chr21 39285630 39286367 chr21_ridge_81125_30 30 737 0.0407055630936228 chr21 39260954 39261067 chr21_ridge_81048_5 5 113 0.04424778761061947 chr21 39255864 39255968 chr21_ridge_81030_5 5 104 0.04807692307692308 chr21 39252357 39252593 chr21_ridge_81016_10 10 236 0.0423728813559322 chr21 39240807 39240955 chr21_ridge_80975_6 6 148 0.04054054054054054 chr21 39236256 39236384 chr21_ridge_80955_7 7 128 0.0546875 chr21 39230419 39230689 chr21_ridge_80935_15 15 270 0.05555555555555555 chr21 39217678 39217697 chr21_ridge_80884_5 5 19 0.2631578947368421 chr21 39212792 39212902 chr21 ridge 80871 5 5 110 0.045454545454545456 chr21 39204627 39204792 chr21_ridge_80840_7 7 165 0.04242424242424243 chr21 39287642 39289374 chr21_ridge_81128_118 118 1732 0.06812933025404157 chr21 38365255 38365460 chr21_ridge_78202_10 10 205 0.04878048780487805 chr21 39033962 39034380 chr21_ridge_80269_17 17 418 0.04066985645933014 chr21 39022753 39022851 chr21_ridge_80228_5 5 98 0.05102040816326531 chr21 38923987 38924226 chr21 ridge 79914 13 13 239 0.05439330543933055 chr21 38907336 38907456 chr21_ridge_79865_5 5 120 0.041666666666666664 chr21 38903463 38903534 chr21_ridge_79851_5 5 71 0.07042253521126761 chr21 38903198 38903333 chr21_ridge_79850_7 7 135 0.05185185185185185 chr21 38902905 38903083 chr21_ridge_79849_9 9 178 0.05056179775280899 chr21 38901988 38902156 chr21_ridge_79845_7 7 168 0.041666666666666664 chr21 38900547 38900767 chr21_ridge_79839_9 9 220 0.04090909090909091 chr21 38899550 38899664 chr21_ridge_79834_5 5 114 0.043859649122807015 chr21 38891634 38892205 chr21_ridge_79805_24 24 571 0.04203152364273205 chr21 38889559 38889731 chr21_ridge_79799_7 7 172 0.040697674418604654Chr21 38888307 38888410 chr21_ridge_79794_5 5 103 0.04854368932038835 chr21 38925305 38925555 chr21 ridge 79917 10 10 250 0.04 chr21 38887766 38887870 chr21_ridge_79791_5 5 104 0.04807692307692308 chr21 38867880 38867947 chr21_ridge_79726_5 5 67 0.07462686567164178 chr21 38862839 38862912 chr21_ridge_79711_5 5 73 0.0684931506849315 chr21 38856312 38856433 chr21_ridge_79689_6 6 121 0.049586776859504134 chr21 38852959 38853089 chr21_ridge_79679_7 7 130 0.05384615384615385 chr21 38851988 38852328 chr21_ridge_79677_15 15 340 0.04411764705882353 chr21 38849243 38849340 chr21_ridge_79668_5 5 97 0.05154639175257732 chr21 38848349 38848546 chr21_ridge_79665_8 8 197 0.04060913705583756 chr21 38835391 38835509 chr21_ridge_79626_6 6 118 0.05084745762711865 chr21 38823585 38824041 chr21_ridge_79588_21 21 456 0.046052631578947366 chr21 38811803 38811910 chr21_ridge_79548_5 5 107 0.04672897196261682 chr21 38773349 38773432 chr21_ridge_79432_5 5 83 0.060240963855421686 chr21 38878409 38878639 chr21_ridge_79760_12 12 230 0.05217391304347826 chr21 39023773 39023878 chr21_ridge_80233_5 5 105 0.047619047619047616 chr21 38925700 38925846 chr21_ridge_79918_8 8 146 0.0547945205479452 chr21 38929813 38929937 chr21_ridge_79932_5 5 124 0.04032258064516129 chr21 39021761 39021892 chr21_ridge_80225_7 7 131 0.05343511450381679 chr21 39021136 39021360 chr21_ridge_80223_ll 11 224 0.049107142857142856 chr21 39018877 39019352 chr21_ridge_80219_22 22 475 0.04631578947368421 chr21 38987524 38987748 chr21_ridge_80123_13 13 224 0.05803571428571429 chr21 38986697 38987039 chr21_ridge_80121_16 16 342 0.04678362573099415 chr21 38978974 38979146 chr21_ridge_80092_8 8 172 0.046511627906976744 chr21 38974595 38974704 chr21 ridge 80079 6 6 109 0.05504587155963303 chr21 38971681 38971885 chr21_ridge_80069_9 9 204 0.04411764705882353 chr21 38970745 38970851 chr21_ridge_80065_5 5 106 0.04716981132075472 chr21 38969417 38969922 chr21_ridge_80061_23 23 505 0.04554455445544554 chr21 38968315 38968486 chr21_ridge_80056_7 7 171 0.04093567251461988 chr21 38926462 38926834 chr21_ridge_79921_18 18 372 0.04838709677419355 chr21 38966222 38966620 chr21 ridge 80051 16 16 398 0.04020100502512563 chr21 38961105 38961182 chr21_ridge_80038_5 5 77 0.06493506493506493 chr21 38957232 38957332 chr21_ridge_80024_8 8 100 0.08 chr21 38957032 38957106 chr21_ridge_80023_5 5 74 0.06756756756756757 chr21 38954516 38954675 chr21_ridge_80013_8 8 159 0.050314465408805034 chr21 38954114 38954250 chr21_ridge_80011_7 7 136 0.051470588235294115 chr21 38948143 38948289 chr21_ridge_79994_6 6 146 0.0410958904109589 chr21 38946155 38946309 chr21_ridge_79988_7 7 154 0.045454545454545456 chr21 38941612 38941703 chr21_ridge_79971_5 5 91 0.054945054945054944 chr21 38937819 38937933 chr21_ridge_79957_9 9 114 0.07894736842105263 chr21 38935361 38937480 chr21_ridge_79955_lll 111 2119 0.052383199622463426 chr21 38931019 38931103 chr21_ridge_79935_6 6 84 0.07142857142857142 chr21 38963824 38964130 chr21_ridge_80043_17 17 306 0.05555555555555555 chr21 39344494 39344579 chr21_ridge_81298_5 5 85 0.058823529411764705 chr21 38361395 38363400 chr21_ridge_78193_143 143 2005 0.0713216957605985 chr21 38356727 38356851 chr21_ridge_78181_5 5 124 0.04032258064516129 chr21 37861842 37861899 chr21_ridge_76708_5 5 57 0.08771929824561403 chr21 37859057 37859191 chr21 ridge 76700 7 7 134 0.05223880597014925 chr21 37857070 37857261 chr21_ridge_76695_9 9 191 0.04712041884816754 chr21 37853809 37853926 chr21_ridge_76681_5 5 117 0.042735042735042736 chr21 37853474 37853617 chr21_ridge_76680_6 6 143 0.04195804195804196 chr21 37848796 37849044 chr21_ridge_76671_10 10 248 0.04032258064516129 chr21 37847915 37848015 chr21_ridge_76667_5 5 100 0.05 chr21 37842589 37842765 chr21 ridge 76651 9 9 176 0.05113636363636364 chr21 37839243 37839328 chr21_ridge_76640_5 5 85 0.058823529411764705 chr21 37837833 37837936 chr21_ridge_76635_5 5 103 0.04854368932038835 chr21 37834892 37835210 chr21_ridge_76629_13 13 318 0.040880503144654086 chr21 37833140 37834154 chr21_ridge_76627_56 56 1014 0.055226824457593686 chr21 37829379 37829518 chr21_ridge_76614_7 7 139 0.050359712230215826 chr21 37823216 37823478 chr21_ridge_76594_14 14 262 0.05343511450381679 chr21 37820730 37820982 chr21_ridge_76586_ll 11 252 0.04365079365079365 chr21 37815969 37816206 chr21_ridge_76573_13 13 237 0.05485232067510549 chr21 37815326 37815625 chr21_ridge_76572_16 16 299 0.05351170568561873Chr21 37813622 37813845 chr21_ridge_76566_9 9 223 0.04035874439461883 chr21 37810862 37811130 chr21_ridge_76557_13 13 268 0.048507462686567165 chr21 37799578 37799679 chr21_ridge_76528_5 5 101 0.04950495049504951 chr21 37797714 37797869 chr21_ridge_76520_7 7 155 0.04516129032258064 chr21 37792809 37793194 chr21_ridge_76509_17 17 385 0.04415584415584416 chr21 37792469 37792548 chr21_ridge_76508_7 7 79 0.08860759493670886 chr21 37862015 37862118 chr21_ridge_76709_5 5 103 0.04854368932038835 chr21 37863635 37863865 chr21_ridge_76715_ll 11 230 0.04782608695652174 chr21 37865902 37865987 chr21_ridge_76719_6 6 85 0.07058823529411765 chr21 37866359 37866555 chr21_ridge_76721_9 9 196 0.04591836734693878 chr21 37966804 37966842 chr21_ridge_77036_5 5 38 0.13157894736842105 chr21 37964771 37964851 chr21_ridge_77028_6 6 80 0.075 chr21 37959679 37959801 chr21_ridge_77017_6 6 122 0.04918032786885246 chr21 37948134 37948282 chr21_ridge_76977_8 8 148 0.05405405405405406 chr21 37945197 37945530 chr21_ridge_76970_15 15 333 0.04504504504504504 chr21 37943168 37943427 chr21_ridge_76964_ll 11 259 0.04247104247104247 chr21 37942293 37942401 chr21_ridge_76960_5 5 108 0.046296296296296294 chr21 37939171 37939481 chr21_ridge_76949_13 13 310 0.041935483870967745 chr21 37910081 37910167 chr21_ridge_76869_5 5 86 0.05813953488372093 chr21 37904997 37905086 chr21_ridge_76854_7 7 89 0.07865168539325842 chr21 37902168 37902402 chr21_ridge_76846_12 12 234 0.05128205128205128 chr21 37791641 37791972 chr21_ridge_76506_16 16 331 0.04833836858006042 chr21 37901177 37901231 chr21_ridge_76843_5 5 54 0.09259259259259259 chr21 37894656 37894991 chr21_ridge_76820_14 14 335 0.041791044776119404 chr21 37889213 37889429 chr21 ridge 76802 11 11 216 0.05092592592592592 chr21 37886115 37886236 chr21_ridge_76789_7 7 121 0.05785123966942149 chr21 37881860 37882184 chr21_ridge_76776_13 13 324 0.040123456790123455 chr21 37878967 37879061 chr21_ridge_76765_5 5 94 0.05319148936170213 chr21 37878807 37878849 chr21_ridge_76764_5 5 42 0.11904761904761904 chr21 37872974 37873359 chr21_ridge_76743_16 16 385 0.04155844155844156 chr21 37872442 37872806 chr21 ridge 76742 15 15 364 0.04120879120879121 chr21 37870516 37870619 chr21_ridge_76735_5 5 103 0.04854368932038835 chr21 37869867 37870173 chr21_ridge_76733_13 13 306 0.042483660130718956 chr21 37867549 37867612 chr21_ridge_76725_5 5 63 0.07936507936507936 chr21 37895241 37895300 chr21_ridge_76822_5 5 59 0.0847457627118644 chr21 37791005 37791133 chr21_ridge_76504_8 8 128 0.0625 chr21 37789428 37789494 chr21_ridge_76502_5 5 66 0.07575757575757576 chr21 37787998 37788760 chr21_ridge_76499_31 31 762 0.04068241469816273 chr21 37712345 37712562 chr21_ridge_76278_13 13 217 0.059907834101382486 chr21 37710099 37710203 chr21_ridge_76272_6 6 104 0.057692307692307696 chr21 37704551 37704793 chr21_ridge_76256_10 10 242 0.04132231404958678 chr21 37701187 37701579 chr21_ridge_76243_16 16 392 0.04081632653061224 chr21 37700361 37700466 chr21_ridge_76241_5 5 105 0.047619047619047616 chr21 37699019 37699407 chr21_ridge_76238_18 18 388 0.04639175257731959 chr21 37698235 37698302 chr21_ridge_76236_5 5 67 0.07462686567164178 chr21 37697152 37697298 chr21_ridge_76233_6 6 146 0.0410958904109589 chr21 37696604 37696879 chr21_ridge_76231_15 15 275 0.05454545454545454 chr21 37696193 37696468 chr21 ridge 76230 15 15 275 0.05454545454545454 chr21 37694730 37694830 chr21_ridge_76223_7 7 100 0.07 chr21 37712956 37713059 chr21_ridge_76281_7 7 103 0.06796116504854369 chr21 37691661 37693627 chr21_ridge_76218_140 140 1966 0.07121057985757884 chr21 37690498 37690829 chr21_ridge_76215_22 22 331 0.06646525679758308 chr21 37683638 37683838 chr21_ridge_76195_8 8 200 0.04 chr21 37682415 37682457 chr21 ridge 76192 5 5 42 0.11904761904761904 chr21 37681635 37681983 chr21_ridge_76190_26 26 348 0.07471264367816093 chr21 37679093 37679221 chr21_ridge_76181_6 6 128 0.046875 chr21 37678225 37678337 chr21_ridge_76179_6 6 112 0.05357142857142857 chr21 37676242 37676369 chr21_ridge_76174_6 6 127 0.047244094488188976 chr21 37671914 37671996 chr21_ridge_76163_6 6 82 0.07317073170731707 chr21 37670967 37671189 chr21_ridge_76159_10 10 222 0.04504504504504504 chr21 37667637 37668656 chr21_ridge_76150_63 63 1019 0.06182531894013739 chr21 37666719 37666790 chr21_ridge_76148_6 6 71 0.08450704225352113 chr21 37691451 37691559 chr21_ridge_76217_5 5 108 0.046296296296296294Chr21 37967494 37967566 chr21_ridge_77039_7 7 72 0.09722222222222222 chr21 37713716 37713798 chr21 ridge 76284 5 5 82 0.06097560975609756 chr21 37715540 37715687 chr21_ridge_76291_7 7 147 0.047619047619047616 chr21 37786248 37786423 chr21_ridge_76494_7 7 175 0.04 chr21 37784937 37785221 chr21_ridge_76491_12 12 284 0.04225352112676056 chr21 37774957 37775261 chr21_ridge_76466_14 14 304 0.046052631578947366 chr21 37772365 37772471 chr21_ridge_76460_7 7 106 0.0660377358490566 chr21 37772154 37772251 chr21_ridge_76459_5 5 97 0.05154639175257732 chr21 37765816 37766047 chr21_ridge_76444_10 10 231 0.04329004329004329 chr21 37764686 37765526 chr21_ridge_76442_61 61 840 0.07261904761904762 chr21 37762098 37762143 chr21_ridge_76433_5 5 45 0.1111111111111111 chr21 37760865 37761060 chr21_ridge_76428_9 9 195 0.046153846153846156 chr21 37759932 37760058 chr21_ridge_76426_7 7 126 0.05555555555555555 chr21 37757035 37759156 chr21_ridge_76423_116 116 2121 0.05469118340405469 chr21 37714352 37714561 chr21_ridge_76287_9 9 209 0.0430622009569378 chr21 37755923 37756241 chr21_ridge_76420_21 21 318 0.0660377358490566 chr21 37744139 37744256 chr21_ridge_76391_5 5 117 0.042735042735042736 chr21 37742992 37743127 chr21_ridge_76387_7 7 135 0.05185185185185185 chr21 37731014 37731268 chr21_ridge_76346_ll 11 254 0.04330708661417323 chr21 37730316 37730457 chr21_ridge_76343_7 7 141 0.04964539007092199 chr21 37726650 37726890 chr21_ridge_76331_10 10 240 0.041666666666666664 chr21 37722560 37722679 chr21_ridge_76315_9 9 119 0.07563025210084033 chr21 37721177 37721379 chr21_ridge_76310_10 10 202 0.04950495049504951 chr21 37718419 37718612 chr21_ridge_76300_10 10 193 0.05181347150259067 chr21 37717995 37718249 chr21 ridge 76299 12 12 254 0.047244094488188976 chr21 37717703 37717876 chr21_ridge_76298_7 7 173 0.04046242774566474 chr21 37716923 37716991 chr21_ridge_76296_5 5 68 0.07352941176470588 chr21 37749137 37749408 chr21_ridge_76405_12 12 271 0.04428044280442804 chr21 37973516 37973605 chr21_ridge_77058_6 6 89 0.06741573033707865 chr21 37983940 37984067 chr21_ridge_77091_7 7 127 0.05511811023622047 chr21 37990126 37990221 chr21 ridge 77108 5 5 95 0.05263157894736842 chr21 38254295 38254673 chr21_ridge_77877_19 19 378 0.05026455026455026 chr21 38252052 38252158 chr21_ridge_77871_5 5 106 0.04716981132075472 chr21 38247059 38247481 chr21_ridge_77858_17 17 422 0.04028436018957346 chr21 38246473 38246696 chr21_ridge_77856_ll 11 223 0.04932735426008968 chr21 38244446 38244677 chr21_ridge_77848_13 13 231 0.05627705627705628 chr21 38243310 38243406 chr21_ridge_77844_6 6 96 0.0625 chr21 38241453 38241783 chr21_ridge_77839_21 21 330 0.06363636363636363 chr21 38235161 38235344 chr21_ridge_77819_8 8 183 0.04371584699453552 chr21 38234912 38235042 chr21_ridge_77818_7 7 130 0.05384615384615385 chr21 38222858 38223010 chr21_ridge_77778_9 9 152 0.05921052631578947 chr21 38216425 38216675 chr21_ridge_77753_12 12 250 0.048 chr21 38258458 38258719 chr21_ridge_77888_16 16 261 0.06130268199233716 chr21 38215646 38215756 chr21_ridge_77750_6 6 110 0.05454545454545454 chr21 38209101 38209222 chr21_ridge_77731_5 5 121 0.04132231404958678 chr21 38208356 38208500 chr21_ridge_77728_7 7 144 0.04861111111111111 chr21 38206136 38206436 chr21_ridge_77721_13 13 300 0.043333333333333335 chr21 38204429 38204527 chr21_ridge_77715_5 5 98 0.05102040816326531 chr21 38202614 38202728 chr21_ridge_77709_5 5 114 0.043859649122807015 chr21 38202057 38202200 chr21_ridge_77707_9 9 143 0.06293706293706294 chr21 38194437 38194711 chr21_ridge_77684_ll 11 274 0.040145985401459854 chr21 38166333 38166450 chr21_ridge_77602_6 6 117 0.05128205128205128 chr21 38165827 38165892 chr21_ridge_77600_5 5 65 0.07692307692307693 chr21 38163992 38164145 chr21 ridge 77596 8 8 153 0.05228758169934641 chr21 38162910 38162987 chr21_ridge_77592_6 6 77 0.07792207792207792 chr21 38212971 38213069 chr21_ridge_77742_6 6 98 0.061224489795918366 chr21 38161082 38161184 chr21_ridge_77584_7 7 102 0.06862745098039216 chr21 38267255 38267608 chr21_ridge_77917_18 18 353 0.05099150141643059 chr21 38272677 38272877 chr21_ridge_77935_9 9 200 0.045 chr21 38352548 38353375 chr21_ridge_78170_56 56 827 0.06771463119709795 chr21 38344360 38344398 chr21_ridge_78146_5 5 38 0.13157894736842105 chr21 38342886 38343382 chr21_ridge_78143_21 21 496 0.04233870967741935 chr21 38342112 38342283 chr21_ridge_78140_8 8 171 0.04678362573099415Chr21 38341931 38341997 chr21_ridge_78139_5 5 66 0.07575757575757576 chr21 38338347 38339604 chr21 ridge 78132 135 135 1257 0.10739856801909307 chr21 38338121 38338210 chr21_ridge_78131_7 7 89 0.07865168539325842 chr21 38335906 38336006 chr21_ridge_78125_6 6 100 0.06 chr21 38333366 38333405 chr21_ridge_78113_5 5 39 0.1282051282051282 chr21 38329918 38330619 chr21_ridge_78104_35 35 701 0.04992867332382311 chr21 38326694 38326893 chr21_ridge_78095_10 10 199 0.05025125628140704 chr21 38270416 38270660 chr21_ridge_77929_10 10 244 0.040983606557377046 chr21 38324809 38325084 chr21_ridge_78088_12 12 275 0.04363636363636364 chr21 38304171 38304414 chr21_ridge_78028_10 10 243 0.0411522633744856 chr21 38302022 38302154 chr21_ridge_78021_6 6 132 0.045454545454545456 chr21 38296163 38296307 chr21_ridge_78002_7 7 144 0.04861111111111111 chr21 38295107 38295935 chr21_ridge_78001_36 36 828 0.043478260869565216 chr21 38288866 38288958 chr21_ridge_77982_5 5 92 0.05434782608695652 chr21 38288136 38288204 chr21_ridge_77980_6 6 68 0.08823529411764706 chr21 38287811 38288025 chr21_ridge_77979_9 9 214 0.04205607476635514 chr21 38287493 38287574 chr21_ridge_77977_5 5 81 0.06172839506172839 chr21 38286974 38287376 chr21_ridge_77976_17 17 402 0.04228855721393035 chr21 38283784 38284366 chr21_ridge_77967_24 24 582 0.041237113402061855 chr21 38274281 38274418 chr21_ridge_77938_6 6 137 0.043795620437956206 chr21 38308635 38308910 chr21_ridge_78042_ll 11 275 0.04 chr21 38357648 38358020 chr21_ridge_78182_17 17 372 0.0456989247311828 chr21 38159921 38160027 chr21_ridge_77581_6 6 106 0.05660377358490566 chr21 38150805 38150869 chr21_ridge_77556_5 5 64 0.078125 chr21 38083331 38083402 chr21_ridge_77359_5 5 71 0.07042253521126761 chr21 38082503 38083182 chr21_ridge_77358_36 36 679 0.053019145802650956 chr21 38079608 38082403 chr21_ridge_77357_196 196 2795 0.0701252236135957 chr21 38076506 38079502 chr21_ridge_77356_143 143 2996 0.04773030707610147 chr21 38074655 38074860 chr21_ridge_77350_9 9 205 0.04390243902439024 chr21 38072843 38074488 chr21_ridge_77349_114 114 1645 0.06930091185410335 chr21 38068192 38072553 chr21 ridge 77348 376 376 4361 0.08621875716578767 chr21 38064224 38067493 chr21_ridge_77346_188 188 3269 0.05750994187825023 chr21 38050654 38050798 chr21_ridge_77298_6 6 144 0.041666666666666664 chr21 38039289 38039530 chr21_ridge_77254_10 10 241 0.04149377593360996 chr21 38038264 38038399 chr21_ridge_77251_7 7 135 0.05185185185185185 chr21 38087141 38087163 chr21_ridge_77372_5 5 22 0.22727272727272727 chr21 38034392 38034482 chr21_ridge_77240_6 6 90 0.06666666666666667 chr21 38030290 38030414 chr21_ridge_77229_5 5 124 0.04032258064516129 chr21 38028675 38028728 chr21_ridge_77224_6 6 53 0.11320754716981132 chr21 38020185 38020315 chr21_ridge_77203_7 7 130 0.05384615384615385 chr21 38016184 38016471 chr21_ridge_77191_13 13 287 0.04529616724738676 chr21 38015278 38015317 chr21_ridge_77188_5 5 39 0.1282051282051282 chr21 38014163 38014279 chr21_ridge_77185_7 7 116 0.0603448275862069 chr21 38012909 38013334 chr21_ridge_77182_17 17 425 0.04 chr21 38004120 38004209 chr21_ridge_77151_6 6 89 0.06741573033707865 chr21 38003164 38003493 chr21_ridge_77148_14 14 329 0.0425531914893617 chr21 38001801 38002235 chr21_ridge_77145_20 20 434 0.04608294930875576 chr21 37996910 37997006 chr21 ridge 77129 5 5 96 0.052083333333333336 chr21 38032997 38033371 chr21_ridge_77237_16 16 374 0.0427807486631016 chr21 38159102 38159614 chr21_ridge_77579_21 21 512 0.041015625 chr21 38089785 38090066 chr21_ridge_77380_14 14 281 0.0498220640569395 chr21 38091980 38092275 chr21_ridge_77387_12 12 295 0.04067796610169491 chr21 38145005 38145174 chr21_ridge_77536_9 9 169 0.05325443786982249 chr21 38143212 38143515 chr21 ridge 77532 17 17 303 0.056105610561056105 chr21 38141248 38141389 chr21_ridge_77525_6 6 141 0.0425531914893617 chr21 38139526 38139654 chr21_ridge_77521_12 12 128 0.09375 chr21 38134638 38134823 chr21_ridge_77503_10 10 185 0.05405405405405406 chr21 38134084 38134305 chr21_ridge_77501_ll 11 221 0.049773755656108594 chr21 38133767 38133963 chr21_ridge_77500_8 8 196 0.04081632653061224 chr21 38132635 38132707 chr21_ridge_77497_5 5 72 0.06944444444444445 chr21 38130773 38130891 chr21_ridge_77491_5 5 118 0.0423728813559322 chr21 38128229 38128746 chr21_ridge_77483_23 23 517 0.04448742746615087 chr21 38126389 38126842 chr21_ridge_77478_24 24 453 0.052980132450331126Chr21 38091357 38091820 chr21_ridge_77386_20 20 463 0.04319654427645788 chr21 38119390 38120835 chr21_ridge_77464_151 151 1445 0.10449826989619378 chr21 38114358 38114463 chr21_ridge_77449_5 5 105 0.047619047619047616 chr21 38113837 38114221 chr21_ridge_77448_23 23 384 0.059895833333333336 chr21 38111152 38111282 chr21_ridge_77439_7 7 130 0.05384615384615385 chr21 38110029 38110211 chr21_ridge_77436_8 8 182 0.04395604395604396 chr21 38108895 38108943 chr21_ridge_77432_6 6 48 0.125 chr21 38107295 38107412 chr21_ridge_77427_7 7 117 0.05982905982905983 chr21 38104688 38104898 chr21_ridge_77420_12 12 210 0.05714285714285714 chr21 38103910 38104121 chr21_ridge_77418_9 9 211 0.04265402843601896 chr21 38102902 38103649 chr21_ridge_77416_34 34 747 0.04551539491298527 chr21 38101098 38101357 chr21_ridge_77412_ll 11 259 0.04247104247104247 chr21 38099776 38100018 chr21_ridge_77409_ll 11 242 0.045454545454545456 chr21 38116865 38117699 chr21_ridge_77455_35 35 834 0.04196642685851319 chr21 41490825 41490926 chr21_ridge_88248_5 5 101 0.04950495049504951 chr21 39345748 39345836 chr21_ridge_81304_5 5 88 0.056818181818181816 chr21 39353685 39354103 chr21_ridge_81328_22 22 418 0.05263157894736842 chr21 40744845 40745100 chr21_ridge_85847_17 17 255 0.06666666666666667 chr21 40744424 40744645 chr21_ridge_85846_ll 11 221 0.049773755656108594 chr21 40740082 40740539 chr21_ridge_85834_19 19 457 0.04157549234135667 chr21 40734909 40735370 chr21_ridge_85818_19 19 461 0.04121475054229935 chr21 40733624 40733753 chr21_ridge_85813_6 6 129 0.046511627906976744 chr21 40732103 40732329 chr21_ridge_85807_10 10 226 0.04424778761061947 chr21 40723620 40723989 chr21_ridge_85788_15 15 369 0.04065040650406504 chr21 40719610 40722206 chr21 ridge 85782 200 200 2596 0.07704160246533127 chr21 40715906 40716177 chr21_ridge_85770_ll 11 271 0.04059040590405904 chr21 40711956 40712261 chr21_ridge_85754_14 14 305 0.04590163934426229 chr21 40709803 40710237 chr21_ridge_85747_23 23 434 0.052995391705069124 chr21 40708988 40709474 chr21_ridge_85745_30 30 486 0.06172839506172839 chr21 40707475 40707900 chr21_ridge_85742_21 21 425 0.04941176470588235 chr21 40707259 40707306 chr21 ridge 85741 5 5 47 0.10638297872340426 chr21 40707038 40707141 chr21_ridge_85740_6 6 103 0.05825242718446602 chr21 40704754 40704870 chr21_ridge_85732_5 5 116 0.04310344827586207 chr21 40704541 40704630 chr21_ridge_85731_5 5 89 0.056179775280898875 chr21 40703346 40703671 chr21_ridge_85728_13 13 325 0.04 chr21 40696347 40696461 chr21_ridge_85703_6 6 114 0.05263157894736842 chr21 40695933 40696062 chr21_ridge_85702_8 8 129 0.06201550387596899 chr21 40688987 40689063 chr21_ridge_85680_6 6 76 0.07894736842105263 chr21 40686795 40687554 chr21_ridge_85675_32 32 759 0.04216073781291173 chr21 40684369 40686688 chr21_ridge_85674_252 252 2319 0.10866752910737387 chr21 40745745 40745858 chr21_ridge_85849_5 5 113 0.04424778761061947 chr21 40746294 40746428 chr21_ridge_85851_8 8 134 0.05970149253731343 chr21 40749956 40750131 chr21_ridge_85863_7 7 175 0.04 chr21 40751221 40751665 chr21_ridge_85866_24 24 444 0.05405405405405406 chr21 40857529 40857913 chr21_ridge_86188_23 23 384 0.059895833333333336 chr21 40850235 40850310 chr21_ridge_86162_5 5 75 0.06666666666666667 chr21 40841599 40841741 chr21_ridge_86136_6 6 142 0.04225352112676056 chr21 40830355 40830460 chr21 ridge 86105 5 5 105 0.047619047619047616 chr21 40829708 40829815 chr21_ridge_86102_5 5 107 0.04672897196261682 chr21 40823611 40823767 chr21_ridge_86084_7 7 156 0.04487179487179487 chr21 40822319 40822535 chr21_ridge_86078_9 9 216 0.041666666666666664 chr21 40816717 40818091 chr21_ridge_86063_99 99 1374 0.07205240174672489 chr21 40799208 40799544 chr21_ridge_86002_17 17 336 0.050595238095238096 chr21 40796029 40796127 chr21 ridge 85992 5 5 98 0.05102040816326531 chr21 40790570 40790677 chr21_ridge_85972_5 5 107 0.04672897196261682 chr21 40683459 40683563 chr21_ridge_85672_6 6 104 0.057692307692307696 chr21 40789720 40789990 chr21_ridge_85970_15 15 270 0.05555555555555555 chr21 40772107 40772137 chr21_ridge_85916_5 5 30 0.16666666666666666 chr21 40769032 40769115 chr21_ridge_85907_5 5 83 0.060240963855421686 chr21 40768760 40768900 chr21_ridge_85906_7 7 140 0.05 chr21 40767943 40768606 chr21_ridge_85905_31 31 663 0.04675716440422323 chr21 40762221 40762332 chr21_ridge_85887_5 5 111 0.04504504504504504 chr21 40759459 40760975 chr21_ridge_85883_70 70 1516 0.04617414248021108Chr21 40758861 40759069 chr21_ridge_85881_ll 11 208 0.052884615384615384 chr21 40756884 40758452 chr21 ridge 85878 76 76 1568 0.04846938775510204 chr21 40755853 40756003 chr21_ridge_85875_6 6 150 0.04 chr21 40753143 40753285 chr21_ridge_85868_9 9 142 0.06338028169014084 chr21 40751808 40753024 chr21_ridge_85867_75 75 1216 0.061677631578947366 chr21 40775063 40775973 chr21_ridge_85927_39 39 910 0.04285714285714286 chr21 40681385 40681745 chr21_ridge_85668_23 23 360 0.06388888888888888 chr21 40680810 40681077 chr21_ridge_85666_ll 11 267 0.04119850187265917 chr21 40677719 40677895 chr21_ridge_85657_8 8 176 0.045454545454545456 chr21 40577421 40577515 chr21_ridge_85325_5 5 94 0.05319148936170213 chr21 40575416 40575632 chr21_ridge_85318_13 13 216 0.06018518518518518 chr21 40572768 40572892 chr21_ridge_85307_6 6 124 0.04838709677419355 chr21 40567659 40567694 chr21_ridge_85290_5 5 35 0.14285714285714285 chr21 40554125 40556173 chr21_ridge_85257_151 151 2048 0.07373046875 chr21 40553900 40553995 chr21_ridge_85256_5 5 95 0.05263157894736842 chr21 40551217 40551308 chr21_ridge_85242_5 5 91 0.054945054945054944 chr21 40550388 40550521 chr21_ridge_85240_9 9 133 0.06766917293233082 chr21 40528464 40529728 chr21_ridge_85174_84 84 1264 0.06645569620253164 chr21 40521527 40521642 chr21_ridge_85153_6 6 115 0.05217391304347826 chr21 40515605 40515665 chr21_ridge_85134_5 5 60 0.08333333333333333 chr21 40579616 40579691 chr21_ridge_85333_5 5 75 0.06666666666666667 chr21 40510484 40511003 chr21_ridge_85115_26 26 519 0.05009633911368015 chr21 40506800 40507110 chr21_ridge_85103_15 15 310 0.04838709677419355 chr21 40506191 40506530 chr21_ridge_85101_16 16 339 0.0471976401179941 chr21 40499618 40499781 chr21 ridge 85080 7 7 163 0.04294478527607362 chr21 40480520 40480712 chr21_ridge_85024_10 10 192 0.052083333333333336 chr21 40480262 40480387 chr21_ridge_85023_7 7 125 0.056 chr21 40471793 40471907 chr21_ridge_84996_5 5 114 0.043859649122807015 chr21 40471455 40471481 chr21_ridge_84995_5 5 26 0.19230769230769232 chr21 40469199 40469359 chr21_ridge_84990_7 7 160 0.04375 chr21 40466169 40466278 chr21 ridge 84980 6 6 109 0.05504587155963303 chr21 40465371 40465818 chr21_ridge_84978_22 22 447 0.049217002237136466 chr21 40462865 40463161 chr21_ridge_84970_14 14 296 0.0472972972972973 chr21 40509631 40509702 chr21_ridge_85112_6 6 71 0.08450704225352113 chr21 40863131 40863370 chr21_ridge_86210_10 10 239 0.04184100418410042 chr21 40580602 40580714 chr21_ridge_85337_5 5 112 0.044642857142857144 chr21 40605665 40605910 chr21_ridge_85424_10 10 245 0.04081632653061224 chr21 40676305 40676414 chr21_ridge_85651_5 5 109 0.045871559633027525 chr21 40675791 40676023 chr21_ridge_85650_ll 11 232 0.04741379310344827 chr21 40667133 40667535 chr21_ridge_85621_20 20 402 0.04975124378109453 chr21 40665141 40665362 chr21_ridge_85616_9 9 221 0.04072398190045249 chr21 40661638 40661907 chr21_ridge_85605_19 19 269 0.07063197026022305 chr21 40658499 40658735 chr21_ridge_85592_ll 11 236 0.046610169491525424 chr21 40657969 40658310 chr21_ridge_85591_18 18 341 0.05278592375366569 chr21 40654755 40654880 chr21_ridge_85577_6 6 125 0.048 chr21 40653336 40653493 chr21_ridge_85574_7 7 157 0.044585987261146494 chr21 40649709 40649813 chr21_ridge_85562_5 5 104 0.04807692307692308 chr21 40646093 40646258 chr21 ridge 85550 7 7 165 0.04242424242424243 chr21 40586820 40587092 chr21_ridge_85358_12 12 272 0.04411764705882353 chr21 40644277 40644431 chr21_ridge_85544_8 8 154 0.05194805194805195 chr21 40639285 40639507 chr21_ridge_85530_15 15 222 0.06756756756756757 chr21 40637990 40638148 chr21_ridge_85526_7 7 158 0.04430379746835443 chr21 40637205 40637274 chr21_ridge_85524_6 6 69 0.08695652173913043 chr21 40634563 40634634 chr21 ridge 85516 5 5 71 0.07042253521126761 chr21 40634366 40634438 chr21_ridge_85515_5 5 72 0.06944444444444445 chr21 40627608 40627703 chr21_ridge_85495_7 7 95 0.07368421052631578 chr21 40619668 40619842 chr21_ridge_85473_8 8 174 0.04597701149425287 chr21 40618894 40619054 chr21_ridge_85471_9 9 160 0.05625 chr21 40618720 40618774 chr21_ridge_85470_5 5 54 0.09259259259259259 chr21 40615959 40616058 chr21_ridge_85460_5 5 99 0.050505050505050504 chr21 40612893 40612983 chr21_ridge_85448_5 5 90 0.05555555555555555 chr21 40642880 40643047 chr21_ridge_85541_7 7 167 0.041916167664670656 chr21 40868061 40868427 chr21_ridge_86225_23 23 366 0.06284153005464481Chr21 40870529 40870645 chr21_ridge_86231_5 5 116 0.04310344827586207 chr21 40881890 40882160 chr21 ridge 86274 22 22 270 0.08148148148148149 chr21 41297937 41298104 chr21_ridge_87607_7 7 167 0.041916167664670656 chr21 41297372 41297683 chr21_ridge_87606_15 15 311 0.04823151125401929 chr21 41282230 41282320 chr21_ridge_87554_5 5 90 0.05555555555555555 chr21 41281748 41282129 chr21_ridge_87553_17 17 381 0.04461942257217848 chr21 41281525 41281609 chr21_ridge_87552_6 6 84 0.07142857142857142 chr21 41275517 41275787 chr21_ridge_87535_21 21 270 0.07777777777777778 chr21 41266820 41266933 chr21_ridge_87509_5 5 113 0.04424778761061947 chr21 41253451 41253776 chr21_ridge_87469_13 13 325 0.04 chr21 41246734 41246906 chr21_ridge_87448_7 7 172 0.040697674418604654 chr21 41225713 41225834 chr21_ridge_87391_5 5 121 0.04132231404958678 chr21 41224826 41224959 chr21_ridge_87389_6 6 133 0.045112781954887216 chr21 41305593 41305721 chr21_ridge_87631_6 6 128 0.046875 chr21 41218174 41218296 chr21_ridge_87365_5 5 122 0.040983606557377046 chr21 41183187 41183253 chr21_ridge_87250_5 5 66 0.07575757575757576 chr21 41171171 41171343 chr21_ridge_87204_8 8 172 0.046511627906976744 chr21 41170337 41170428 chr21_ridge_87200_5 5 91 0.054945054945054944 chr21 41167531 41167756 chr21_ridge_87194_10 10 225 0 . 044444444444444446 chr21 41163763 41163856 chr21_ridge_87180_5 5 93 0.053763440860215055 chr21 41161008 41161096 chr21_ridge_87170_5 5 88 0.056818181818181816 chr21 41160436 41160605 chr21_ridge_87168_9 9 169 0.05325443786982249 chr21 41151060 41151202 chr21_ridge_87138_10 10 142 0.07042253521126761 chr21 41142386 41142475 chr21_ridge_87109_5 5 89 0.056179775280898875 chr21 41134992 41135097 chr21 ridge 87086 5 5 105 0.047619047619047616 chr21 41128973 41129082 chr21_ridge_87071_5 5 109 0.045871559633027525 chr21 41217684 41217827 chr21_ridge_87363_7 7 143 0.04895104895104895 chr21 41123795 41123905 chr21_ridge_87063_6 6 110 0.05454545454545454 chr21 41323523 41323642 chr21_ridge_87687_6 6 119 0.05042016806722689 chr21 41338998 41339064 chr21_ridge_87737_5 5 66 0.07575757575757576 chr21 41488549 41488883 chr21 ridge 88241 16 16 334 0.04790419161676647 chr21 41481376 41481678 chr21_ridge_88217_15 15 302 0.04966887417218543 chr21 41465000 41465125 chr21_ridge_88159_6 6 125 0.048 chr21 41457596 41457703 chr21_ridge_88135_9 9 107 0.08411214953271028 chr21 41451660 41451834 chr21_ridge_88117_7 7 174 0.040229885057471264 chr21 41450446 41450679 chr21_ridge_88112_12 12 233 0.05150214592274678 chr21 41446931 41447224 chr21_ridge_88101_14 14 293 0.04778156996587031 chr21 41445059 41445192 chr21_ridge_88093_7 7 133 0.05263157894736842 chr21 41444258 41444630 chr21_ridge_88091_16 16 372 0.043010752688172046 chr21 41432473 41432589 chr21_ridge_88054_6 6 116 0.05172413793103448 chr21 41427663 41427756 chr21_ridge_88036_5 5 93 0.053763440860215055 chr21 41334518 41334649 chr21_ridge_87720_6 6 131 0.04580152671755725 chr21 41423884 41424068 chr21_ridge_88023_ll 11 184 0.059782608695652176 chr21 41405107 41405580 chr21_ridge_87959_25 25 473 0.052854122621564484 chr21 41400308 41400768 chr21_ridge_87946_25 25 460 0.05434782608695652 chr21 41393090 41393178 chr21_ridge_87917_6 6 88 0.06818181818181818 chr21 41389525 41389768 chr21_ridge_87906_10 10 243 0.0411522633744856 chr21 41386385 41386602 chr21 ridge 87893 10 10 217 0.04608294930875576 chr21 41385993 41386088 chr21_ridge_87891_5 5 95 0.05263157894736842 chr21 41376854 41377112 chr21_ridge_87865_15 15 258 0.05813953488372093 chr21 41357554 41357618 chr21_ridge_87795_5 5 64 0.078125 chr21 41356545 41356703 chr21_ridge_87791_9 9 158 0.056962025316455694 chr21 41356235 41356445 chr21_ridge_87790_9 9 210 0.04285714285714286 chr21 41345126 41345294 chr21 ridge 87756 9 9 168 0.05357142857142857 chr21 41416263 41416415 chr21_ridge_87995_7 7 152 0.046052631578947366 chr21 40461370 40461537 chr21_ridge_84965_10 10 167 0.059880239520958084 chr21 41117694 41118260 chr21_ridge_87044_23 23 566 0.04063604240282685 chr21 41116006 41116162 chr21_ridge_87038_7 7 156 0.04487179487179487 chr21 41001088 41001266 chr21_ridge_86666_8 8 178 0.0449438202247191 chr21 40997222 40997425 chr21_ridge_86652_9 9 203 0.04433497536945813 chr21 40986242 40986355 chr21_ridge_86615_6 6 113 0.05309734513274336 chr21 40984134 40985692 chr21_ridge_86613_115 115 1558 0.07381258023106547 chr21 40976996 40977149 chr21_ridge_86593_10 10 153 0.06535947712418301Chr21 40976262 40976726 chr21_ridge_86591_22 22 464 0.04741379310344827 chr21 40973306 40973475 chr21 ridge 86581 11 11 169 0.0650887573964497 chr21 40971970 40972092 chr21_ridge_86576_5 5 122 0 . 040983606557377046 chr21 40966548 40966632 chr21_ridge_86555_5 5 84 0.05952380952380952 chr21 40959278 40959396 chr21_ridge_86532_5 5 118 0.0423728813559322 chr21 40950152 40950308 chr21_ridge_86503_7 7 156 0 . 04487179487179487 chr21 41003873 41003989 chr21_ridge_86674_5 5 116 0.04310344827586207 chr21 40944667 40944769 chr21_ridge_86484_5 5 102 0.049019607843137254 chr21 40938208 40938359 chr21_ridge_86465_8 8 151 0.052980132450331126 chr21 40930691 40930861 chr21_ridge_86438_7 7 170 0 . 041176470588235294 chr21 40928538 40928650 chr21_ridge_86429_5 5 112 0 . 044642857142857144 chr21 40927151 40927511 chr21_ridge_86424_17 17 360 0.04722222222222222 chr21 40913303 40913438 chr21_ridge_86375_6 6 135 0 . 044444444444444446 chr21 40904350 40904486 chr21_ridge_86343_8 8 136 0.058823529411764705 chr21 40902635 40902765 chr21_ridge_86337_9 9 130 0.06923076923076923 chr21 40896830 40896890 chr21_ridge_86317_5 5 60 0.08333333333333333 chr21 40891052 40891653 chr21_ridge_86301_25 25 601 0.04159733777038269 chr21 40887492 40887648 chr21_ridge_86291_7 7 156 0 . 04487179487179487 chr21 40884236 40884307 chr21_ridge_86279_5 5 71 0.07042253521126761 chr21 40939293 40939525 chr21_ridge_86470_12 12 232 0.05172413793103448 chr21 41117414 41117538 chr21_ridge_87043_7 7 124 0.056451612903225805 chr21 41006708 41006876 chr21_ridge_86683_7 7 168 0 . 041666666666666664 chr21 41016461 41016597 chr21_ridge_86716_7 7 136 0 . 051470588235294115 chr21 41114278 41114426 chr21_ridge_87029_6 6 148 0.04054054054054054 chr21 41111535 41111700 chr21 ridge 87018 7 7 165 0.04242424242424243 chr21 41106087 41106298 chr21_ridge_87000_9 9 211 0.04265402843601896 chr21 41103159 41103274 chr21_ridge_86989_5 5 115 0 . 043478260869565216 chr21 41100509 41100633 chr21_ridge_86979_5 5 124 0.04032258064516129 chr21 41088024 41088146 chr21_ridge_86939_6 6 122 0.04918032786885246 chr21 41085909 41086057 chr21_ridge_86931_7 7 148 0.0472972972972973 chr21 41084186 41084322 chr21 ridge 86925 7 7 136 0.051470588235294115 chr21 41082965 41083087 chr21_ridge_86922_6 6 122 0.04918032786885246 chr21 41072896 41073019 chr21_ridge_86894_6 6 123 0 . 04878048780487805 chr21 41070019 41070103 chr21_ridge_86882_5 5 84 0.05952380952380952 chr21 41010230 41010390 chr21_ridge_86694_ll 11 160 0.06875 chr21 41069460 41069570 chr21_ridge_86880_5 5 110 0 . 045454545454545456 chr21 41046912 41047092 chr21_ridge_86805_9 9 180 0.05 chr21 41046520 41046763 chr21_ridge_86804_10 10 243 0.0411522633744856 chr21 41041663 41041765 chr21_ridge_86787_6 6 102 0 . 058823529411764705 chr21 41039725 41039782 chr21_ridge_86781_5 5 57 0.08771929824561403 chr21 41033101 41033615 chr21_ridge_86767_25 25 514 0 . 048638132295719845 chr21 41031848 41031925 chr21_ridge_86762_5 5 77 0.06493506493506493 chr21 41023633 41023747 chr21_ridge_86741_5 5 114 0.043859649122807015 chr21 41022491 41022682 chr21_ridge_86737_9 9 191 0 . 04712041884816754 chr21 41022246 41022367 chr21_ridge_86736_5 5 121 0.04132231404958678 chr21 41021896 41022044 chr21_ridge_86735_6 6 148 0 . 04054054054054054 chr21 41020728 41020963 chr21_ridge_86732_10 10 235 0.0425531914893617 chr21 41063694 41063987 chr21 ridge 86856 13 13 293 0.04436860068259386 chr21 39350814 39350917 chr21_ridge_81318_6 6 103 0.05825242718446602 chr21 40459271 40459560 chr21_ridge_84961_15 15 289 0.05190311418685121 chr21 40453268 40453564 chr21_ridge_84943_13 13 296 0.04391891891891892 chr21 39817295 39817512 chr21_ridge_82851_12 12 217 0.055299539170506916 chr21 39815325 39815379 chr21_ridge_82845_5 5 54 0.09259259259259259 chr21 39814767 39815213 chr21 ridge 82844 19 19 446 0 . 042600896860986545 chr21 39814372 39814471 chr21_ridge_82842_5 5 99 0.050505050505050504 chr21 39812175 39812660 chr21_ridge_82836_20 20 485 0 . 041237113402061855 chr21 39810489 39810937 chr21_ridge_82831_19 19 448 0.04241071428571429 chr21 39807962 39808153 chr21_ridge_82822_8 8 191 0 . 041884816753926704 chr21 39800284 39800405 chr21_ridge_82797_8 8 121 0.06611570247933884 chr21 39798470 39798808 chr21_ridge_82791_15 15 338 0.04437869822485207 chr21 39796498 39796590 chr21_ridge_82782_6 6 92 0.06521739130434782 chr21 39790572 39790721 chr21_ridge_82760_7 7 149 0.04697986577181208 chr21 39788755 39788899 chr21_ridge_82755_10 10 144 0 . 06944444444444445Chr21 39784753 39784841 chr21_ridge_82745_5 5 88 0.056818181818181816 chr21 39777798 39778173 chr21 ridge 82727 15 15 375 0.04 chr21 39776314 39776512 chr21_ridge_82720_9 9 198 0 . 045454545454545456 chr21 39767820 39767904 chr21_ridge_82697_5 5 84 0.05952380952380952 chr21 39766445 39766565 chr21_ridge_82692_8 8 120 0.06666666666666667 chr21 39756818 39756887 chr21_ridge_82655_5 5 69 0.07246376811594203 chr21 39755445 39756439 chr21_ridge_82653_46 46 994 0.04627766599597585 chr21 39754067 39754251 chr21_ridge_82649_10 10 184 0.05434782608695652 chr21 39748211 39748378 chr21_ridge_82630_10 10 167 0 . 059880239520958084 chr21 39727880 39728269 chr21_ridge_82564_20 20 389 0.05141388174807198 chr21 39726184 39726379 chr21_ridge_82558_10 10 195 0.05128205128205128 chr21 39822034 39822274 chr21_ridge_82866_10 10 240 0 . 041666666666666664 chr21 39825719 39825768 chr21_ridge_82880_5 5 49 0.10204081632653061 chr21 39840587 39840864 chr21_ridge_82927_17 17 277 0.061371841155234655 chr21 39844262 39844765 chr21_ridge_82943_21 21 503 0 . 041749502982107355 chr21 39959209 39959571 chr21_ridge_83327_21 21 362 0 . 058011049723756904 chr21 39953509 39953953 chr21_ridge_83304_20 20 444 0 . 04504504504504504 chr21 39951562 39952156 chr21_ridge_83299_28 28 594 0 . 04713804713804714 chr21 39949984 39950084 chr21_ridge_83291_6 6 100 0.06 chr21 39941152 39941261 chr21_ridge_83260_5 5 109 0.045871559633027525 chr21 39939652 39940017 chr21_ridge_83255_18 18 365 0 . 049315068493150684 chr21 39935783 39935881 chr21_ridge_83240_6 6 98 0 . 061224489795918366 chr21 39916185 39916372 chr21_ridge_83183_8 8 187 0.0427807486631016 chr21 39901612 39901717 chr21_ridge_83129_5 5 105 0 . 047619047619047616 chr21 39900301 39900667 chr21 ridge 83125 20 20 366 0.0546448087431694 chr21 39899710 39899905 chr21_ridge_83123_8 8 195 0.041025641025641026 chr21 39723263 39723510 chr21_ridge_82549_13 13 247 0.05263157894736842 chr21 39878626 39879257 chr21_ridge_83054_28 28 631 0 . 044374009508716325 chr21 39873012 39873330 chr21_ridge_83038_17 17 318 0.05345911949685535 chr21 39872175 39872276 chr21_ridge_83035_7 7 101 0.06930693069306931 chr21 39865787 39866084 chr21 ridge 83011 13 13 297 0.04377104377104377 chr21 39865555 39865656 chr21_ridge_83010_6 6 101 0.0594059405940594 chr21 39860929 39861032 chr21_ridge_82994_6 6 103 0.05825242718446602 chr21 39860686 39860821 chr21_ridge_82993_6 6 135 0 . 044444444444444446 chr21 39857412 39857672 chr21_ridge_82980_ll 11 260 0.04230769230769231 chr21 39856020 39856187 chr21_ridge_82975_8 8 167 0.04790419161676647 chr21 39847243 39847334 chr21_ridge_82953_5 5 91 0 . 054945054945054944 chr21 39845746 39845806 chr21_ridge_82947_6 6 60 0.1 chr21 39844867 39845115 chr21_ridge_82944_12 12 248 0.04838709677419355 chr21 39875326 39875542 chr21_ridge_83044_9 9 216 0 . 041666666666666664 chr21 39722367 39722505 chr21_ridge_82545_6 6 138 0 . 043478260869565216 chr21 39708585 39708699 chr21_ridge_82495_5 5 114 0.043859649122807015 chr21 39690983 39691220 chr21_ridge_82434_10 10 237 0.04219409282700422 chr21 39493132 39493629 chr21_ridge_81799_23 23 497 0.04627766599597585 chr21 39491184 39491501 chr21_ridge_81792_15 15 317 0.0473186119873817 chr21 39490916 39491058 chr21_ridge_81791_7 7 142 0.04929577464788732 chr21 39484845 39485221 chr21_ridge_81772_18 18 376 0.047872340425531915 chr21 39480699 39480946 chr21 ridge 81762 11 11 247 0.044534412955465584 chr21 39475728 39475814 chr21_ridge_81745_7 7 86 0.08139534883720931 chr21 39470659 39470783 chr21_ridge_81728_5 5 124 0.04032258064516129 chr21 39464242 39464387 chr21_ridge_81706_6 6 145 0 . 041379310344827586 chr21 39463395 39463513 chr21_ridge_81703_5 5 118 0.0423728813559322 chr21 39461883 39462056 chr21_ridge_81697_7 7 173 0.04046242774566474 chr21 39461603 39461712 chr21 ridge 81696 7 7 109 0.06422018348623854 chr21 39493729 39493966 chr21_ridge_81800_ll 11 237 0 . 046413502109704644 chr21 39461242 39461367 chr21_ridge_81694_6 6 125 0.048 chr21 39452668 39452799 chr21_ridge_81669_6 6 131 0.04580152671755725 chr21 39448309 39448490 chr21_ridge_81655_10 10 181 0 . 055248618784530384 chr21 39411680 39411810 chr21_ridge_81528_6 6 130 0.046153846153846156 chr21 39402991 39403314 chr21_ridge_81499_19 19 323 0.058823529411764705 chr21 39399051 39399177 chr21_ridge_81486_6 6 126 0 . 047619047619047616 chr21 39397923 39398313 chr21_ridge_81483_23 23 390 0.05897435897435897 chr21 39395045 39395096 chr21_ridge_81471_5 5 51 0.09803921568627451Chr21 39383927 39384369 chr21_ridge_81431_19 19 442 0.042986425339366516 chr21 39372500 39372633 chr21 ridge 81395 6 6 133 0.045112781954887216 chr21 39369718 39369790 chr21_ridge_81386_7 7 72 0.09722222222222222 chr21 39366536 39366644 chr21_ridge_81372_5 5 108 0 . 046296296296296294 chr21 39454093 39454239 chr21_ridge_81672_7 7 146 0.04794520547945205 chr21 39971529 39971599 chr21_ridge_83367_5 5 70 0.07142857142857142 chr21 39496735 39496815 chr21_ridge_81810_5 5 80 0.0625 chr21 39499434 39499568 chr21_ridge_81820_6 6 134 0.04477611940298507 chr21 39690039 39690219 chr21_ridge_82432_12 12 180 0.06666666666666667 chr21 39683145 39683291 chr21_ridge_82410_6 6 146 0.0410958904109589 chr21 39681990 39682167 chr21_ridge_82405_9 9 177 0.05084745762711865 chr21 39676626 39677051 chr21_ridge_82388_24 24 425 0.05647058823529412 chr21 39673784 39673997 chr21_ridge_82374_14 14 213 0.06572769953051644 chr21 39662142 39662248 chr21_ridge_82333_6 6 106 0.05660377358490566 chr21 39660053 39660291 chr21_ridge_82327_13 13 238 0.0546218487394958 chr21 39654792 39654866 chr21_ridge_82314_5 5 74 0.06756756756756757 chr21 39651001 39651098 chr21_ridge_82303_5 5 97 0.05154639175257732 chr21 39649453 39649547 chr21_ridge_82296_5 5 94 0.05319148936170213 chr21 39644214 39644354 chr21_ridge_82276_6 6 140 0.04285714285714286 chr21 39498407 39498575 chr21_ridge_81816_8 8 168 0 . 047619047619047616 chr21 39632546 39632634 chr21_ridge_82231_6 6 88 0.06818181818181818 chr21 39615297 39615412 chr21_ridge_82177_5 5 115 0 . 043478260869565216 chr21 39613961 39614070 chr21_ridge_82172_5 5 109 0.045871559633027525 chr21 39613342 39613417 chr21_ridge_82170_5 5 75 0.06666666666666667 chr21 39607239 39607430 chr21 ridge 82150 8 8 191 0 . 041884816753926704 chr21 39601112 39601220 chr21_ridge_82134_5 5 108 0 . 046296296296296294 chr21 39595938 39596039 chr21_ridge_82116_5 5 101 0.04950495049504951 chr21 39590593 39590869 chr21_ridge_82101_24 24 276 0.08695652173913043 chr21 39585022 39585107 chr21_ridge_82081_5 5 85 0 . 058823529411764705 chr21 39579000 39579092 chr21_ridge_82061_6 6 92 0.06521739130434782 chr21 39544791 39545021 chr21 ridge 81967 13 13 230 0.05652173913043478 chr21 39509240 39509485 chr21_ridge_81850_14 14 245 0.05714285714285714 chr21 39615530 39615623 chr21_ridge_82178_5 5 93 0 . 053763440860215055 chr21 39973015 39973122 chr21_ridge_83373_5 5 107 0.04672897196261682 chr21 39975843 39976172 chr21_ridge_83382_22 22 329 0.0668693009118541 chr21 39979239 39979557 chr21_ridge_83392_13 13 318 0 . 040880503144654086 chr21 40345983 40346149 chr21_ridge_84597_7 7 166 0.04216867469879518 chr21 40344318 40344843 chr21_ridge_84592_28 28 525 0.05333333333333334 chr21 40340980 40341104 chr21_ridge_84580_7 7 124 0.056451612903225805 chr21 40328306 40328431 chr21_ridge_84542_5 5 125 0.04 chr21 40321456 40321619 chr21_ridge_84516_7 7 163 0.04294478527607362 chr21 40320597 40320717 chr21_ridge_84514_5 5 120 0 . 041666666666666664 chr21 40317921 40318045 chr21_ridge_84504_9 9 124 0.07258064516129033 chr21 40317595 40317821 chr21_ridge_84503_10 10 226 0 . 04424778761061947 chr21 40316680 40317447 chr21_ridge_84502_31 31 767 0.04041720990873533 chr21 40314551 40314676 chr21_ridge_84495_5 5 125 0.04 chr21 40312351 40312395 chr21_ridge_84485_5 5 44 0.11363636363636363 chr21 40347346 40347521 chr21 ridge 84603 7 7 175 0.04 chr21 40310497 40310654 chr21_ridge_84477_7 7 157 0 . 044585987261146494 chr21 40300206 40300313 chr21_ridge_84446_5 5 107 0.04672897196261682 chr21 40290027 40290113 chr21_ridge_84404_7 7 86 0.08139534883720931 chr21 40284821 40285631 chr21_ridge_84393_40 40 810 0.04938271604938271 chr21 40281350 40281566 chr21_ridge_84381_10 10 216 0 . 046296296296296294 chr21 40278056 40278885 chr21 ridge 84371 35 35 829 0.04221954161640531 chr21 40277611 40277790 chr21_ridge_84369_8 8 179 0.0446927374301676 chr21 40246266 40246591 chr21_ridge_84272_24 24 325 0.07384615384615385 chr21 40244665 40244834 chr21_ridge_84267_7 7 169 0.04142011834319527 chr21 40239262 40239324 chr21_ridge_84248_6 6 62 0.0967741935483871 chr21 40233095 40233201 chr21_ridge_84225_6 6 106 0.05660377358490566 chr21 40219704 40219823 chr21_ridge_84177_8 8 119 0.06722689075630252 chr21 40305000 40305102 chr21_ridge_84459_5 5 102 0 . 049019607843137254 chr21 40208303 40208677 chr21_ridge_84138_23 23 374 0.06149732620320856 chr21 40349021 40349168 chr21_ridge_84609_6 6 147 0.04081632653061224Chr21 40354402 40355073 chr21_ridge_84626_32 32 671 0.04769001490312966 chr21 40452673 40452754 chr21 ridge 84940 5 5 81 0.06172839506172839 chr21 40447931 40448101 chr21_ridge_84928_9 9 170 0.052941176470588235 chr21 40434475 40434962 chr21_ridge_84885_20 20 487 0.04106776180698152 chr21 40432034 40432089 chr21_ridge_84879_5 5 55 0.09090909090909091 chr21 40421735 40421841 chr21_ridge_84845_6 6 106 0.05660377358490566 chr21 40418387 40418550 chr21_ridge_84835_8 8 163 0.049079754601226995 chr21 40403143 40403273 chr21_ridge_84784_9 9 130 0.06923076923076923 chr21 40402399 40402527 chr21_ridge_84781_6 6 128 0.046875 chr21 40398002 40398279 chr21_ridge_84764_12 12 277 0.04332129963898917 chr21 40395064 40395765 chr21_ridge_84754_29 29 701 0.04136947218259629 chr21 40393483 40393618 chr21_ridge_84749_6 6 135 0 . 044444444444444446 chr21 40353121 40353411 chr21_ridge_84623_12 12 290 0.041379310344827586 chr21 40393178 40393373 chr21_ridge_84748_9 9 195 0.046153846153846156 chr21 40390848 40390957 chr21_ridge_84738_5 5 109 0.045871559633027525 chr21 40383633 40383814 chr21_ridge_84716_8 8 181 0.04419889502762431 chr21 40383006 40383277 chr21_ridge_84714_ll 11 271 0.04059040590405904 chr21 40380740 40380905 chr21_ridge_84709_7 7 165 0.04242424242424243 chr21 40377274 40377384 chr21_ridge_84696_7 7 110 0.06363636363636363 chr21 40376671 40377053 chr21_ridge_84695_16 16 382 0.041884816753926704 chr21 40374119 40374284 chr21_ridge_84686_9 9 165 0.05454545454545454 chr21 40372070 40372208 chr21_ridge_84677_6 6 138 0.043478260869565216 chr21 40360946 40361754 chr21_ridge_84646_36 36 808 0.04455445544554455 chr21 40360051 40360133 chr21_ridge_84643_5 5 82 0.06097560975609756 chr21 40356067 40356174 chr21 ridge 84629 5 5 107 0.04672897196261682 chr21 40392216 40392299 chr21_ridge_84745_5 5 83 0.060240963855421686 chr21 40456461 40456653 chr21_ridge_84951_10 10 192 0.052083333333333336 chr21 40200057 40200154 chr21_ridge_84109_5 5 97 0.05154639175257732 chr21 40193485 40193622 chr21_ridge_84092_6 6 137 0.043795620437956206 chr21 40089472 40089616 chr21_ridge_83771_7 7 144 0.04861111111111111 chr21 40084972 40085081 chr21 ridge 83751 5 5 109 0.045871559633027525 chr21 40075615 40075809 chr21_ridge_83719_8 8 194 0.041237113402061855 chr21 40074989 40075235 chr21_ridge_83717_15 15 246 0.06097560975609756 chr21 40067217 40067279 chr21_ridge_83685_5 5 62 0.08064516129032258 chr21 40060197 40060310 chr21_ridge_83666_5 5 113 0.04424778761061947 chr21 40049445 40049815 chr21_ridge_83631_19 19 370 0.051351351351351354 chr21 40049288 40049334 chr21_ridge_83630_5 5 46 0.10869565217391304 chr21 40047255 40047730 chr21_ridge_83624_24 24 475 0.05052631578947368 chr21 40043979 40044076 chr21_ridge_83613_5 5 97 0.05154639175257732 chr21 40042712 40042973 chr21_ridge_83608_12 12 261 0.04597701149425287 chr21 40090005 40090265 chr21_ridge_83773_14 14 260 0.05384615384615385 chr21 40040831 40040945 chr21_ridge_83601_5 5 114 0.043859649122807015 chr21 40031968 40033988 chr21_ridge_83573_197 197 2020 0.09752475247524753 chr21 40025599 40025674 chr21_ridge_83552_5 5 75 0.06666666666666667 chr21 40023632 40023745 chr21_ridge_83546_6 6 113 0.05309734513274336 chr21 40020511 40020634 chr21_ridge_83538_5 5 123 0.04065040650406504 chr21 40015502 40015609 chr21_ridge_83522_5 5 107 0.04672897196261682 chr21 40009945 40010067 chr21 ridge 83500 6 6 122 0.04918032786885246 chr21 40006207 40006367 chr21_ridge_83485_9 9 160 0.05625 chr21 39994138 39994246 chr21_ridge_83443_7 7 108 0.06481481481481481 chr21 39983995 39984087 chr21_ridge_83408_6 6 92 0.06521739130434782 chr21 39983032 39983110 chr21_ridge_83404_5 5 78 0.0641025641025641 chr21 39982434 39982454 chr21_ridge_83402_8 8 20 0.4 chr21 40038541 40038884 chr21 ridge 83592 25 25 343 0.0728862973760933 chr21 40194465 40195187 chr21_ridge_84096_36 36 722 0.04986149584487535 chr21 40092156 40092184 chr21_ridge_83779_5 5 28 0.17857142857142858 chr21 40099500 40099710 chr21_ridge_83805_9 9 210 0.04285714285714286 chr21 40192377 40192474 chr21_ridge_84089_6 6 97 0.061855670103092786 chr21 40191364 40191557 chr21_ridge_84086_9 9 193 0.046632124352331605 chr21 40190986 40191051 chr21_ridge_84084_5 5 65 0.07692307692307693 chr21 40190219 40190503 chr21_ridge_84082_12 12 284 0.04225352112676056 chr21 40182428 40182546 chr21_ridge_84055_5 5 118 0.0423728813559322 chr21 40176860 40179152 chr21_ridge_84043_181 181 2292 0.07897033158813263Chr21 40176504 40176743 chr21_ridge_84042_ll 11 239 0.04602510460251046 chr21 40175556 40175705 chr21 ridge 84038 8 8 149 0.053691275167785234 chr21 40170875 40170985 chr21_ridge_84021_6 6 110 0.05454545454545454 chr21 40170304 40170448 chr21_ridge_84019_6 6 144 0.041666666666666664 chr21 40168956 40169039 chr21_ridge_84014_6 6 83 0.07228915662650602 chr21 40094253 40094335 chr21_ridge_83788_5 5 82 0.06097560975609756 chr21 40151339 40151439 chr21_ridge_83960_5 5 100 0.05 chr21 40141464 40141591 chr21_ridge_83932_6 6 127 0.047244094488188976 chr21 40135023 40135196 chr21_ridge_83910_7 7 173 0.04046242774566474 chr21 40134059 40134241 chr21_ridge_83908_14 14 182 0.07692307692307693 chr21 40132937 40133026 chr21_ridge_83904_5 5 89 0.056179775280898875 chr21 40130831 40130921 chr21_ridge_83897_5 5 90 0.05555555555555555 chr21 40128347 40128702 chr21_ridge_83889_20 20 355 0.056338028169014086 chr21 40124790 40125002 chr21_ridge_83873_9 9 212 0.04245283018867924 chr21 40122854 40122933 chr21_ridge_83870_5 5 79 0.06329113924050633 chr21 40116275 40116854 chr21_ridge_83853_27 27 579 0.046632124352331605 chr21 40116028 40116133 chr21_ridge_83852_5 5 105 0.047619047619047616 chr21 40105512 40106940 chr21_ridge_83824_59 59 1428 0.04131652661064426 chr21 40145359 40145425 chr21_ridge_83941_5 5 66 0.07575757575757576 chr21 44188466 44188549 chr21_ridge_96103_7 7 83 0.08433734939759036 chr21 44190376 44191225 chr21_ridge_96107_36 36 849 0.04240282685512368 chr21 44192551 44192806 chr21_ridge_96112_ll 11 255 0.043137254901960784 chr21 46772280 46772380 chr21_ridge_101794_5 5 100 0.05 chr21 46769732 46770026 chr21_ridge_101789_16 16 294 0.05442176870748299 chr21 46768959 46769170 chr21 ridge 101787 9 9 211 0.04265402843601896 chr21 46767915 46768166 chr21_ridge_101784_17 17 251 0.06772908366533864 chr21 46767026 46767770 chr21_ridge_101783_38 38 744 0.051075268817204304 chr21 46766232 46766593 chr21_ridge_101781_16 16 361 0.0443213296398892 chr21 46765090 46766127 chr21_ridge_101780_59 59 1037 0.05689488910318226 chr21 46764444 46764938 chr21_ridge_101779_26 26 494 0.05263157894736842 chr21 46761653 46761863 chr21 ridge 101775 9 9 210 0.04285714285714286 chr21 46759802 46759983 chr21_ridge_101769_9 9 181 0.049723756906077346 chr21 46759491 46759634 chr21_ridge_101768_6 6 143 0.04195804195804196 chr21 46759001 46759275 chr21_ridge_101767_13 13 274 0.04744525547445255 chr21 46758684 46758896 chr21_ridge_101766_10 10 212 0.04716981132075472 chr21 46758355 46758465 chr21_ridge_101765_5 5 110 0.045454545454545456 chr21 46750780 46751303 chr21_ridge_101748_22 22 523 0.04206500956022945 chr21 46749383 46749770 chr21_ridge_101746_22 22 387 0.056847545219638244 chr21 46747948 46748970 chr21_ridge_101744_51 51 1022 0.049902152641878667 chr21 46741974 46742091 chr21_ridge_101738_5 5 117 0.042735042735042736 chr21 46741596 46741854 chr21_ridge_101737_15 15 258 0.05813953488372093 chr21 46739943 46739985 chr21_ridge_101735_5 5 42 0.11904761904761904 chr21 46736402 46736540 chr21_ridge_101728_6 6 138 0.043478260869565216 chr21 46729044 46729172 chr21_ridge_101703_7 7 128 0.0546875 chr21 46720675 46723534 chr21_ridge_101695_145 145 2859 0.05071703392794683 chr21 46772518 46773134 chr21_ridge_101795_30 30 616 0.048701298701298704 chr21 46774292 46774368 chr21_ridge_101798_5 5 76 0.06578947368421052 chr21 46775299 46775719 chr21 ridge 101802 19 19 420 0.04523809523809524 chr21 46777316 46778628 chr21_ridge_101805_59 59 1312 0.04496951219512195 chr21 46827775 46827893 chr21_ridge_101899_7 7 118 0.059322033898305086 chr21 46824488 46827152 chr21_ridge_101897_264 264 2664 0.0990990990990991 chr21 46822447 46822550 chr21_ridge_101892_5 5 103 0.04854368932038835 chr21 46820965 46821037 chr21_ridge_101886_6 6 72 0.08333333333333333 chr21 46813631 46814067 chr21 ridge 101865 23 23 436 0.052752293577981654 chr21 46812969 46813337 chr21_ridge_101863_28 28 368 0.07608695652173914 chr21 46811975 46812797 chr21_ridge_101862_35 35 822 0.04257907542579075 chr21 46810326 46811592 chr21_ridge_101860_51 51 1266 0.04028436018957346 chr21 46808693 46809133 chr21_ridge_101857_18 18 440 0.04090909090909091 chr21 46803342 46804768 chr21_ridge_101852_62 62 1426 0.043478260869565216 chr21 46801717 46802388 chr21_ridge_101850_29 29 671 0.043219076005961254 chr21 46720002 46720198 chr21_ridge_101693_19 19 196 0.09693877551020408 chr21 46799476 46801583 chr21_ridge_101849_136 136 2107 0.064546748932131 chr21 46796115 46796278 chr21_ridge_101839_8 8 163 0.049079754601226995chr21 46790911 46791286 chr21_ridge_101823_19 19 375 0.050666666666666665 chr21 46790601 46790784 chr21 ridge 101822 14 14 183 0.07650273224043716 chr21 46789560 46789923 chr21_ridge_101818_23 23 363 0.06336088154269973 chr21 46788993 46789338 chr21_ridge_101817_25 25 345 0.07246376811594203 chr21 46787801 46787901 chr21_ridge_101815_6 6 100 0.06 chr21 46787410 46787522 chr21_ridge_101813_6 6 112 0.05357142857142857 chr21 46786900 46787250 chr21_ridge_101812_14 14 350 0.04 chr21 46784184 46786801 chr21_ridge_101811_116 116 2617 0.04432556362246848 chr21 46783640 46784052 chr21_ridge_101810_18 18 412 0 . 043689320388349516 chr21 46782240 46783486 chr21_ridge_101809_53 53 1246 0.04253611556982344 chr21 46798961 46799334 chr21_ridge_101848_19 19 373 0.05093833780160858 chr21 46719486 46719695 chr21_ridge_101691_16 16 209 0.07655502392344497 chr21 46717475 46717619 chr21_ridge_101684_8 8 144 0.05555555555555555 chr21 46714204 46716368 chr21_ridge_101679_89 89 2164 0.0411275415896488 chr21 46644304 46644902 chr21_ridge_101529_25 25 598 0.04180602006688963 chr21 46643558 46643976 chr21_ridge_101527_24 24 418 0.05741626794258373 chr21 46643215 46643411 chr21_ridge_101526_15 15 196 0.07653061224489796 chr21 46640517 46641232 chr21_ridge_101522_35 35 715 0.04895104895104895 chr21 46633930 46633977 chr21_ridge_101497_5 5 47 0.10638297872340426 chr21 46631652 46631871 chr21_ridge_101490_10 10 219 0.045662100456621 chr21 46630440 46630786 chr21_ridge_101487_14 14 346 0 . 04046242774566474 chr21 46630228 46630307 chr21_ridge_101486_5 5 79 0.06329113924050633 chr21 46629922 46630041 chr21_ridge_101485_8 8 119 0.06722689075630252 chr21 46628112 46628264 chr21_ridge_101478_7 7 152 0.046052631578947366 chr21 46627603 46627686 chr21 ridge 101476 6 6 83 0.07228915662650602 chr21 46645114 46645227 chr21_ridge_101530_6 6 113 0.05309734513274336 chr21 46623948 46624102 chr21_ridge_101466_7 7 154 0 . 045454545454545456 chr21 46604859 46605015 chr21_ridge_101417_10 10 156 0.0641025641025641 chr21 46601274 46601305 chr21_ridge_101407_5 5 31 0.16129032258064516 chr21 46599543 46600020 chr21_ridge_101403_20 20 477 0 . 041928721174004195 chr21 46598754 46599124 chr21 ridge 101402 15 15 370 0.04054054054054054 chr21 46598037 46598149 chr21_ridge_101399_5 5 112 0 . 044642857142857144 chr21 46596040 46596609 chr21_ridge_101395_24 24 569 0.0421792618629174 chr21 46594343 46594574 chr21_ridge_101390_10 10 231 0.04329004329004329 chr21 46592671 46592726 chr21_ridge_101385_6 6 55 0.10909090909090909 chr21 46591281 46591316 chr21_ridge_101382_5 5 35 0.14285714285714285 chr21 46591034 46591146 chr21_ridge_101381_5 5 112 0 . 044642857142857144 chr21 46588478 46588601 chr21_ridge_101371_5 5 123 0 . 04065040650406504 chr21 46622448 46623070 chr21_ridge_101460_29 29 622 0.04662379421221865 chr21 46829463 46831147 chr21_ridge_101904_70 70 1684 0.04156769596199525 chr21 46647023 46647182 chr21_ridge_101536_7 7 159 0.0440251572327044 chr21 46650798 46651515 chr21_ridge_101549_36 36 717 0.0502092050209205 chr21 46710039 46710321 chr21_ridge_101675_14 14 282 0.04964539007092199 chr21 46706396 46708793 chr21_ridge_101670_189 189 2397 0.07884856070087609 chr21 46702822 46703497 chr21_ridge_101667_35 35 675 0.05185185185185185 chr21 46702446 46702699 chr21_ridge_101666_ll 11 253 0 . 043478260869565216 chr21 46701349 46702334 chr21_ridge_101665_40 40 985 0.04060913705583756 chr21 46700932 46701096 chr21 ridge 101663 7 7 164 0.042682926829268296 chr21 46696971 46700754 chr21_ridge_101662_161 161 3783 0.042558815754692045 chr21 46696544 46696834 chr21_ridge_101661_20 20 290 0.06896551724137931 chr21 46695839 46696108 chr21_ridge_101659_12 12 269 0.04460966542750929 chr21 46691161 46691263 chr21_ridge_101643_5 5 102 0 . 049019607843137254 chr21 46687860 46689303 chr21_ridge_101638_100 100 1443 0.0693000693000693 chr21 46649613 46650037 chr21 ridge 101544 19 19 424 0.04481132075471698 chr21 46687369 46687731 chr21_ridge_101637_19 19 362 0 . 052486187845303865 chr21 46681937 46682050 chr21_ridge_101630_6 6 113 0.05309734513274336 chr21 46681202 46681294 chr21_ridge_101627_8 8 92 0.08695652173913043 chr21 46679428 46679738 chr21_ridge_101621_13 13 310 0 . 041935483870967745 chr21 46675002 46678282 chr21_ridge_101619_134 134 3280 0.04085365853658537 chr21 46674266 46674719 chr21_ridge_101618_22 22 453 0.04856512141280353 chr21 46673652 46674128 chr21_ridge_101617_23 23 476 0.04831932773109244 chr21 46673340 46673531 chr21_ridge_101616_9 9 191 0 . 04712041884816754 chr21 46673027 46673192 chr21_ridge_101615_7 7 165 0 . 04242424242424243Chr21 46669214 46669289 chr21_ridge_101606_7 7 75 0.09333333333333334 chr21 46662972 46663140 chr21 ridge 101587 8 8 168 0 . 047619047619047616 chr21 46654020 46654555 chr21_ridge_101561_39 39 535 0.07289719626168224 chr21 46684238 46687249 chr21_ridge_101636_143 143 3011 0.04749252739953504 chr21 46831273 46832436 chr21_ridge_101905_49 49 1163 0.04213241616509028 chr21 46835378 46836551 chr21_ridge_101909_55 55 1173 0.04688832054560955 chr21 46836725 46836875 chr21_ridge_101910_7 7 150 0.04666666666666667 chr21 46993692 46994499 chr21_ridge_102156_36 36 807 0.04460966542750929 chr21 46992453 46992586 chr21_ridge_102153_7 7 133 0.05263157894736842 chr21 46992209 46992333 chr21_ridge_102152_5 5 124 0.04032258064516129 chr21 46991225 46991824 chr21_ridge_102149_31 31 599 0.05175292153589316 chr21 46982211 46982267 chr21_ridge_102124_5 5 56 0.08928571428571429 chr21 46979516 46979680 chr21_ridge_102119_ll 11 164 0.06707317073170732 chr21 46979186 46979375 chr21_ridge_102118_ll 11 189 0.0582010582010582 chr21 46975253 46976340 chr21_ridge_102114_89 89 1087 0.08187672493100276 chr21 46974390 46975092 chr21_ridge_102113_54 54 702 0.07692307692307693 chr21 46973456 46973609 chr21_ridge_102110_8 8 153 0.05228758169934641 chr21 46972329 46973319 chr21_ridge_102109_47 47 990 0 . 047474747474747475 chr21 46997272 46997545 chr21_ridge_102160_ll 11 273 0 . 040293040293040296 chr21 46971781 46972120 chr21_ridge_102108_18 18 339 0.05309734513274336 chr21 46970266 46970406 chr21_ridge_102103_6 6 140 0.04285714285714286 chr21 46968312 46968423 chr21_ridge_102096_5 5 111 0 . 04504504504504504 chr21 46966718 46966857 chr21_ridge_102090_7 7 139 0.050359712230215826 chr21 46966087 46966238 chr21_ridge_102087_8 8 151 0.052980132450331126 chr21 46961022 46964915 chr21 ridge 102085 232 232 3893 0.059594143334189574 chr21 46959646 46959964 chr21_ridge_102083_13 13 318 0 . 040880503144654086 chr21 46957037 46958152 chr21_ridge_102081_65 65 1115 0.05829596412556054 chr21 46949846 46952568 chr21_ridge_102075_168 168 2722 0.06171932402645114 chr21 46949514 46949636 chr21_ridge_102074_6 6 122 0.04918032786885246 chr21 46933356 46933558 chr21_ridge_102046_12 12 202 0.0594059405940594 chr21 46932033 46932438 chr21 ridge 102043 31 31 405 0.07654320987654321 chr21 46970513 46970683 chr21_ridge_102104_10 10 170 0 . 058823529411764705 chr21 46931329 46931875 chr21_ridge_102042_24 24 546 0.04395604395604396 chr21 47000290 47000349 chr21_ridge_102163_6 6 59 0.1016949152542373 chr21 47001286 47001548 chr21_ridge_102165_13 13 262 0.04961832061068702 chr21 47054744 47054882 chr21_ridge_102293_9 9 138 0.06521739130434782 chr21 47052937 47054591 chr21_ridge_102292_162 162 1654 0.09794437726723096 chr21 47051765 47051846 chr21_ridge_102289_5 5 81 0.06172839506172839 chr21 47051509 47051646 chr21_ridge_102288_6 6 137 0 . 043795620437956206 chr21 47050812 47051406 chr21_ridge_102287_27 27 594 0 . 045454545454545456 chr21 47049351 47050148 chr21_ridge_102285_32 32 797 0.04015056461731493 chr21 47043445 47043589 chr21_ridge_102266_7 7 144 0.04861111111111111 chr21 47040633 47040788 chr21_ridge_102259_7 7 155 0.04516129032258064 chr21 47038282 47038531 chr21_ridge_102251_13 13 249 0.05220883534136546 chr21 47038010 47038127 chr21_ridge_102250_5 5 117 0 . 042735042735042736 chr21 47035131 47037158 chr21_ridge_102248_85 85 2027 0.04193389245189936 chr21 47000495 47001158 chr21_ridge_102164_34 34 663 0.05128205128205128 chr21 47031417 47031575 chr21 ridge 102243 9 9 158 0.056962025316455694 chr21 47027653 47027738 chr21_ridge_102232_6 6 85 0.07058823529411765 chr21 47026017 47027417 chr21_ridge_102231_80 80 1400 0.05714285714285714 chr21 47025075 47025311 chr21_ridge_102229_10 10 236 0.0423728813559322 chr21 47024687 47024819 chr21_ridge_102227_6 6 132 0 . 045454545454545456 chr21 47021741 47021841 chr21_ridge_102218_5 5 100 0.05 chr21 47018924 47019415 chr21 ridge 102210 21 21 491 0.04276985743380855 chr21 47018674 47018781 chr21_ridge_102209_7 7 107 0.06542056074766354 chr21 47016036 47016413 chr21_ridge_102207_17 17 377 0.04509283819628647 chr21 47012611 47012819 chr21_ridge_102199_ll 11 208 0 . 052884615384615384 chr21 47009383 47011162 chr21_ridge_102195_144 144 1779 0.08094435075885328 chr21 47001693 47001977 chr21_ridge_102166_15 15 284 0.0528169014084507 chr21 47027840 47028088 chr21_ridge_102233_21 21 248 0.0846774193548387 chr21 46587956 46588068 chr21_ridge_101369_5 5 112 0 . 044642857142857144 chr21 46931008 46931225 chr21_ridge_102041_12 12 217 0.055299539170506916 chr21 46926453 46926570 chr21_ridge_102035_9 9 117 0.07692307692307693Chr21 46872215 46872427 chr21_ridge_101960_13 13 212 0.06132075471698113 chr21 46866045 46866240 chr21 ridge 101952 10 10 195 0.05128205128205128 chr21 46864840 46865180 chr21_ridge_101949_17 17 340 0.05 chr21 46863325 46864684 chr21_ridge_101948_64 64 1359 0.047093451066961 chr21 46862373 46863164 chr21_ridge_101947_46 46 791 0.05815423514538559 chr21 46861962 46862264 chr21_ridge_101946_13 13 302 0.04304635761589404 chr21 46861382 46861840 chr21_ridge_101945_22 22 458 0 . 048034934497816595 chr21 46860848 46861252 chr21_ridge_101944_17 17 404 0.04207920792079208 chr21 46858340 46860720 chr21_ridge_101943_139 139 2380 0.058403361344537816 chr21 46856419 46856520 chr21_ridge_101940_6 6 101 0.0594059405940594 chr21 46856239 46856311 chr21_ridge_101939_6 6 72 0.08333333333333333 chr21 46873320 46873487 chr21_ridge_101965_9 9 167 0.05389221556886228 chr21 46854109 46854239 chr21_ridge_101934_7 7 130 0.05384615384615385 chr21 46849707 46851987 chr21_ridge_101927_102 102 2280 0.04473684210526316 chr21 46849240 46849426 chr21_ridge_101925_9 9 186 0.04838709677419355 chr21 46847365 46849115 chr21_ridge_101924_87 87 1750 0.04971428571428571 chr21 46846785 46847158 chr21_ridge_101923_16 16 373 0.04289544235924933 chr21 46845710 46846642 chr21_ridge_101922_43 43 932 0 . 046137339055793994 chr21 46844264 46845591 chr21_ridge_101921_61 61 1327 0 . 045968349660889224 chr21 46843929 46844140 chr21_ridge_101920_9 9 211 0.04265402843601896 chr21 46842954 46843028 chr21_ridge_101918_5 5 74 0.06756756756756757 chr21 46842403 46842627 chr21_ridge_101916_18 18 224 0.08035714285714286 chr21 46839711 46839858 chr21_ridge_101913_7 7 147 0 . 047619047619047616 chr21 46837587 46839569 chr21_ridge_101912_93 93 1982 0.046922300706357216 chr21 46853295 46853483 chr21 ridge 101931 8 8 188 0.0425531914893617 chr21 46928808 46930797 chr21_ridge_102040_112 112 1989 0.0563097033685269 chr21 46874890 46879714 chr21_ridge_101968_204 204 4824 0.04228855721393035 chr21 46884033 46884149 chr21_ridge_101979_5 5 116 0.04310344827586207 chr21 46926105 46926346 chr21_ridge_102034_15 15 241 0 . 06224066390041494 chr21 46924853 46925997 chr21_ridge_102033_64 64 1144 0 . 055944055944055944 chr21 46923769 46924738 chr21 ridge 102032 48 48 969 0.04953560371517028 chr21 46922731 46922946 chr21_ridge_102028_9 9 215 0.04186046511627907 chr21 46918187 46918707 chr21_ridge_102022_34 34 520 0.06538461538461539 chr21 46916156 46916285 chr21_ridge_102017_10 10 129 0.07751937984496124 chr21 46914146 46915366 chr21_ridge_102014_56 56 1220 0.04590163934426229 chr21 46913235 46913766 chr21_ridge_102012_25 25 531 0 . 047080979284369114 chr21 46912041 46913129 chr21_ridge_102011_59 59 1088 0.05422794117647059 chr21 46910093 46911735 chr21_ridge_102009_68 68 1642 0.04141291108404385 chr21 46905767 46907689 chr21_ridge_102007_84 84 1922 0 . 043704474505723206 chr21 46879820 46880462 chr21_ridge_101969_27 27 642 0.04205607476635514 chr21 46900059 46903711 chr21_ridge_102000_150 150 3652 0. 04107338444687842 chr21 46898541 46899401 chr21_ridge_101998_49 49 860 0 . 056976744186046514 chr21 46897499 46898358 chr21_ridge_101997_48 48 859 0.05587892898719441 chr21 46897109 46897392 chr21_ridge_101996_15 15 283 0.053003533568904596 chr21 46894457 46896603 chr21_ridge_101993_133 133 2146 0.0619757688723206 chr21 46891365 46894015 chr21_ridge_101991_116 116 2650 0.04377358490566038 chr21 46890847 46891114 chr21_ridge_101990_25 25 267 0.09363295880149813 chr21 46889789 46890084 chr21 ridge 101987 16 16 295 0.05423728813559322 chr21 46887887 46889442 chr21_ridge_101985_75 75 1555 0.04823151125401929 chr21 46886899 46887751 chr21_ridge_101984_38 38 852 0.04460093896713615 chr21 46886345 46886798 chr21_ridge_101983_21 21 453 0 . 046357615894039736 chr21 46884983 46886173 chr21_ridge_101982_48 48 1190 0 . 040336134453781515 chr21 46899530 46899946 chr21_ridge_101999_22 22 416 0.052884615384615384 chr21 47056797 47058063 chr21 ridge 102304 65 65 1266 0.05134281200631911 chr21 46586993 46587114 chr21_ridge_101365_5 5 121 0.04132231404958678 chr21 46584058 46584105 chr21_ridge_101356_5 5 47 0.10638297872340426 chr21 46280748 46281135 chr21_ridge_100679_18 18 387 0 . 046511627906976744 chr21 46279272 46279435 chr21_ridge_100675_8 8 163 0 . 049079754601226995 chr21 46278874 46279168 chr21_ridge_100674_12 12 294 0.04081632653061224 chr21 46278239 46278698 chr21_ridge_100673_19 19 459 0.04139433551198257 chr21 46276777 46276941 chr21_ridge_100669_10 10 164 0.06097560975609756 chr21 46276068 46276495 chr21_ridge_100667_20 20 427 0.0468384074941452 chr21 46275728 46275961 chr21_ridge_100666_14 14 233 0 . 060085836909871244Chr21 46274661 46275261 chr21_ridge_100664_31 31 600 0.051666666666666666 chr21 46273528 46274539 chr21 ridge 100663 49 49 1011 0.04846686449060336 chr21 46271327 46271520 chr21_ridge_100657_12 12 193 0.06217616580310881 chr21 46270856 46271213 chr21_ridge_100656_17 17 357 0 . 047619047619047616 chr21 46270242 46270755 chr21_ridge_100655_21 21 513 0.04093567251461988 chr21 46268668 46269741 chr21_ridge_100653_54 54 1073 0.05032618825722274 chr21 46268424 46268551 chr21_ridge_100652_8 8 127 0.06299212598425197 chr21 46267227 46267575 chr21_ridge_100650_16 16 348 0.04597701149425287 chr21 46266417 46266591 chr21_ridge_100648_14 14 174 0.08045977011494253 chr21 46265346 46266162 chr21_ridge_100646_37 37 816 0.04534313725490196 chr21 46264987 46265235 chr21_ridge_100645_16 16 248 0.06451612903225806 chr21 46263456 46264863 chr21_ridge_100644_62 62 1407 0 . 04406538734896944 chr21 46263002 46263341 chr21_ridge_100643_14 14 339 0.04129793510324484 chr21 46262815 46262887 chr21_ridge_100642_5 5 72 0 . 06944444444444445 chr21 46260908 46261069 chr21_ridge_100638_7 7 161 0 . 043478260869565216 chr21 46260331 46260470 chr21_ridge_100636_8 8 139 0.05755395683453238 chr21 46281851 46282574 chr21_ridge_100681_30 30 723 0.04149377593360996 chr21 46285169 46285367 chr21_ridge_100686_9 9 198 0 . 045454545454545456 chr21 46288326 46288464 chr21_ridge_100694_6 6 138 0.043478260869565216 chr21 46288923 46289002 chr21_ridge_100697_5 5 79 0.06329113924050633 chr21 46337101 46337202 chr21_ridge_100783_7 7 101 0.06930693069306931 chr21 46336055 46336203 chr21_ridge_100780_8 8 148 0 . 05405405405405406 chr21 46334764 46335479 chr21_ridge_100777_33 33 715 0 . 046153846153846156 chr21 46334320 46334575 chr21_ridge_100776_13 13 255 0.050980392156862744 chr21 46330220 46330726 chr21 ridge 100767 24 24 506 0.04743083003952569 chr21 46329797 46329972 chr21_ridge_100766_9 9 175 0.05142857142857143 chr21 46328531 46329442 chr21_ridge_100764_44 44 911 0 . 048298572996706916 chr21 46327512 46327751 chr21_ridge_100762_ll 11 239 0.04602510460251046 chr21 46326138 46326393 chr21_ridge_100760_ll 11 255 0 . 043137254901960784 chr21 46323123 46324226 chr21_ridge_100757_45 45 1103 0.04079782411604715 chr21 46316800 46320876 chr21_ridge_100755_171 171 4076 0.04195289499509323 chr21 46260141 46260230 chr21_ridge_100635_5 5 89 0 . 056179775280898875 chr21 46315905 46316694 chr21_ridge_100754_33 33 789 0.04182509505703422 chr21 46313317 46313649 chr21_ridge_100749_15 15 332 0 . 045180722891566265 chr21 46311528 46312506 chr21_ridge_100747_42 42 978 0.04294478527607362 chr21 46310196 46310853 chr21_ridge_100743_27 27 657 0.0410958904109589 chr21 46307548 46310087 chr21_ridge_100742_126 126 2539 0.049625836943678614 chr21 46306027 46306937 chr21_ridge_100740_44 44 910 0.04835164835164835 chr21 46303905 46304050 chr21_ridge_100734_6 6 145 0 . 041379310344827586 chr21 46297056 46297317 chr21_ridge_100715_ll 11 261 0.0421455938697318 chr21 46296012 46296206 chr21_ridge_100711_10 10 194 0.05154639175257732 chr21 46292453 46295273 chr21_ridge_100708_261 261 2820 0.0925531914893617 chr21 46291146 46291292 chr21_ridge_100704_6 6 146 0.0410958904109589 chr21 46290175 46290397 chr21_ridge_100701_ll 11 222 0.04954954954954955 chr21 46314611 46314768 chr21_ridge_100752_8 8 157 0 . 050955414012738856 chr21 46259643 46259913 chr21_ridge_100634_17 17 270 0.06296296296296296 chr21 46256647 46258360 chr21_ridge_100631_71 71 1713 0.04144775248102744 chr21 46254085 46255438 chr21 ridge 100626 58 58 1353 0.04286770140428677 chr21 46196581 46196670 chr21_ridge_100474_5 5 89 0.056179775280898875 chr21 46193392 46193841 chr21_ridge_100468_18 18 449 0.0400890868596882 chr21 46191929 46192094 chr21_ridge_100464_9 9 165 0.05454545454545454 chr21 46191234 46191820 chr21_ridge_100463_24 24 586 0 . 040955631399317405 chr21 46187757 46188227 chr21_ridge_100456_21 21 470 0.04468085106382979 chr21 46180278 46180360 chr21 ridge 100443 6 6 82 0.07317073170731707 chr21 46179722 46180158 chr21_ridge_100442_20 20 436 0.045871559633027525 chr21 46176809 46177104 chr21_ridge_100434_13 13 295 0 . 04406779661016949 chr21 46173869 46174402 chr21_ridge_100427_23 23 533 0 . 043151969981238276 chr21 46172772 46173696 chr21_ridge_100426_38 38 924 0.04112554112554113 chr21 46171018 46172501 chr21_ridge_100425_60 60 1483 0.04045853000674309 chr21 46197589 46197717 chr21_ridge_100478_7 7 128 0.0546875 chr21 46169785 46170903 chr21_ridge_100424_58 58 1118 0.0518783542039356 chr21 46155924 46156071 chr21_ridge_100379_6 6 147 0.04081632653061224 chr21 46154492 46155368 chr21_ridge_100377_38 38 876 0.04337899543378995Chr21 46148725 46149023 chr21_ridge_100363_14 14 298 0.04697986577181208 chr21 46143071 46144297 chr21 ridge 100353 72 72 1226 0.05872756933115824 chr21 46141262 46141371 chr21_ridge_100347_6 6 109 0.05504587155963303 chr21 46130034 46132602 chr21_ridge_100322_113 113 2568 0.044003115264797506 chr21 46128490 46129885 chr21_ridge_100321_70 70 1395 0.05017921146953405 chr21 46127823 46128051 chr21_ridge_100319_15 15 228 0.06578947368421052 chr21 46125607 46127707 chr21_ridge_100318_118 118 2100 0.05619047619047619 chr21 46124346 46124843 chr21_ridge_100315_21 21 497 0.04225352112676056 chr21 46120694 46120846 chr21_ridge_100309_7 7 152 0 . 046052631578947366 chr21 46160771 46160852 chr21_ridge_100396_6 6 81 0 . 07407407407407407 chr21 46337376 46337456 chr21_ridge_100784_5 5 80 0.0625 chr21 46205125 46205250 chr21_ridge_100498_7 7 125 0.056 chr21 46209023 46209256 chr21_ridge_100510_12 12 233 0.05150214592274678 chr21 46250685 46250820 chr21_ridge_100620_7 7 135 0.05185185185185185 chr21 46243844 46245451 chr21_ridge_100602_109 109 1607 0.06782825140012445 chr21 46241385 46241462 chr21_ridge_100593_5 5 77 0.06493506493506493 chr21 46241244 46241272 chr21_ridge_100592_6 6 28 0.21428571428571427 chr21 46239738 46240091 chr21_ridge_100588_15 15 353 0 . 042492917847025496 chr21 46239297 46239611 chr21_ridge_100587_18 18 314 0.05732484076433121 chr21 46236725 46239178 chr21_ridge_100586_253 253 2453 0.1031390134529148 chr21 46235287 46235429 chr21_ridge_100581_7 7 142 0.04929577464788732 chr21 46233627 46234165 chr21_ridge_100578_24 24 538 0.04460966542750929 chr21 46232367 46232470 chr21_ridge_100575_5 5 103 0.04854368932038835 chr21 46230399 46230782 chr21_ridge_100570_16 16 383 0.04177545691906005 chr21 46208347 46208498 chr21 ridge 100508 10 10 151 0.06622516556291391 chr21 46228889 46229000 chr21_ridge_100565_9 9 111 0.08108108108108109 chr21 46225369 46225414 chr21_ridge_100555_5 5 45 0.1111111111111111 chr21 46225140 46225251 chr21_ridge_100554_5 5 111 0 . 04504504504504504 chr21 46221215 46222614 chr21_ridge_100547_125 125 1399 0.08934953538241601 chr21 46220836 46221091 chr21_ridge_100546_15 15 255 0.058823529411764705 chr21 46220453 46220637 chr21 ridge 100545 8 8 184 0.043478260869565216 chr21 46220041 46220322 chr21_ridge_100544_12 12 281 0 . 042704626334519574 chr21 46219859 46219877 chr21_ridge_100543_5 5 18 0.2777777777777778 chr21 46219182 46219301 chr21_ridge_100542_5 5 119 0.04201680672268908 chr21 46217351 46217624 chr21_ridge_100536_19 19 273 0.0695970695970696 chr21 46215270 46215407 chr21_ridge_100528_7 7 137 0.051094890510948905 chr21 46214423 46214739 chr21_ridge_100526_13 13 316 0.04113924050632911 chr21 46226754 46227156 chr21_ridge_100561_19 19 402 0.0472636815920398 chr21 46338792 46339259 chr21_ridge_100787_21 21 467 0 . 044967880085653104 chr21 46339859 46340030 chr21_ridge_100789_8 8 171 0.04678362573099415 chr21 46349025 46349130 chr21_ridge_100811_5 5 105 0 . 047619047619047616 chr21 46491742 46493607 chr21_ridge_101082_78 78 1865 0.0418230563002681 chr21 46489260 46489377 chr21_ridge_101075_6 6 117 0.05128205128205128 chr21 46488746 46489098 chr21_ridge_101074_16 16 352 0 . 045454545454545456 chr21 46484333 46484454 chr21_ridge_101060_5 5 121 0.04132231404958678 chr21 46483988 46484107 chr21_ridge_101058_7 7 119 0 . 058823529411764705 chr21 46482781 46482991 chr21_ridge_101056_9 9 210 0.04285714285714286 chr21 46480913 46481060 chr21 ridge 101051 6 6 147 0.04081632653061224 chr21 46476935 46477227 chr21_ridge_101043_12 12 292 0.0410958904109589 chr21 46476246 46476816 chr21_ridge_101042_25 25 570 0 . 043859649122807015 chr21 46474571 46476119 chr21_ridge_101041_72 72 1548 0 . 046511627906976744 chr21 46470787 46471221 chr21_ridge_101033_18 18 434 0 . 041474654377880185 chr21 46493708 46495676 chr21_ridge_101083_269 269 1968 0.1366869918699187 chr21 46468124 46468296 chr21 ridge 101025 7 7 172 0 . 040697674418604654 chr21 46463365 46463700 chr21_ridge_101010_17 17 335 0 . 050746268656716415 chr21 46461993 46462137 chr21_ridge_101007_6 6 144 0 . 041666666666666664 chr21 46460745 46460996 chr21_ridge_101004_15 15 251 0.05976095617529881 chr21 46453274 46454306 chr21_ridge_100987_47 47 1032 0 . 045542635658914726 chr21 46449639 46450321 chr21_ridge_100984_32 32 682 0.0469208211143695 chr21 46447882 46448736 chr21_ridge_100980_51 51 854 0.059718969555035126 chr21 46442799 46442888 chr21_ridge_100969_5 5 89 0 . 056179775280898875 chr21 46442311 46442488 chr21_ridge_100967_8 8 177 0.04519774011299435 chr21 46437674 46442075 chr21_ridge_100966_257 257 4401 0.05839581913201545Chr21 46436841 46436932 chr21_ridge_100963_5 5 91 0 . 054945054945054944 chr21 46436078 46436248 chr21 ridge 100961 8 8 170 0.047058823529411764 chr21 46463819 46463976 chr21_ridge_101011_9 9 157 0.05732484076433121 chr21 46434704 46434844 chr21_ridge_100957_7 7 140 0.05 chr21 46495775 46495974 chr21_ridge_101084_8 8 199 0.04020100502512563 chr21 46497300 46497576 chr21_ridge_101088_18 18 276 0.06521739130434782 chr21 46582860 46582949 chr21_ridge_101352_5 5 89 0.056179775280898875 chr21 46580177 46580250 chr21_ridge_101343_6 6 73 0.0821917808219178 chr21 46573650 46573744 chr21_ridge_101324_5 5 94 0.05319148936170213 chr21 46572179 46572700 chr21_ridge_101321_26 26 521 0 . 04990403071017274 chr21 46568626 46568799 chr21_ridge_101310_7 7 173 0 . 04046242774566474 chr21 46565869 46566140 chr21_ridge_101306_16 16 271 0.05904059040590406 chr21 46562598 46562747 chr21_ridge_101296_6 6 149 0.040268456375838924 chr21 46559346 46559659 chr21_ridge_101287_16 16 313 0.051118210862619806 chr21 46553605 46554507 chr21_ridge_101275_86 86 902 0.09534368070953436 chr21 46551428 46551899 chr21_ridge_101270_19 19 471 0 . 040339702760084924 chr21 46549399 46549706 chr21_ridge_101264_16 16 307 0.05211726384364821 chr21 46496091 46496233 chr21_ridge_101085_8 8 142 0 . 056338028169014086 chr21 46548959 46549204 chr21_ridge_101263_10 10 245 0.04081632653061224 chr21 46547401 46547617 chr21_ridge_101258_10 10 216 0 . 046296296296296294 chr21 46547033 46547172 chr21_ridge_101257_6 6 139 0.04316546762589928 chr21 46544758 46544870 chr21_ridge_101247_5 5 112 0 . 044642857142857144 chr21 46540976 46541084 chr21_ridge_101235_6 6 108 0.05555555555555555 chr21 46529010 46529315 chr21_ridge_101196_36 36 305 0.1180327868852459 chr21 46523895 46524049 chr21 ridge 101175 7 7 154 0 . 045454545454545456 chr21 46521950 46522058 chr21_ridge_101168_5 5 108 0 . 046296296296296294 chr21 46520565 46521601 chr21_ridge_101166_74 74 1036 0.07142857142857142 chr21 46519253 46519350 chr21_ridge_101160_7 7 97 0 . 07216494845360824 chr21 46515413 46515732 chr21_ridge_101152_13 13 319 0.04075235109717868 chr21 46506404 46506761 chr21_ridge_101124_15 15 357 0.04201680672268908 chr21 46548295 46548436 chr21 ridge 101260 6 6 141 0.0425531914893617 chr21 46586202 46586321 chr21_ridge_101362_5 5 119 0.04201680672268908 chr21 46434392 46434604 chr21_ridge_100956_12 12 212 0.05660377358490566 chr21 46430867 46431070 chr21_ridge_100951_12 12 203 0 . 059113300492610835 chr21 46376293 46379089 chr21_ridge_100865_118 118 2796 0.04220314735336195 chr21 46374957 46375389 chr21_ridge_100863_18 18 432 0 . 041666666666666664 chr21 46374121 46374709 chr21_ridge_100861_29 29 588 0.04931972789115646 chr21 46373628 46373973 chr21_ridge_100860_15 15 345 0 . 043478260869565216 chr21 46373019 46373490 chr21_ridge_100859_25 25 471 0.05307855626326964 chr21 46372122 46372239 chr21_ridge_100857_8 8 117 0.06837606837606838 chr21 46371512 46371972 chr21_ridge_100856_28 28 460 0.06086956521739131 chr21 46371319 46371407 chr21_ridge_100855_8 8 88 0.09090909090909091 chr21 46370721 46371217 chr21_ridge_100854_21 21 496 0.04233870967741935 chr21 46370209 46370597 chr21_ridge_100853_20 20 388 0.05154639175257732 chr21 46368791 46370011 chr21_ridge_100852_49 49 1220 0.04016393442622951 chr21 46383041 46383313 chr21_ridge_100874_15 15 272 0.05514705882352941 chr21 46367067 46368666 chr21_ridge_100851_77 77 1599 0.04815509693558474 chr21 46365663 46365963 chr21 ridge 100848 14 14 300 0.04666666666666667 chr21 46365444 46365559 chr21_ridge_100847_8 8 115 0.06956521739130435 chr21 46359340 46360838 chr21_ridge_100834_136 136 1498 0.09078771695594126 chr21 46358975 46359234 chr21_ridge_1...

Claims

WHAT IS CLAIMED IS:

1. A method comprising: obtaining, from a cohort of subjects, a first plurality of samples from healthy subjects and a second plurality of samples from subjects with a phenotype; generating a first set of sequencing data for the first plurality of samples and a second set of sequencing data for the second plurality of samples; constructing, using the first set of sequencing data, the second set of sequencing data, or a combination thereof, one or more sequencing files; preliminarily segmenting data in the one or more sequencing files and obtaining one or more sets of preliminary DNA segments; and generating, for subsequent use in developing one or more tools for detecting the phenotype in a subject, a set of candidate methylation biomarkers for the phenotype, the generating the set of candidate methylation biomarkers comprising applying a model to the one or more sets of preliminary DNA segments.

2. The method of claim 1 , wherein generating the first and second sets of sequencing data comprises performing methylation sequencing of DNA in the first and second pluralities of samples, respectively.

3. The method of claim 1, wherein the first plurality of samples are cell-free DNA (cfDNA) samples and the second plurality of samples are tissue samples.

4. The method of claim 1, wherein the one or more files are generated based on one or more Binary Alignment Map (BAM) files and / or Sequence Alignment Map (SAM) files.

5. The method of claim 1, wherein constructing the one or more sequencing files comprises generating one or more files in which each line corresponds to a DNA fragment.

6. The method of claim 5, wherein, for each DNA fragment, the one or more files identify a chromosome and start and end coordinates.

7. The method of claim 5, wherein for each DNA fragment, the one or more files identify a methylation pattern.

8. The method of claim 5, wherein for each DNA fragment, the one or more files identify a methylation score.

9. The method of claim 5, wherein for each DNA fragment, the one or more files identify at least one coordinate corresponding to one or more methylation sites.

10. The method of claim 1, wherein preliminarily segmenting the data in the one or more sequencing files comprises constructing a set of preliminary segments based at least on a reference methylome.

11. The method of claim 1, wherein preliminarily segmenting the data in the one or more sequencing files comprises constructing a set of preliminary segments based at least on a set of individual methylomes from one or more samples from the cohort of subjects.

12. The method of claim 1, wherein preliminarily segmenting the data in the one or more sequencing files is based on one or more criteria.

13. The method of claim 12, wherein the one or more criteria comprises a primer length threshold for primer length.

14. The method of claim 13, wherein the primer length threshold is between 75 bp and 150 bp.

15. The method of claim 12, wherein the one or more criteria comprises a probe length threshold for probe length.

16. The method of claim 15, wherein the probe length threshold is between 75 bp and 150 bp.

17. The method of claim 12, wherein the one or more criteria comprises a fragment length threshold based on expected fragment lengths.

18. The method of claim 17, wherein the fragment length threshold is between 60 bp and 140 bp.

19. The method of claim 12, wherein the one or more criteria comprises a processivity threshold for the DNA (cytosine-5)-methyltransferase 1 (DNMT1) enzyme.

20. The method of claim 19, wherein the processivity threshold is at least between 20 bp and 1000 bp.

21. The method of claim 12, wherein the one or more criteria comprises a maximum allowable distance between adjacent CpG loci.

22. The method of claim 21, wherein the maximum allowable distance is 150 bp.

23. The method of claim 1, wherein preliminarily segmenting the data comprises removing one or more CpGs that are found in less than a threshold percentage of total samples.

24. The method of claim 23, wherein the threshold percentage is between about 15% and about 35%.

25. The method of claim 1, wherein preliminarily segmenting the data comprises filtering ridges to contain at least a threshold number of CpG sites.

26. The method of claim 25, wherein the threshold number is at least 3 CpG sites.

27. The method of claim 1, wherein preliminarily segmenting the data comprises filtering ridges to have a CpG density of at least a density threshold.

28. The method of claim 27, wherein the density threshold is at least 0.02 CpG / bp.

29. The method of claim 1, wherein preliminarily segmenting the data comprises filtering ridges (i) to autosomes only, (ii) to having at least 5 CpG sites, and (iii) to having a density of at least 0.03 CpG / bp.

30. The method of claim 1, wherein generating the set of candidate methylation biomarkers for the phenotype comprises further segmenting the data.

31. The method of claim 1, wherein the model is a Bayesian model.

32. The method of claim 1, wherein the model is used to infer and / or estimate change points, which indicate boundaries of regions where a methylation load signal has a variation below a threshold in a given region across all samples within the cohort.

33. The method of claim 1, wherein the model fits a piecewise constant function to beta- binomially distributed methylation load signals.

34. The method of claim 1, wherein the model employs stochastic variational inference (SV1).

35. The method of claim 1, further comprising generating a select set of methylation biomarkers from the set of candidate methylation biomarkers.

36. The method of claim 35, wherein generating the select set of methylation biomarkers comprises scoring the methylation biomarkers in the set of candidate methylation biomarkers.

37. The method of claim 36, wherein candidate biomarkers are scored based on a signal-to- noise ratio (SNR) so as to prioritize regions where background noise is minimal compared to phenotype signal.

38. The method of claim 35, wherein generating the select set of methylation biomarkers comprises prioritizing candidate methylation biomarkers based on one or more criteria.

39. The method of claim 38, wherein the one or more criteria comprises designability of probes for the biomarkers.

40. The method of claim 38, wherein methylation biomarkers in repeat or low-complexity regions are deprioritized.

41. The method of claim 38, further comprising prioritizing the methylation biomarkers for predictive powers across subpopulations.

42. The method of claim 35, wherein the select set of methylation biomarkers is a first select set, and wherein the method further comprises generating a second select set of methylation biomarkers.

43. The method of claim 42, wherein the first select set of methylation biomarkers corresponds to a first disease subtype and the second select set of methylation biomarkers corresponds to a second disease subtype.

44. The method of claim 42, wherein the first select set of methylation biomarkers corresponds to a first population and the second select set of methylation biomarkers corresponds to a second population.

45. The method of claim 42, wherein the first select set of methylation biomarkers corresponds to a first gender and the second select set of methylation biomarkers corresponds to a second gender.

46. The method of claim 42, wherein the first select set of methylation biomarkers corresponds to a first ethnicity and the second select set of methylation biomarkers corresponds to a second ethnicity.

47. The method of claim 42, wherein the first select set of methylation biomarkers corresponds to a first disease subtype and the second select set of methylation biomarkers corresponds to a second disease subtype.

48. The method of claim 1, further comprising developing, for detection of the phenotype in a subject, a panel based on the set of candidate methylation biomarkers.

49. The method of claim 48, wherein the set of candidate methylation biomarkers is based on ridges listed in Table P02, DMRs listed in Table P05, biomarkers listed in Table P04, or a combination thereof.

50. The method of claim 48, wherein the set of candidate methylation biomarkers includes 1 or more, 2 or more, 5 or more, 10 or more, 20 or more, 50 or more, 100 or more, or 200 or more biomarkers listed in Table P04.

51. The method of claim 1, further comprising developing, for detection of the phenotype in a subject, a panel based on ridges listed in Table P02, DMRs listed in Table P05, biomarkers listed in Table P04, or a combination thereof.

52. A method comprising: obtaining a first plurality of samples from healthy subjects and a second plurality of samples from subjects with a phenotype; generating methylation sequencing data for the first plurality of samples and the second plurality of samples; constructing, based on the generated methylation sequencing data, one or more sequencing files; preliminarily segmenting data in the one or more sequencing files and obtaining a set of preliminary DNA segments; further segmenting the set of preliminary DNA segments and generating candidate methylation biomarkers; and generating, for subsequent use in developing one or more tools for detecting the phenotype in a subject, a select set of methylation biomarkers from the candidate methylation biomarkers.

53. A method comprising:generating a first set of methylation sequencing data for a first plurality of samples from healthy subjects and a second set of methylation sequencing data for a second plurality of samples from subjects with a phenotype; constructing, using the first set of methylation sequencing data, the second set of methylation sequencing data, or a combination thereof, one or more sequencing files; preliminarily segmenting data in the one or more sequencing files and obtaining one or more sets of preliminary DNA segments; generating a set of candidate biomarkers for the phenotype, the generating the set of candidate biomarkers comprising applying a model to the one or more sets of preliminary DNA segments; and generating a select set of biomarkers from the set of candidate biomarkers for subsequent detection of the phenotype in one or more subjects.

54. A method comprising: receiving methylation sequencing data corresponding to samples from healthy subjects and subjects with a phenotype; constructing, based at least one the methylation sequencing data, one or more sequencing files; preliminarily segmenting data in the one or more sequencing files and obtaining one or more sets of preliminary DNA segments; and generating a set of candidate biomarkers for the phenotype, the generating the set of candidate biomarkers comprising applying a model to the one or more sets of preliminary DNA segments.

55. A method of detecting a phenotype in a subject using a panel developed based on a select set of methylation biomarkers generated by the method of any of claims 1, 52, 53, or 54.

56. A panel for detecting a phenotype in a subject, the panel being based on a select set of methylation biomarkers generated by the method of any of claims 1, 52, 53, or 54.

57. A method of detecting colorectal cancer in a subject using a panel developed based on a select set of methylation biomarkers generated by the method of any of claims 1, 52, 53, or 54.

58. A panel for detecting colorectal cancer in a subject, the panel being based on a select set of methylation biomarkers generated by the method of any of claims 1, 52, 53, or 54.

59. A method of detecting a phenotype in a subject using a panel developed using ridges listed in Table P02, DMRs listed in Table P05, biomarkers listed in Table P04, or a combination thereof.

60. A panel for detecting a phenotype in a subject, the panel being based on ridges listed in Table P02, DMRs listed in Table P05, biomarkers listed in Table P04, or a combination thereof.

61. A panel for detecting a phenotype in a subject, the panel including 1 or more, 2 or more, 5 or more, 10 or more, 20 or more, 50 or more, 100 or more, or 200 or more biomarkers listed in Table P04.

62. A method of detecting colorectal cancer in a subject using a panel developed using ridges listed in Table P02, DMRs listed in Table P05, biomarkers listed in Table P04, or a combination thereof.

63. A panel for detecting colorectal cancer in a subject, the panel being based on ridges listed in Table P02, DMRs listed in Table P05, biomarkers listed in Table P04, or a combination thereof.

64. A panel for detecting colorectal cancer in a subject, the panel including 1 or more, 2 or more, 5 or more, 10 or more, 20 or more, 50 or more, 100 or more, or 200 or more biomarkers listed in Table P04.

65. A computing system comprising one or more processors configured to perform any of the above methods.

Images