3159results about "Proteomics" patented technology

Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists.

Efficient sequence specific gene silencing is possible through the use of siRNA technology. By selecting particular siRNAs by rationale design, one can maximize the generation of an effective gene silencing reagent, as well as methods for silencing genes.

The present invention relates to a pharmaceutical composition comprising a modified mRNA that is stabilised by sequence modifications and optimised for translation. The pharmaceutical composition according to the invention is particularly well suited for use as an inoculating agent, as well as a therapeutic agent for tissue regeneration. In addition, a process is described for determining sequence modifications that promote stabilisation and translational efficiency of modified mRNA of the invention.

“In silico” nucleic acid recombination methods, related integrated systems utilizing genetic operators and libraries made by in silico shuffling methods are provided.

The invention is based, at least in part, on the development of stabilized binding molecules that consist of or comprise a stabilized scFv and methods for making such stabilized molecules.

The information management system disclosed enables caregivers to make better decisions, faster, using aggregated genetic and phenotypic data. The system enables the integration, validation and analysis of genetic, phenotypic and clinical data from multiple subjects who may be at distributed facilities. A standardized data model stores a range of patient data in standardized data classes that encompass patient profile information, patient symptomatic information, patient treatment information, and patient diagnostic information including genetic information. Data from other systems is converted into the format of the standardized data classes using a data parser, or cartridge, specifically tailored to the source system. Relationships exist between standardized data classes that are based on expert rules and statistical models. The relationships are used both to validate new data, and to predict phenotypic outcomes based on available data. The prediction may relate to a clinical outcome in response to a proposed intervention by a caregiver. The statistical models may be inhaled into the system from electronic publications that define statistical models and methods for training those models, according to a standardized template. Methods are described for selecting, creating and training the statistical models to operate on genetic, phenotypic and clinical data, in particular for underdetermined data sets that are typical of genetic information. The disclosure also describes how security of the data is maintained by means of a robust security architecture, and robust user authentication such as biometric authentication, combined with application-level and data-level access privileges.

Disclosed is a method to achieve digital quantification of DNA (i.e., counting differences between identical sequences) using direct shotgun sequencing followed by mapping to the chromosome of origin and enumeration of fragments per chromosome. The preferred method uses massively parallel sequencing, which can produce tens of millions of short sequence tags in a single run and enabling a sampling that can be statistically evaluated. By counting the number of sequence tags mapped to a predefined window in each chromosome, the over- or under-representation of any chromosome in maternal plasma DNA contributed by an aneuploid fetus can be detected. This method does not require the differentiation of fetal versus maternal DNA. The median count of autosomal values is used as a normalization constant to account for differences in total number of sequence tags is used for comparison between samples and between chromosomes.

The present invention relates to methods, systems and apparatus for capturing, integrating, organizing, navigating and querying large-scale data from high-throughput biological and chemical assay platforms. It provides a highly efficient meta-analysis infrastructure for performing research queries across a large number of studies and experiments from different biological and chemical assays, data types and organisms, as well as systems to build and add to such an infrastructure. According to various embodiments, methods, systems and interfaces for associating experimental data, features and groups of data related by structure and/or function with chemical, medical and/or biological terms in an ontology or taxonomy are provided. According to various embodiments, methods, systems and interfaces for filtering data by data source information are provided, allowing dynamic navigation through large amounts of data to find the most relevant results for a particular query.

Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. The determination of the relative amounts may count sequences of only certain length. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists. Prior to sequencing, the biological sample may be enriched for DNA fragments of a particular sizes.

The present disclosure provides methods for determining the ploidy status of a chromosome in a gestating fetus from genotypic data measured from a mixed sample of DNA comprising DNA from both the mother of the fetus and from the fetus, and optionally from genotypic data from the mother and father. The ploidy state is determined by using a joint distribution model to create a plurality of expected allele distributions for different possible fetal ploidy states given the parental genotypic data, and comparing the expected allelic distributions to the pattern of measured allelic distributions measured in the mixed sample, and choosing the ploidy state whose expected allelic distribution pattern most closely matches the observed allelic distribution pattern. The mixed sample of DNA may be preferentially enriched at a plurality of polymorphic loci in a way that minimizes the allelic bias, for example using massively multiplexed targeted PCR.

Aspects of the present invention include methods and compositions for determining the number of individual polynucleotide molecules originating from the same genomic region of the same original sample that have been sequenced in a particular sequence analysis configuration or process. In these aspects of the invention, a degenerate base region (DBR) is attached to the starting polynucleotide molecules that are subsequently sequenced (e.g., after certain process steps are performed, e.g., amplification and/or enrichment). The number of different DBR sequences present in a sequencing run can be used to determine/estimate the number of different starting polynucleotides that have been sequenced. DBRs can be used to enhance numerous different nucleic acid sequence analysis applications, including allowing higher confidence allele call determinations in genotyping applications.

A new method for genomic analysis, termed “Sequence-Based Karyotyping,” is described. Sequence-Based Karyotyping methods for the detection of genomic abnormalities, for diagnosis of hereditary disease, or for diagnosis of spontaneous genomic mutations are also described.

The present invention provides methods for analyzing a combination of biomarkers to individualize tyrosine kinase inhibitor therapy in patients who have been diagnosed with cancer. In particular, the assay methods of the present invention are useful for predicting, identifying, or monitoring the response of a tumor, tumor cell, or patient to treatment with a tyrosine kinase inhibitor using an algorithm based upon biomarker profiling. The assay methods of the present invention are also useful for predicting whether a patient has a risk of developing toxicity or resistance to treatment with a tyrosine kinase inhibitor. In addition, the assay methods of the present invention are useful for monitoring tyrosine kinase inhibitor therapy in a patient receiving the drug to evaluate whether the patient will develop resistance to the drug. Furthermore, the assay methods of the present invention are useful for optimizing the dose of a tyrosine kinase inhibitor in a patient receiving the drug to achieve therapeutic efficacy and/or reduce toxic side-effects.

The present invention describes changes in bacterial gastrointestinal, cutaneous and nasal microbiota associated various mammalian medical conditions. Described are diagnostic tests that arise from combining phylogenetic information about the families, genus, and species of the microbiome and their relative abundance with the metabolic information contained in the metatranscriptome to determine the presence and absence of a disease or medical condition. Provided are compositions of bacteria, co-cultures of bacteria and a carrier for use in treating the disclosed medical conditions. The described compositions restore or correct disease- or medical condition-related imbalances in the microbiome profile with culture-conditioned formulations in which the transcriptome activity of the administered organisms is optimized. Alternatively, formulations of metabolites that drive changes in the metatranscriptome native to the mammal that treat disease or a medical condition or restore health are taught.

A fractional concentration of clinically-relevant DNA in a mixture of DNA from a biological sample is determined based on amounts of DNA fragments at multiple sizes. For example, the fractional concentration of fetal DNA in maternal plasma or tumor DNA in a patient's plasma can be determined. The size of DNA fragments in a sample is shown to be correlated with a proportion of fetal DNA and a proportion of tumor DNA, respectively. Calibration data points (e.g., as a calibration function) indicate a correspondence between values of a size parameter and the fractional concentration of the clinically-relevant DNA. For a given sample, a first value of a size parameter can be determined from the sizes of DNA fragments in a sample. A comparison of the first value to the calibration data points can provide the estimate of the fractional concentration of the clinically-relevant DNA.

The invention provides methods for simultaneously amplifying multiple nucleic acid regions of interest in one reaction volume as well as methods for selecting a library of primers for use in such amplification methods. The invention also provides library of primers with desirable characteristics, such as minimal formation of amplified primer dimers or other non-target amplicons.

Methods for determining statistical models for predicting disease risks of a population are provided. Two types of data associated with members of the population are collected. The data may include both genetic and non-genetic types of data. A candidate statistical model is selected for calculating the disease risk. The model has a plurality of parameters and is a function of only one of the two types of data. A data weight is determined for each member of the population. Members having like data of the other type have like weights. The parameters of the model are optimized by fitting the collected data to the model taking into account of the weights.

A system and method for determining the genetic data for one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available. Genetic data for the target individual is acquired and amplified using known methods, and poorly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related subjects. In accordance with one embodiment of the invention, incomplete genetic data from an embryonic cell is reconstructed using the more complete genetic data from a larger sample of diploid cells from one or both parents, with or without genetic data from haploid cells from one or both parents, and/or genetic data taken from other related individuals. In accordance with another embodiment of the invention, incomplete genetic data from a fetus is acquired from fetal cells, or cell-free fetal DNA isolated from the mother's blood, and the incomplete genetic data is reconstructed using the more complete genetic data from a larger sample diploid cells from one or both parents, with or without genetic data from haploid cells from one or both parents, and/or genetic data taken from other related individuals. In one embodiment, the genetic data can be reconstructed for the purposes of making phenotypic predictions. In another embodiment, the genetic data can be used to detect for aneuploides and uniparental disomy.

Disclosed herein is a system and method for increasing the fidelity of measured genetic data, for making allele calls, and for determining the state of aneuploidy, in one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available. Genetic material from the target individual is acquired, amplified and the genetic data is measured using known methods. Poorly or incorrectly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related individuals. In accordance with one embodiment of the invention, incomplete genetic data from an embryonic cell are reconstructed at a plurality of loci using the more complete genetic data from a larger sample of diploid cells from one or both parents, with or without haploid genetic data from one or both parents. In another embodiment of the invention, the chromosome copy number can be determined from the measured genetic data of a single or small number of cells, with or without genetic information from one or both parents. In another embodiment of the invention, these determinations are made for the purpose of embryo selection in the context of in-vitro fertilization. In another embodiment of the invention, the genetic data can be reconstructed for the purposes of making phenotypic predictions.

Embodiments for calling variations in a sample polynucleotide sequence compared to a reference polynucleotide sequence are provided. Aspects of the embodiments include executing an application on at least one computer that locates local areas in the reference polynucleotide sequence where a likelihood exists that one or more bases of the sample polynucleotide sequence are changed from corresponding bases in the reference polynucleotide sequence, where the likelihood is determined at least in part based on mapped mated reads of the sample polynucleotide sequence; generating at least one sequence hypothesis for each of the local areas, and optimizing the at least one sequence hypothesis for at least a portion of the local areas to find one or more optimized sequence hypotheses of high probability for the local areas; and analyzing the optimized sequence hypotheses to identify a series of variation calls in the sample polynucleotide sequence.

A system and method for obtaining, storing, processing and utilizing immunologic information of individuals and populations is presented. In exemplary embodiments of the present invention, a biological sample can be taken from one or more individuals and the sample submitted to one or more panels of assays. The results of the assays can be stored and analyzed, and such analysis can include (i) calculating derived quantities which take the results of the assays as inputs, and (ii) submitting the results and the derived quantities to a set of rules, each of which has a defined output state. In exemplary embodiments of the present invention, based upon the output state of the rules, an appropriate recommendation as to one or more immunization or other interventions can be generated and incorporated with provider and patient reminders. In exemplary embodiments of the present invention the results of the assays and the recommendation, as well as additional information specific to the individual can be stored for further analysis. In exemplary embodiments of the present invention the assay panel or panels can be chosen as a function of a defined demographic group or enterprise affinity into which the individual corresponds. In exemplary embodiments a database can be maintained for storing and further processing of all immunologic informatics collected according to the methods of the present invention, and can be further processed or used to optimize the delivery of products and/or services in various commercial, research and governmental contexts.

The present invention relates to methods for evaluating and/or predicting the outcome of a clinical condition, such as cancer, metastasis, AIDS, autism, Alzheimer's, and/or Parkinson's disorder. The methods can also be used to monitor and track changes in a patient's DNA and/or RNA during and following a clinical treatment regime. The methods may also be used to evaluate protein and/or metabolite levels that correlate with such clinical conditions. The methods are also of use to ascertain the probability outcome for a patient's particular prognosis.

In one aspect, a system for implementing a copy number variation analysis method, is disclosed. The system can include a nucleic acid sequencer and a computing device in communications with the nucleic acid sequencer. The nucleic acid sequencer can be configured to interrogate a sample to produce a nucleic acid sequence data file containing a plurality of nucleic acid sequence reads. In various embodiments, the computing device can be a workstation, mainframe computer, personal computer, mobile device, etc.

The computing device can comprise a sequencing mapping engine, a coverage normalization engine, a segmentation engine and a copy number variation identification engine. The sequence mapping engine can be configured to align the plurality of nucleic acid sequence reads to a reference sequence, wherein the aligned nucleic acid sequence reads merge to form a plurality of chromosomal regions. The coverage normalization engine can be configured to divide each chromosomal region into one or more non-overlapping window regions, determine nucleic acid sequence read coverage for each window region and normalize the nucleic acid sequence read coverage determined for each window region to correct for bias. The segmentation engine can be configured to convert the normalized nucleic acid sequence read coverage for each window region to discrete copy number states. The copy number variation identification engine can be configured to identify copy number variation in the chromosomal regions by utilizing the copy number states of each window region.

The present invention relates to methods for the diagnosis, evaluation, and treatment of mood disorders, particularly bipolar disorder. In particular, patient test samples are analyzed for the presence and amount of members of a panel of biallelic markers comprising one or more specific markers for bipolar treatment and one or more non-specific markers for bipolar treatment. A variety of markers are disclosed for assembling a panel of markers for such diagnosis and evaluation. Algorithms for determining proper treatment are disclosed. A diagnostic kit for a panel of said markers is disclosed. In various aspects, the invention provides methods for the early detection and differentiation of mood disorders or bipolar treatment. Methods for screening therapeutic compounds for mood disorders are disclosed. The invention (1) gives methods providing rapid, sensitive and specific assays that can greatly increase the number of patients that can receive beneficial treatment and therapy, thereby reducing the costs associated with incorrect diagnosis, and (2) provides methods for improved therapies.

Methods for estimating genomic copy number and loss of heterozygosity using Hidden Markov Model based estimation are disclosed.

The present invention relates to the provision of vaccines which are specific for a patient's tumor and are potentially useful for immunotherapy of the primary tumor as well as tumor metastases. In one aspect, the present invention relates to a method for providing an individualized cancer vaccine comprising the steps: (a) identifying cancer specific somatic mutations in a tumor specimen of a cancer patient to provide a cancer mutation signature of the patient; and (b) providing a vaccine featuring the cancer mutation signature obtained in step (a). In a further aspect, the present invention relates to vaccines which are obtainable by said method.

The present invention relates to methods for the diagnosis and evaluation of stroke and stroke sub-type. A variety of bio-markers are disclosed for assembling a panel for such diagnosis and evaluation. Methods are disclosed for selecting markers and correlating their combined levels with a clinical outcome of interest. In various aspects: the invention provides methods for early detection and differentiation of stroke subtypes, for determining the prognosis of a patient presenting with stroke symptoms, and identifying a patient at risk for hemorrhagic transformation after thrombolyic therapy. Methods are disclosed that provide rapid, sensitive and specific assays to greatly increase the number of patients that can receive beneficial stroke treatment and therapy, and reduce the costs associated with incorrect stroke diagnosis.

A frequency of somatic mutations in a biological sample (e.g., plasma or serum) of a subject undergoing screening or monitoring for cancer, can be compared with that in the constitutional DNA of the same subject. A parameter can derived from these frequencies and used to determine a classification of a level of cancer. False positives can be filtered out by requiring any variant locus to have at least a specified number of variant sequence reads (tags), thereby providing a more accurate parameter. The relative frequencies for different variant loci can be analyzed to determine a level of heterogeneity of tumors in a patient.

Methods, computer program(s) and database(s) to analyze and make use of gene haplotype information. These include methods, program, and database to find and measure the frequency of haplotypes in the general population; methods, program, and database to find correlation's between an individual's haplotypes or genotypes and a clinical outcome; methods, program, and database to predict an individual's haplotypes from the individual's genotype for a gene; and methods, program, and database to predict an individual's clinical response to a treatment based on the individual's genotype or haplotype.

The present invention relates to methods for the diagnosis and evaluation of cardiovascular illness, particularly stroke, myocardial and other cardiovascular damage damage, hypertension treatment. In particular, patient test samples are analyzed for the presence and amount of members of a panel of markers comprising one or more specific markers for cardiovascular illness or hypertension treatment and one or more non-specific markers for cardiovascular illness or hypertension treatment. A variety of markers are disclosed for assembling a panel of markers for such diagnosis and evaluation. Algorithms for determining proper treatment are disclosed. A diagnostic kit for a panel of said markers is disclosed. In various aspects, the invention provides methods for the early detection and differentiation of cardiovascular illness or hypertension treatment. Invention methods provide rapid, sensitive and specific assays that can greatly increase the number of patients that can receive beneficial treatment and therapy, reduce the costs associated with incorrect diagnosis, and provide important information about the prognosis of the patient.