Method for predicting prostate cancer and its uses

By detecting the expression profile and algorithm analysis of sncRNA in urine, the existing prostate cancer screening methods are solved, providing high sensitivity and specific diagnostic and management methods to support personalized treatment decisions.

CN113614249BActive Publication Date: 2025-08-05MIR SCIENTIFIC LLC
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Patent Information

Application Number
CN202080021149.1
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Priority Date
2020-02-18
Filing Date
2020-03-14
Publication Date
2025-08-05
Estimated Expiration
2040-03-14

AI Technical Summary

Technical Problem

The existing prostate cancer screening methods are highly invasive and inaccurate, resulting in many men being unnecessarily subject to invasive examinations and treatments, and lacking effective prognostic tools, and existing genomic methods are not effective in predicting tumor progression.

Method used

By detecting the aggregation expression profile of small non-coding RNA (sncRNA) in urine, SentinelTMPCa, SentinelTMCS and SentinelTMHG tests were used, combined with algorithm analysis, to distinguish the presence or absence of prostate cancer and its level, and provide non-invasive diagnostic and classification methods.

Benefits of technology

Highly sensitive and specific prostate cancer screening is achieved, unnecessary invasive examinations are reduced, accurate disease management and treatment decision-making basis, and can monitor the progression of swelling and response treatment effects.

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Abstract

The present invention relates to compositions and methods for diagnosing, prognosing, monitoring and treating prostate cancer patients. In particular, the present invention relates to the use of miRNA and snoRNA as expression signatures for identifying clinically significant prostate cancer.
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Description

[0001] Cross - reference to related applications

[0002] This application claims the benefit of U.S. Provisional Application No. 62 / 978,184, filed on February 18, 2020, and U.S. Provisional Application No. 62 / 819,325, filed on March 15, 2019, the entire contents of which are incorporated herein by reference. Technical field

[0003] The present invention relates to compositions and methods for diagnosing, prognosing, monitoring, and treating patients with prostate cancer. In particular, the present invention relates to the use of small non - coding RNAs (sncRNAs) such as miRNAs and snoRNAs as expression signatures for identifying prostate cancer with clinical significance. Background art

[0004] Current prostate cancer screening methods include digital rectal examination (DRE), followed by a prostate - specific antigen (PSA) test. The former is invasive, and the latter requires a blood sample to be drawn from the subject.

[0005] Patients with suspected DRE and / or elevated PSA levels are subjected to systematic 12 - core biopsies or magnetic resonance imaging (MRI) - guided targeted needle biopsies. This standard diagnostic strategy is invasive, imprecise, and associated with high - cost morbidity, most notably bacterial infections.

[0006] The PSA test has significant drawbacks. In addition to indicating prostate cancer, elevated PSA levels can also indicate urinary tract infections or prostatitis (inflammation of the prostate or benign prostatic hyperplasia or BPH). The test overdiagnoses prostate cancer, and many men undergo core needle biopsies unnecessarily. The prostate tissue collected during the biopsy is then examined by a pathologist and assigned a Gleason score to assess the grade of the disease. The Gleason score is the sum of two numbers: (1) a primary grade assigned by the pathologist based on the pathologist's determination of the tumor grade in the most common pathology, and (2) a secondary grade based on the tumor grade determination in the next most prominent pathology. For each area, a score of one to five is assigned based on the degree of invasion where the tumor appears, and these two numbers are added together to provide the final Gleason score. Tumors with cells that look close to normal are assigned a low Gleason score (six or below, reported as Gleason 3+3), while tumors with cells that are significantly different from normal prostate cells are assigned a higher Gleason score (seven or above). Low-grade tumors with a low Gleason score are less likely to be aggressive; while tumors with a high Gleason score are more likely to be aggressive and metastatic. Since its implementation, certain aspects of the Gleason scoring system have been problematic - most notably, tumors with Gleason 3+4 and Gleason 4+3 are both reported as Gleason 7, even though the clinical outcomes of these groups are significantly different. Recently, improvements to the Gleason score, called grade grouping, have been adopted to eliminate this problem (grade group 1 (GG1) includes Gleason 3+3; GG2 - Gleason 3+4; GG3 - Gleason 4+3; GG4 - Gleason 4+4 and GG5 - Gleason 5+4 or higher. This change in the scoring system simplifies the reporting of prostate cancer histopathology and eliminates the ambiguity associated with "Gleason 7" tumors, making the classification results more straightforward.

[0007] Biopsy results are negative for approximately 50 - 70% of patients recommended for core needle biopsy based on an "elevated" PSA (>3 ng / mL), while 14% of men with a PSA < 3 ng / mL have prostate cancer but are not routinely biopsied due to their low PSA levels. The combination of PSA screening and core needle biopsy is both invasive and has poor performance characteristics, leaving doctors and patients without reliable measures to select treatment options. As a result, many men unnecessarily opt for clinical intervention, usually prostatectomy. It also hinders the development of new prognostic tools because the Gleason score "gold standard" itself is not a reliable indicator of prostate tumor progression.

[0008] This problem has been recognized for at least 30 years. It remains a major problem today. During this time, there have been many attempts to develop prognostic markers for invasive disease, including ploidy, nuclear morphology and nuclear matrix structure, microarray-based transcriptome analysis, DNA methylation status, and gene fusion detection, such as TMPRSS2:ETS family fusions. None of these methods have proven significantly better than the Gleason score as an indicator of prostate tumor progression. In addition, they have not adequately determined cancer stage or grade.

[0009] Tests have been developed that aim to distinguish cancer status using mRNA expression profiles. However, each has shown significant drawbacks. First, with few exceptions, these assays use tumor material from radical prostatectomy specimens and thus can at most predict early tumor recurrence. While it may be helpful in making postoperative clinical decisions related to ongoing clinical decisions, they are not helpful in distinguishing prostate cancer grade before surgery. Second, many of these genomic approaches focus on specific pathways related to prostate cancer progression, including androgen receptor (AR)-regulated gene expression, epithelial-stromal interactions, and the cell cycle. These assays assume that all prostate tumors develop along a common pathway. Other commercially available biomarker assays use mRNA expression profiles generated by real-time PCR of a subset of genes.

[0010] To date, there have been few genome-wide transcriptome studies of sncRNAs in prostate cancer. In an Affymetrix v.2 microarray containing 723 human miRNAs cataloged in Sanger miRBase v.10.1 (Wellcome Sanger Institute), using Illumina / Solexa deep sequencing and microarray analysis, one study compared the miRNA and snoRNA profiles in (i) samples of fresh-frozen radical prostatectomy for prostate cancer and (ii) adjacent normal tissue from the same patients. The study provided a valuable dataset for comparing the complement of sncRNAs expressed in prostate cancer and the surrounding benign tissue, but was not useful for the rational design of a set of sncRNAs that are prognostic and / or predictive of tumor progression prior to clinical intervention. It is also flawed as a general screening technique because the technique requires microdissected snap-frozen material, which can only be used after surgery and thus cannot be used for diagnosis.

[0011] Therefore, there is a need for an improved method for predicting, screening, and classifying prostate cancer. The present disclosure relates to a non-invasive (by eliminating or reducing unnecessary core needle biopsies) method for screening for the presence or absence of prostate cancer, which method has high sensitivity and specificity.

[0012] The method also provides a platform for disease management, which can be used for disease diagnosis, classification, prognosis, and monitoring of progression and treatment. The disclosed method is based on the combination of Sentinel TM PCa, Sentinel TM CS, and Sentinel TM HG tests interrogate a large number of at least 200 small non-coding RNAs (sncRNAs) isolated from urinary exosomes. Sentinel TM PCa, Sentinel TM CS, and Sentinel TM HG tests are based on the algorithmic analysis and comparison of snRNA sequences cataloged from a large target population that is for Sentinel TM PCa testing, with no evidence of prostate cancer (NEPC) or having prostate cancer (GG1-GG5); for Sentinel TM CS testing, having low-grade cancer (GG1) compared to intermediate and high-grade cancers (GG2-GG5); and for Sentinel TM HG testing, having low and favorable intermediate-grade cancers (GG1+GG2) compared to unfavorable intermediate and high-grade (GG3-GG5) cancers. Three Sentinel TM tests that can be performed on a single urine sample are used to sequentially determine whether a patient has prostate cancer and whether a prostate cancer patient has low or favorable intermediate-grade disease that can be monitored on an active surveillance protocol or high-grade disease that requires immediate treatment. Summary of the Invention

[0013] In one aspect, the present disclosure provides a method for screening prostate cancer in a subject, comprising: (i) obtaining a biological sample from the subject, (ii) detecting an aggregate expression profile of a set of small non-coding RNA (sncRNA) features from the biological sample, wherein the set of sncRNAs comprises SEQ ID NO: 1-280, (iii) correlating the aggregate expression profile of SEQ ID NO: 1-280 of the subject by comparing the aggregate expression levels of SEQ ID NO: 1-280 in a training dataset from a target population with no evidence of prostate cancer (NEPC) or having prostate cancer; and (iv) classifying the subject as NEPC or having prostate cancer based on the results in (iii). This procedure is embodied in Sentinel TM PCa test.

[0014] In another aspect, the present disclosure provides a method for determining whether a patient diagnosed with cancer has a low-grade (GG1) or intermediate- or high-grade disease (GG2-GG5), comprising: (i) obtaining a biological sample from a subject, (ii) detecting an aggregate expression profile of a set of small non-coding RNA (sncRNA) features from the biological sample, wherein the set of sncRNAs comprises SEQ ID NOs: 281-560, (iii) correlating the aggregate expression profile of SEQ ID NOs: 281-560 of the subject by comparing the aggregate expression profile of SEQ ID NOs: 281-560 in a training dataset of a target population known to have low-risk, low-grade (GG1) or intermediate- and high-grade, intermediate- and high-risk prostate cancer (GG2-GG5); and (iv) classifying the subject as GG1 or GG2-GG5 based on the results obtained in (iii). This process is embodied in Sentinel TM CS test.

[0015] In another aspect, the present disclosure provides a method for determining whether a patient diagnosed with cancer has a high-grade (GG3-GG5) (low or intermediate-grade disease (GG1+GG2)), comprising: (i) obtaining a biological sample from a subject, (ii) detecting an aggregate expression profile of a set of small non-coding RNA (sncRNA) features from the biological sample, wherein the set of sncRNAs comprises SEQ ID NOs: 561-840, (iii) correlating the aggregate expression profile of SEQ ID NOs: 561-840 of the subject by comparing the aggregate expression profile of SEQ ID NOs: 561-840 in a training dataset of a target population known to have high-grade, high-risk prostate cancer (GG3-GG5) or low or intermediate-risk cancer (GG1+GG2); and (iv) classifying the subject as GG3-GG5 or GG1+GG2 based on the results obtained in (iii). This procedure is embodied in Sentinel TM HG test.

[0016] In yet another aspect, the present disclosure provides a method for treating prostate cancer, comprising: (i) obtaining a biological sample from a subject; (ii) detecting an aggregate expression profile of a set of features of small non-coding RNAs (sncRNAs) from the biological sample, wherein the set of sncRNAs comprises SEQ ID NOs: 281-840; (iii) correlating the aggregate expression profile of SEQ ID NOs: 1-840 of the subject by comparing the aggregate expression profile of SEQ ID NOs: 281-840 in a training dataset of a target population having NEPC, GG1, GG2, GG3, GG4 or GG5 prostate cancer; (iv) classifying the subject as having intermediate-low grade prostate cancer (GG1-GG2) or high grade prostate cancer (GG3-GG5) based on the results obtained from (iii); and (v) treating the subject classified as having high-risk prostate cancer by administering one or more chemotherapeutic agents, hormones, immunotherapies, radiation, cryotherapy, surgery or a combination thereof.

[0017] In a further aspect, the present disclosure provides a method for determining the likelihood of survival, disease recurrence or response to treatment of a subject having prostate cancer, comprising: (i) obtaining a biological sample from the patient; (ii) detecting an aggregate expression profile of a set of features of small non-coding RNAs (sncRNAs) from the biological sample, wherein the set of sncRNAs comprises SEQ ID NOs: 1-840; (iii) comparing the aggregate expression profile of SEQ ID NOs: 1-840 after treatment with that before treatment; (iv) correlating the aggregate expression profile of SEQ ID NOs: 1-840 of the subject by comparing the aggregate expression profile of SEQ ID Nos: 1-840 in a training dataset of a target population having no evidence of prostate cancer (NEPC) or having prostate cancer and the aggregate expression profile of SEQ ID Nos: 1-840 in a training dataset of a target population having grade groups 1, 2, 3 or 4-5; and (v) determining the likelihood of survival, disease recurrence or response to treatment of a subject receiving treatment for prostate cancer.

[0018] In one aspect, the present disclosure provides a method for predicting future prostate cancer in a subject, comprising: (i) obtaining a biological sample from a patient, (ii) detecting an aggregate expression profile of a set of features of small non-coding RNAs (sncRNAs) from the biological sample, wherein the set of sncRNAs comprises SEQ ID NOs: 1-280, (iii) correlating the aggregate expression profile of SEQ ID NOs: 1-280 of the subject by comparing the aggregate expression profile of SEQ ID No: 1-280 in a training dataset of a target population having grade groups 1, 2, 3 or 4-5; (iv) determining the likelihood of a subject at risk of having grade 2-5 prostate cancer based on the results obtained from (iii), and (iv) treating a subject predicted to have a high risk of developing aggressive prostate cancer by administering one or more chemotherapeutic agents, hormones, immunotherapies, radiation, cryotherapy, surgery or combinations thereof.

[0019] In another aspect, the present disclosure provides a system for determining whether a patient has cancer or has cancer and classifying a subject having cancer as (i) indolent (low grade, GG1), (ii) medium or high grade (GG2-GG5), (iii) low / medium risk (GG1-GG2) or (iv) aggressive (high grade, GG3-GG5) prostate cancer, the system comprising at least three processors configured to (a) interrogate an information sequence of an sncRNA sequence, (b) determine and compare Sentinel scores to determine whether a subject has prostate cancer or does not have prostate cancer, and classify the prostate cancer staging group. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] This patent or application file contains at least one color drawing. Copies of this patent or patent application publication with one or more color drawings will be provided by the Office upon request and payment of the necessary fee.

[0021] Figure 1 : Exosomes are small extracellular membrane-bound vesicles that form in early endosomes and are released from cells. Exosomes contain proteins, mRNAs, and an array of sncRNAs [miRNAs and C / D box and H / ACA box small nucleolar RNAs (snoRNAs)] that reflect cell biology.

[0022] Figure 2 : Using a commercial kit, cell-free urine was collected from the patient. Exosomes in the urine were captured, and RNA was extracted from the exosomes. RNA yield was measured using Qubit analysis (ThermoFisher), and sample quality was evaluated using an Agilent 2100 Bioanalyzer. Using specifically for miR Scientific Sentinel TMPCa, Sentinel TM CS or Sentinel TM Custom OpenArray for HG test design TM (Thermo Fisher) plates interrogate the resulting sncRNA levels. Interrogation is a general technical term for simultaneously analyzing large numbers of sequences in a biological sample. The resulting readings of the amplification curves of snoRNA and microRNA (collectively sncRNA) are then analyzed and used to diagnose patients, classify the disease when cancer is present, and monitor treatment accordingly.

[0023] Figure 3 Illustrates the complexity of establishing unbiased statistical methods using more than a single entity to identify important interactions to identify individuals and combinations of sncRNA and correlate rank groupings or prostate cancer phenotypes. (See

[00048] -

[00051] ).

[0024] Figure 4 Shows a schematic diagram for screening and diagnosing patients suspected of having prostate cancer.

[0025] Patients first provide a urine sample for triple Sentinel TM analysis. Total urinary exosomal RNA is extracted and the following expressions are interrogated: sncRNA specific for Sentinel TM PCa test (SEQ ID NO: 1-280); sncRNA specific for Sentinel TM CS test (SEQ ID NO: 281-560); and sncRNA specific for Sentinel TM HG test (SEQ ID NO: 561-840). The expression profiles will be used to classify patients as prostate cancer patients and non-prostate cancer patients (Sentinel TM PCa test, layer 1). Patients with negative scores will return for monitoring every 12 months.

[0026] In the second layer, patients with a positive Sentinel TM PCa score (patients with prostate cancer) will undergo a secondary analysis using the Sentinel TM CS test, which will classify them as clinically insignificant (GG1) tumors or clinically significant tumors (GG2-GG5). Patients with clinically insignificant (GG1) tumors will be recommended for active surveillance (AS) and continuous monitoring by quarterly Sentinel TM CS tests to determine that the tumor has not progressed to GG2 or higher. Patients with clinically significant tumors (GG2-GG5) will be referred for immediate treatment.

[0027] For some patients, the third classification layer, Sentinel TM HG test will further classify patients as having GG1-GG2 tumors or GG3-GG5 tumors. This test aims to identify patients with GG3-GG5 cancers who require immediate intervention. GG1 or GG2 patients can be monitored by Sentinel TM HG test quarterly to identify patients who progress to GG3 and thus require treatment intervention. Sentinel TM CS and Sentinel TM The availability of HG provides personalized information for both patients and healthcare providers to make treatment decisions.

[0028] Figure 5 Shows the output of the PCa discovery experiment. The PCa discovery study used a very carefully defined patient cohort [NEPC = 89; cancer (GG1-GG5) = 146] with well-characterized histopathology to identify the most informative sequences among 6,599 sncRNAs interrogated on the miR4.0 microarray.

[0029] Figure 5 (Left inset): Scatter plot of the cancer-free (NEPC) and cancer (GG1-GG5) status in the training dataset. A positive discovery PCa score indicates prostate cancer, while a negative discovery PCa score indicates no cancer. The cancer status determined by the histopathology of the core biopsy is shown as blue (cancer-free) and red (cancer) circles.

[0030] Figure 5 (Right inset): Identification of informative sncRNAs for the Sentinel TM PCa test to identify the most informative sncRNA entities (showing the top 35, each circle represents an entity), for differentiating cancer-free and cancer status using a proprietary selection algorithm. The resulting Sentinel TM PCa test interrogated 280 sncRNAs, including 145 of the most informative sncRNA sequences, which included 60 snoRNA and 85 miRNA entities, as shown in the bar chart. Green: miRNA entities; yellow: snoRNA entities.

[0031] Figure 6(Left inset) shows the output of the Discovery CS experiment. The CS discovery study used a very carefully defined patient cohort [GG1 = 90; GG2 - GG5 = 56] with well - characterized histopathology to identify the most informative sequences among the 6,599 sncRNAs interrogated on the miR4.0 microarray. A positive Discovery CS score indicates patients with GG2 - GG5 cancers (yellow circles), while a negative Discovery CS score indicates patients with GG1 cancers (green circles).

[0032] Figure 6 (Right inset): For Sentinel TM Identification of informative sncRNAs for the Sentinel CS test to identify the most informative sncRNA entities (showing the top 35, each circle represents an entity), for distinguishing GG1 and GG2 - GG5 cancer states using a proprietary selection algorithm. The resulting Sentinel TM The CS test interrogated 280 sncRNAs, including 145 of the most informative sncRNA sequences, which included 66 snoRNAs and 130 miRNA entities, as shown in the bar graph. Green: miRNA entities; Yellow: snoRNA entities.

[0033] Figure 7 (Left inset) shows the output of the Discovery HG experiment. The HG discovery study used a very carefully defined patient cohort [GG1+GG2 = 181; GG3 - GG5 = 55] with well - characterized histopathology to identify the most informative sequences among the 6,599 sncRNAs interrogated on the miR4.0 microarray. A positive Discovery HG score indicates patients with GG3 - GG5 cancers (purple circles), while a negative Discovery HG score indicates patients with GG1+GG2 cancers (brown circles).

[0034] Figure 7 (Right inset): For Sentinel TM Identification of informative sncRNAs for the Sentinel HG test. The most informative sncRNA entities were identified (showing the top 35, each circle represents an entity) using a proprietary selection algorithm for distinguishing GG1 and GG2 - GG5 cancer states. The resulting Sentinel TM The CS test interrogated 280 sncRNAs, including 196 of the most informative sncRNA sequences, which included 66 snoRNAs and 130 miRNA entities, as shown in the bar graph. Green: miRNA entities; Yellow: snoRNA entities.

[0035] Figure 8 A - 8C shows the use of Sentinel TMPCa test for high-throughput OpenArray of urinary exosome sncRNA TM Clinical validation of the interrogation. Data from a case-control study of 1436 men (836 subjects in the training set used for cross-validation of sncRNA interrogations identified in the discovery PCa phase and 600 independent subjects used in the validation study) are shown.

[0036] Figure 8 A: Scatter plot of cancer status in the validation group of 600 patients (300 cancer-free; 300 with cancer). Classification of cancer-free (black circles) and cancer (green circles) patients, where a positive Sentinel TM PCa score indicates prostate cancer, while a negative Sentinel TM PCa score indicates no cancer.

[0037] Figure 8 B: Ordination plot of cancer status in the validation group of 600 patients. Classification of cancer-free (black circles) and cancer (green circles) patients, where a positive Sentinel TM PCa score indicates prostate cancer, while a negative Sentinel TM PCa score indicates no cancer.

[0038] Figure 8 C: Receiver operating curve (ROC) of the Sentinel TM PCa test. Figure 8 The ROC curves of the analysis of the 600 patients in the test group shown in A and 8B were calculated by continuously calculating the (1 - specificity) for different user-defined false negative rates. The performance characteristics reported in Table 6 (see [000112]) are from a user-defined false negative rate of 0.05 (shown in red).

[0039] Figure 9 A - 9C show the clinical validation of the high-throughput OpenArray of urinary exosome sncRNA using the Sentinel TM CS test for the interrogation. TM Clinical validation of the interrogation. Data from a case-control study of 1436 men (836 subjects in the training set used for cross-validation of sncRNA interrogations identified in the discovery CS phase and 600 independent subjects used in the validation study) are shown.

[0040] Figure 9A: Scatter plot examining cancer status in a validation cohort of 300 prostate cancer patients (146 GG1-low grade and 154 GG2-GG5 intermediate and high grade). Classification of patients with low grade (cyan circles) and intermediate and high grade cancer (orange circles) where positive Sentinel TM CS scores indicate high-grade prostate cancer, while negative Sentinel TM The CS score indicates low-grade cancer.

[0041] Figure 9 B: Check 300 prostate cancer patients Figure 9 Rank plot of cancer status in the validation set shown in A. Classification of patients with low-grade (cyan circles) and high-grade cancer (orange circles), where positive Sentinel TM CS scores indicate high-grade prostate cancer, while negative Sentinel TM The CS score indicates low-grade cancer.

[0042] Figure 9 C: Sentinel TM Receiver operating curve (ROC) of CS test. Figure 9 The ROC curves for the analysis of 300 prostate cancer patients shown in A and 9B were calculated by continuously calculating (1-specificity) for different user-defined false negative rates. The performance characteristics reported in Table 6 (see [000112]) are derived from a user-defined false negative rate of 0.05 (shown in red).

[0043] Figure 10 A-10C shown using Sentinel TM HG test for urine exosomal sncRNAs using high-throughput OpenArray TM Clinical Validation of the Interrogation. Data from a case-control study of 1436 men (836 subjects in a training set used to cross-validate the same sncRNA interrogation identified in the discovery HG phase and 600 independent subjects used in the validation study) are shown.

[0044] Figure 10 A: Scatter plot of cancer status in a validation set of 300 prostate cancer patients (200 GG1+GG2 low grade and 100 GG3-GG5 intermediate and high grade). Classification of patients with low grade (cyan circles) and intermediate and high grade cancer (orange circles), where positive Sentinel TM CS scores indicate high-grade prostate cancer, while negative Sentinel TM The CS score indicates low-grade cancer.

[0045] Figure 10 B: Examine the sorting plot of the cancer status in the validation group as shown in Figure 10 A for 300 prostate cancer patients. Classification of patients with low-grade (blue circles) and high-grade cancer (red circles), where a positive Sentinel TM HG score indicates high-grade prostate cancer, while a negative Sentinel TM HG score indicates low-grade cancer.

[0046] Figure 10 C: Receiver operating curve (ROC) of the Sentinel TM HG test. The ROC curves for the analysis of 300 prostate cancer patients as shown in Figure 10 A and 10B were calculated by continuously calculating the different user-defined false negative rates (1 - specificity). The performance characteristics reported in Table 6 (see [000112]) are from the user-defined false negative rate of 0.05 (shown in red). Detailed implementation

[0047] The present subject matter can be more easily understood by referring to the following detailed description that forms a part of the present disclosure. It should be understood that the present invention is not limited to the specific products, methods, conditions or parameters described and / or shown herein, and the terms used are for the purpose of describing specific aspects and embodiments by way of example only and are not intended to limit the claimed invention.

[0048] The present invention relates to a method for screening, diagnosing and treating prostate cancer in a subject. The method provides robust tests to (1) classify male patients with unknown prostate cancer status and (2) accurately distinguish the grades of prostate cancer in biological samples from patients. The method is based on the detection and correlation of the aggregated expression profiles of a set of sncRNAs from a patient's biological sample to determine whether the patient has prostate cancer using the Sentinel TM PCa test. For patients identified as having prostate cancer, exosomal sncRNAs are further interrogated, which uses the Sentinel TM Clinically significant (CS) test to distinguish patients with clinically significant or invasive (GG2 - GG5) from patients with clinically insignificant or indolent (GG1) prostate cancer, and the Sentinel TM High-grade (HG) test to identify patients with high-grade, high-risk (GG3 - GG5) prostate cancer.

[0049] The disclosed method is based on an unbiased statistical method that has been developed to identify important interactions of individual sequences and combinations of sequences that are most relevant to a phenotype of interest. The method is based on (i) the regulatory effect of miRNAs on mRNAs and (ii) the effect of snoRNAs on the translatability of mRNAs through post-transcriptional modification of ribosomal RNAs, tRNAs, and other nuclear RNAs, which results in new protein products that alter protein function and phenotype.

[0050] The disclosed computational / statistical method analyzes urinary exosomal sncRNAs to provide a very fine analysis of the critical associations between sncRNAs, which leads to the identification of Sentinel sequences that accurately predict prostate cancer phenotypes. Att Figure 3 This is illustrated as follows. For example, in a single entity analysis, the expression level of an individual sncRNA is correlated with the grade group (phenotype) of prostate cancer. For each sncRNA entity, there are two informative outcomes: an increase in the expression level of the entity relative to a control pathology (e.g., no cancer) or a decrease in the expression level. No change in expression between the two phenotypes indicates (1) no association with either phenotype and (2) that the entity cannot be used as a marker for either phenotype. Thus, when using a single entity in the analysis, there are only two informative outcomes, such that all possible sncRNA interactions are not explored.

[0051] In a two entity analysis, examining the associations of expression changes of all possible interactions between two entities results in 8 different informative outcomes and 1 non-informative outcome (when neither phenotype of the two entities is differentially expressed) (see Figure 3 “Query of 2 entities”). Thus, in the context of the Sentinel TM test, when comparing all possible combinations of two sncRNA entities with a specific grade group, there are 8 different ways that will result in a meaningful association between the sncRNA pair and the grade group. This provides a more detailed analysis that reveals hidden associations between sncRNA expression levels and grade grouping.

[0052] The same method using three or four or more sncRNA entities allows for a very fine analysis of the associations between sncRNA expression and phenotype (grade grouping), such that patients with unknown disease states can be evaluated and the individual disease state predicted using the algorithm-selected urinary exosomal sncRNA expression levels.

[0053] Sentinel TM PCa and Sentinel TM HG test Sentinel TM Development of the CS platform

[0054] SentinelTM The PCa test is a classification platform or algorithm based on the analysis of a set of levels of the feature sncRNAs (i.e., miRNA and snoRNA sequences). The predicted value for each sequence is defined by a data-driven selection algorithm that is independent of the prior determined biological role of the sequence in prostate biology. The selection algorithm is trained on a dataset consisting of: (1) control subjects with conditions unrelated to prostate cancer presenting at a urology clinic; (2) suspected prostate cancer subjects known to have no prostate cancer based on biopsy results; and (3) patients diagnosed with prostate cancer and having a core needle biopsy histopathology report graded groups 1 to 5 (GG1 - GG5).

[0055] For establishing a robust dataset for the Sentinel TM test, exosomal sncRNAs obtained from urine exosomes of these patient training sets were interrogated using Affymetrix miR 4.0 microarrays to define expression signatures. These studies using selected subjects with well - characterized histopathology are referred to as the discovery PCa, discovery CS, and discovery HG tests. Patients included in the “cancer - free” group were carefully selected from age - matched men presenting at a urology clinic for problems unrelated to urologic oncology and men who had undergone one or more 12 - needle diagnostic core needle biopsies showing no evidence of prostate cancer (NEPC). For patients in the “cancer” cohort, the pathologic grade group classification of the core needle biopsy for each tumor was comprehensively evaluated. These carefully selected patient groups (cancer - free and cancer groups at different cancer stages) constituted the training set in the development of the discovery PCa, CS, and HG tests. Demographics of the 235 patients used for the discovery experiments are shown in Table 4 (see [000103] - [000104])

[0056] Selection algorithm

[0057] The selection algorithm is used to identify the most informative sncRNA sequences that distinguish cancer from non-cancer, which determines which sncRNA sequences differ between patients without prostate cancer (NEPC) and patients with prostate cancer (GG1-GG5). The discovery PCa test is illustrated below. The selection algorithm tests how well the levels of urinary exosomal sncRNAs correlate with disease pathological stage (cancer / non-cancer) in a large group of participants with well-defined pathology [89 NEPC subjects and 146 cancer patients (GG1-GG5)]. The selection algorithm individually evaluates how well each of the 6,599 sncRNAs interrogated on the miR4.0 array correlates with the known tumor pathology. Since many sncRNAs are coordinately regulated, the algorithm then evaluates all combinations of 2 sncRNAs, 3 sncRNAs, or 4 sncRNAs, and then uses a leave-one-out strategy to examine each individual sncRNA to assess the importance of each individual sncRNA in the pathology of the disease. As expected, excluding most of the 6,599 sncRNA sequences from the selection algorithm has no effect on distinguishing patients with prostate cancer from those without, as they are not differentially associated with either pathology. The impact of the sncRNAs evaluated can be visualized using the importance plot shown in Figure 5 (right small figure). The importance plot shows the following: (1) some exosomal sncRNAs are present at different levels in different pathologies, (2) the sncRNAs are snoRNAs and miRNAs, indicating that one type of sncRNA is not sufficient for the disclosed analysis, and (3) there will be no change in more than 280 sncRNA sequences in the classification assessment using the algorithm for diagnosis.

[0058] The informative sequences for the discovery CS test (which distinguishes low-risk (GG1) and medium-high-risk prostate cancer (GG2-GG5)) were determined using appropriate grade groups and the same selection strategy ( Figure 6 ). The patient population used for this analysis included 89 NEPC subjects and 146 cancer patients (GG1-GG5)

[0059] The informative sequences for the discovery HG test (which distinguishes low and medium-risk (GG1+GG2) and high-grade, high-risk (GG3-GG5) prostate cancer) were also determined similarly ( Figure 7 ). The patient population used for this analysis included 181 GG1+GG2 cancer patients and 55 GG3-GG5 cancer patients. ( Figure 7 ).

[0060] It is important to note that although some sncRNAs are common between the tests, their relative importance in disease state classification varies depending on the test (i.e., the discovery PCa test, the CS test, and the HG test).

[0061] For each test, the 280 most informative sncRNAs (SEQ.ID NO: 1 - 840) were used to design a custom OpenArray TM platform. The OpenArray TM platform used for each Sentinel TM test was further validated in a large case - control study of 1436 patients. The demographics of the subjects used for training and validating Sentinel TM PCa, Sentinel TM CS, and Sentinel TM HG tests are shown in Table 5 (see [000109] - [000110]). A stratified random sample of 600 subjects was selected to identify the validation dataset; the remaining 836 subjects served as the training dataset. The validation samples of 600 patients were stratified so that an equal number of subjects were biopsy - negative and biopsy - positive (300 each), and among the biopsy - positive cases, 200 were GG1+GG2 (146 GG1 and 54 GG2) and 100 were GG3 - GG5.

[0062] Sentinel for identifying prostate cancer TM PCa test

[0063] Sentinel TM PCa, Sentinel TM CS, and Sentinel TM HG tests are based on a classification algorithm that takes as input the sncRNA expression profile of each patient with an unknown disease state and produces a Sentinel TM score; participants are classified by comparing this score to a pre - determined cut - off value (obtained from cross - validation in the training dataset) that controls the sensitivity for classifying future patients with an unknown disease state (but known expression profile) at a user - defined level (usually 95% or higher).

[0064] The Sentinel PCa score is compared to a calculated cut - off value that controls the sensitivity of future patients at a desired level, e.g., 95%, to distinguish between patients with and without prostate cancer for the PCa test ( Figure 7 ). Sentinel TMThe PCa test uses 280 sncRNAs (identified by the discovery PCa test), of which 145 unique sncRNAs: 60 miRNAs and 85 snoRNAs are highly informative. This defines the classification boundary for classifying patients as having or not having prostate cancer. The cut-off value is determined by an algorithm such that the Sentinel PCa score correctly classifies patients as having cancer in 19 out of 20 cases (i.e., with 95% sensitivity). TM The PCa score correctly classifies patients as having cancer in 19 out of 20 cases (i.e., with 95% sensitivity).

[0065] Table 1: SEQ ID NO: 1 - 280 for PCa test analysis

[0066]

[0067]

[0068]

[0069]

[0070]

[0071]

[0072]

[0073]

[0074]

[0075]

[0076]

[0077]

[0078]

[0079]

[0080]

[0081]

[0082]

[0083]

[0084]

[0085]

[0086] Sentinel TM CS detection for identifying low-grade (indolent) prostate cancer

[0087] Sentinel TM The Clinical Significance (CS) test uses a similar classification algorithm to generate Sentinel TM CS scores and compares them to a calculated cutoff value. The cutoff value controls the sensitivity of future patients at the desired level (95%) to distinguish clinically significant cancers (GG2-GG5) (if the Sentinel TM CS score is greater than or equal to the cutoff value) and clinically insignificant cancers (GG1)) (if the Sentinel TM CS score is less than the cutoff value). The algorithm is trained using only the subset of patients known to have prostate cancer in the dataset used to train the Sentinel TM PCa test. Similarly, using a classification algorithm, 280 sncRNAs are used as a basis to define the expression signature of the Sentinel TM CS test. The Sentinel TM CS test uses 280 sncRNAs (identified by the discovery CS test, of which 135 unique sncRNAs: 130 miRNAs and 66 snoRNAs are highly informative.

[0088] Table 2: SEQ ID NOs: 281 - 560 used in the CS test analysis

[0089]

[0090]

[0091]

[0092]

[0093]

[0094]

[0095]

[0096]

[0097]

[0098]

[0099]

[0100]

[0101]

[0102]

[0103]

[0104]

[0105]

[0106]

[0107]

[0108]

[0109]

[0110] Sentinel TM HG detection to identify high-grade prostate cancer patients

[0111] For individuals classified as having prostate cancer, a similar method is used to train and validate Sentinel TM High grade (HG), which differentiates GG1+GG2 (low and favorable intermediate-risk cancers) from unfavorable intermediate-risk and high-risk prostate cancers (GG3-GG5). These identified information sequences constitute Sentinel TM the basis for the HG test. Other analyses have shown that the same group of sncRNAs can be used to stratify cancer patients from GG3-5 (high-risk cancers) into GG1+GG2 (low and intermediate-risk cancers). This biostatistical analysis constitutes Sentinel TM the basis for the HG test, which utilizes the 280 sncRNAs identified by the discovery HG test, of which 280 unique sncRNAs: 191 miRNAs and 89 snoRNAs are highly informative.

[0112] Table 3: SEQ ID NO: 561-840 for HG test analysis

[0113]

[0114]

[0115]

[0116]

[0117]

[0118]

[0119]

[0120]

[0121]

[0122]

[0123]

[0124]

[0125]

[0126]

[0127]

[0128]

[0129]

[0130]

[0131]

[0132]

[0133]

[0134] Sentinel TMThe selection of sncRNAs in the PCa, CS, and HG tests is independent of PSA, Gleason score, or pathway analysis and is thus completely unbiased. Since the algorithm was validated using sncRNA levels obtained from an independent training set consisting of participants with positive or negative core needle biopsies (PCa test) or patients labeled with advanced disease (GG3-5) or disease-free for the CS test (no evidence of PCa or GG1-1). (See Tables 4, [000103]-[000104] and Table 5 [000109]-[000110]), this statistical approach minimizes type 1 errors (false negatives) and type 2 errors (false positives), which ensures that the test rigorously differentiates cancer-free from low-grade cancer, low from intermediate-grade cancer, and intermediate from high-grade disease. Based on the algorithm used in the analysis, the described invention has no false negatives and a very low (<5%) false positive rate.

[0135] Based on the above three tests, OpenArray TM platform sequentially interrogates informative RNA entities present in individual sncRNA samples extracted from urine exosomes without compromising the sensitivity and specificity of the three tests.

[0136] In one aspect, the present disclosure provides a method for diagnosing prostate cancer that includes a platform that allows one to distinguish clinically significant tumors from indolent tumors and feeds data based on the subset of interrogated sncRNAs into an algorithm that has been validated based on an independent training data set.

[0137] In one aspect, a method for diagnosing prostate cancer in a male patient includes (1) obtaining a biological sample from the patient, (2) detecting an aggregate expression profile of a collection of signature small non-coding RNAs (sncRNAs) that bind to a plurality of nucleic acids or hybridization probes selected from SEQ ID NO: 1-280; and (3) using the PCa test to correlate the aggregate expression profile of the collection of signature sncRNAs to determine whether the patient is at risk of prostate cancer, i.e., has no evidence of prostate cancer or has prostate cancer.

[0138] In another aspect, the present disclosure provides a method of screening for prostate cancer using the method. In yet another aspect, the present disclosure provides a method for predicting the prostate probability in a subject.

[0139] For patients determined to be at risk of prostate cancer (i.e., determined to have prostate cancer), Sentinel TMA clinically significant (CS) test re-analyzes a sample to distinguish patients with clinically significant or aggressive prostate cancer (GG2-GG5) from patients with clinically insignificant or indolent (GG1) prostate cancer. In one embodiment, a patient is identified as having aggressive prostate cancer when the aggregate or combined expression profile of a plurality or set of signature sncRNAs is greater than or equal to the aggregate expression profile in a prostate cancer biological sample, or a subject is identified as having low-grade prostate cancer when the aggregate expression profile of a set of signature sncRNAs is less than or equal to the aggregate expression profile in a low-grade prostate cancer biological sample.

[0140] In one embodiment, the biological sample includes but is not limited to prostate tissue, blood, plasma, serum, urine, urine supernatant, urinary cell pellet, cerebrospinal fluid, semen, prostate secretions, and prostate cells. In some embodiments, the biological sample is a urine sample. In yet another embodiment, the sample is an exosome isolated from a urine sample. In a preferred embodiment, the sample is sncRNA isolated from exosomes from a urine sample.

[0141] Exosomes are small extracellular vesicles (EVs) that originate from the endosomal compartment of eukaryotic cells. They are present in biological fluids, including blood, urine, semen, and cerebrospinal fluid. The biological origin of exosomes is not well understood; however, it is generally believed that they appear at the point where the early endosomal pathway bifurcates to form late endosomes and multivesicular endosomes, which is the first stage of the exosome pathway. Exosomes contain sncRNAs, which include microRNAs (miRNAs) and small nucleolar RNAs (snoRNAs), which originate from the cytoplasmic and nucleolar regions of the cell, respectively. The presence of exosomes and EVs in the tumor microenvironment has been associated with malignancy in many tumor types, including prostate cancer and other cancers.

[0142] In certain embodiments, the sncRNA isolated from exosomes is derived from semen, blood, prostate secretions, and cerebrospinal fluid. In further embodiments, exosomes are isolated from cancer cells, including prostate cancer cells, lymphocytes, and cells from prostate tissue.

[0143] Methods for isolating exosomes are well known in the art and can be performed using kits such as the Exosome RNA Isolation Kit (Norgen Biotek Corp., Ontario, CA). The yield of sncRNA can be quantified by fluorometry (Qubit, Thermo Fisher Scientific), and the quality of the isolated sncRNA can be assessed using an Agilent 2100 Bioanalyzer.

[0144] RNA extracted from isolated exosomes is a mixture of small RNAs, collectively referred to as small non-coding RNAs (sncRNAs), which include miRNAs, snoRNAs, scaRNAs, siRNAs, snRNAs, and exRNAs. Due to their size (<200 nucleotides), sncRNAs are easily extracted from biological samples, including, for example, formalin-fixed paraffin-embedded (FFPE) tissues or urine. sncRNAs do not degrade during fixation or extraction, avoiding the inherent problems of extracting mRNA from FFPE tissues. A yield of approximately 10 ng of sncRNA from a biological sample is sufficient for multiple analyses using Norgen's Exosome RNA Isolation Kit disclosed above.

[0145] The extracted sncRNAs are reverse transcribed into cDNA, which is more stable than RNA, allowing for longer storage. The resulting cDNA is hybridized to a selected set or collection of characteristic sncRNA probes or a genomic array or microarray chip, such as the miR 4.0 array (ThermoFisher Scientific), for further analysis. The selection of the set of sncRNA probe information is independent of PSA, Gleason score, or biological pathways. The selected set or collection of characteristic sncRNAs includes SEQ ID NO: 1-280, 281-560, and 561-840. The number of sncRNA sequences or probes in the collection is 145-196, preferably not exceeding 280 sncRNA sequences, in order to fit into Sentinel TM PCa, Sentinel TM CS and Sentinel TM in the HG test. By adding up to 280 sncRNA sequences to the algorithm, the test is more precise. Adding more than 280 sncRNA sequences to the analysis does not improve the detection precision.

[0146] Real-time PCR or RT-PCR, commonly referred to as qPCR or RT-qPCR, is used to quantify the absolute amount of a target sequence or compare the relative amounts of a target sequence between samples. RT-qPCR monitors the amplification of the target in real-time through the target-specific (probe) fluorescence signal emitted during the amplification process. Although sequence-specific probes targeting the target are used, background fluorescence occurs during most RT-qPCR reactions, and thus the problem of background fluorescence signal can be addressed by considering two values in real-time PCR: (1) the threshold line (C t ) and (2) the quantification cycle (C q ) value. The threshold line (C t ) is the detection level when the reaction reaches a fluorescence intensity above the background level, i.e., the point (inflection point) where the reaction curve starts the exponential phase. C qThe cycle quantification value, or C q value, is the number of PCR cycles at which the sample reaction curve intersects the threshold line. Thus, the C q value represents how many cycles are needed to detect a true signal from the sample, i.e., the time of event occurrence, where the event is the saturation of fluorescence, representing the maximum level of detection. Since RT-qPCR runs provide a reaction curve for each sample, there will be many C q values. The software in the PCR cycler will calculate the C q value for each sample and plot its graph. The value is inversely proportional to the amount of target nucleic acid in the sample and is related to the number of target copies in the sample. A lower C q value (usually less than 29 cycles) indicates a large amount of the target sequence. In contrast, a higher C q value (more than 38 cycles) indicates a lower amount of the target nucleic acid in the sample. However, the time of event occurrence value can be obtained when the slope of the reaction curve becomes zero, rather than using C TM at the maximum slope. In one embodiment, sncRNA is interrogated using RT-qPCR. In another embodiment, sncRNA is interrogated using qPCR. In a further embodiment, the sncRNA isolated from urinary exosomes is interrogated using an Affymetrix GeneChip

[0147] miRNA 4.0 array according to the manufacturer's instructions.

[0148] These informative sequences (usually 280 sequences) obtained from the training set are then transferred to the OpenArray platform. Patient samples of unknown status are then interrogated on the OpenArray platform, and a Sentinel score is determined using a classification algorithm. The status of the patient is determined by the Sentinel score.

[0149] In one embodiment, the sncRNA levels from unknown prostate cancer patients are interrogated on the OpenArray platform, and then the Sentinel score from patients of unknown disease status can be compared with the scores of the training set to determine the patient's status. TMData obtained from RT-qPCR analysis of sncRNA levels in test samples (test samples) from patients with unknown prostate disease status on a miRNA 4.0 array can be compared to data from healthy patients (without evidence of cancer) or healthy cells obtained from subjects with prostate cancer. Data obtained from analysis of sncRNA levels in test samples can also be compared to clinical baselines established by analyzing healthy (cancer-free) and non-healthy (with urogenital cancer) patients, and the non-healthy patients are further classified into different specific cancer types, which can be further classified into different stages or severities of a specific cancer type (e.g., prostate cancer, etc.) and different stages of a specific disease. In one embodiment, on an Affymetrix GeneChip TM Data obtained from RT-qPCR analysis of sncRNA expression in test samples on a miRNA 4.0 array is compared to data from healthy patients (without evidence of cancer), or the data can also be compared to clinical baselines established by analyzing healthy (cancer-free) and non-healthy (with prostate cancer) patients, and the non-healthy patients are further classified into different stages of prostate cancer (GG1 and GG2-GG5 or GG1+2 and GG3-GG5).

[0150] In some embodiments, the method uses an OpenArray TM technology (ThermoFisher Scientific) to interrogate a panel of sncRNAs (e.g., miRNAs, snoRNAs). The OpenArray TM technology uses a microscope slide-sized plate with 48 subarrays. Each subarray has 64 through-holes, each with a diameter of 300 μm and a depth of 300 μm. The holes are treated with hydrophilic and hydrophobic coatings to retain reagents in the through-holes by surface tension. The OpenArray TMThe technology has 3,072 through-holes (48x64), providing a system that makes real-time PCR studies with a large number of samples, analysis, or both more efficient. Therefore, this system allows for the processing of a large number of samples for gene expression in a short time using trace amounts of samples and reagents. The method employs an algorithm that relies on the expression level of each sncRNA and the grading of biopsies (at least 12 core needle biopsies). In the case of prostate cancer, the method is independent of serum prostate-specific antigen (PSA) levels, Gleason scores (neither of which are meaningful markers of tumor progression), or patient age. The method is also independent of any analysis of biological pathways. This method uses sncRNA isolated from a subject (e.g., urine sample, urinary exosome, or prostate tissue sample) to classify men into those with prostate cancer (indolent (clinically insignificant) or aggressive (clinically significant)) and those without prostate cancer. This method can replace serum PSA as the primary screening method for prostate cancer.

[0151] In one aspect, the present disclosure provides a method for differentiating clinically significant prostate cancer based on the aggregate expression profile of an interrogated set of feature sncRNAs that are classified by an algorithm independent of pathology (Gleason score), tumor volume, or PSA. RNA extracted from biological samples of patients with known cancer outcomes is reverse transcribed and hybridized to a whole-genome array containing sncRNAs (e.g., Affymetrix GeneChip miR 4.0). Small non-coding RNAs that are differentially regulated in clinically significant prostate tumors are identified. In one embodiment, the absolute value of the signal from an open array identifying sncRNAs hybridizing to the probes of SEQ ID NOs: 281 - 561 is compared to the aggregate expression profile found in clinically significant (GG2 - 5) prostate cancer tumors. In another embodiment, the aggregate value of the signal from an open array identifying sncRNAs hybridizing to the probes of SEQ ID NOs: 561 - 840 is compared to the absolute expression profile found in clinically low and favorable intermediate grades (GG1+GG2), as opposed to unfavorable intermediate and high grades (GG3 - GG5) of prostate cancer tumors.

[0152] The disclosed method provides a robust and accurate determination of prostate cancer prognosis within 72 - 96 hours from receipt of a urine sample to obtaining a Sentinel score. In another embodiment, the aggregate expression profile of the identified sncRNAs that bind to SEQ ID NOs: 281 - 560 and 561 - 840 is compared to the aggregate expression profile of sncRNAs in prostate cancer of clinical significance. In another embodiment, the aggregate expression profile of the interrogated sncRNAs that bind to SEQ ID NOs: 281 - 560 and 561 - 840 is compared to the aggregate expression profile of sncRNAs in prostate cancer of clinical significance. In a further embodiment, the aggregate expression profile of the identified sncRNAs that bind to SEQ ID NOs: 281 - 560 and 561 - 840 is compared to the aggregate expression profile of sncRNAs in prostate cancer samples of clinical significance. Thus, appropriate treatment options (or lack thereof) can be initiated.

[0153] The term relative aggregate expression profile is used interchangeably. The aggregate expression profiles of at least a plurality of sncRNAs are combined and compared to the same aggregate expression profile in prostate cancer tissue of clinical significance. In some embodiments, at least 40 sncRNAs are combined and compared to the same aggregate expression profile in prostate cancer tissue of clinical significance. In some embodiments, at least 90 sncRNAs are combined and compared to the same aggregate expression profile in prostate cancer tissue of clinical significance. In some embodiments, at least 150 sncRNAs are combined and compared to the same aggregate expression profile in prostate cancer tissue of clinical significance. In some embodiments, at least 200 sncRNAs are combined and compared to the same aggregate expression profile in prostate cancer tissue of clinical significance. In a preferred embodiment, at least 224 sncRNAs and no more than 280 sncRNAs are combined and compared to the same aggregate expression profile in prostate cancer tissue of clinical significance. In certain embodiments, an aggregate expression profile higher compared to the aggregate expression profile in low - grade prostate cancer tissue indicates that the patient has aggressive prostate cancer and requires treatment. In other embodiments, an aggregate expression profile equal to or lower than the aggregate expression profile in low - grade prostate cancer tissue indicates that the patient does not have aggressive prostate cancer and may require monitoring but not treatment.

[0154] In some embodiments, the aggregate expression profile of the selected sncRNAs is an aggregation of the regulated expression of various types of sncRNAs. The regulated expression can be a decreased or increased expression profile relative to the same sncRNAs in other tissue / tumor types (e.g., healthy prostate tissue, low - grade prostate cancer tissue, or high - grade prostate cancer tissue).

[0155] In other embodiments, the aggregated expression profile of the selected sncRNAs can be an aggregation of the reduced aggregated expression profiles of certain sncRNAs and the increased aggregated expression profiles of other sncRNAs in the same tissue sample. For example, the progression score or aggregated expression profile of a signature sncRNA set can include one or more sncRNAs having a reduced aggregated expression profile relative to another tissue type or other sncRNAs in the same tissue sample, while one or more remaining sncRNAs exhibit an increased aggregated expression level relative to another tissue type or other sncRNAs in the same tissue sample. The aggregated expression profile of the differentially regulated sncRNA set provides an indication of whether a complex, unbiased prostate tumor is clinically significant. Different from other methods that only evaluate the presence or absence or simple increase or decrease of a single target molecule compared to normal tissue, the disclosed method provides a truly unbiased, independent, and multivariate analysis of a prostate tissue sample, thereby allowing surprisingly accurate diagnosis of whether a prostate cancer tumor is clinically significant.

[0156] In some aspects, the method provides for the use of the aggregated expression profile of a signature sncRNA set for monitoring metastasis and cancer staging.

[0157] In another aspect, the present disclosure provides a method for detecting urological malignancies based on the aggregated expression profile of a signature sncRNA set that is interrogated and analyzed using the disclosed classification algorithm. In some embodiments, the malignancy is prostate cancer.

[0158] The present disclosure provides an algorithm-based molecular diagnostic assay for predicting the clinical outcome of prostate cancer patients. The expression levels of one or more sncRNAs can be used alone or arranged into functional gene subsets to calculate a quantitative score that can be used to predict the likelihood of a clinical outcome.

[0159] A "quantitative score" is a numerical value resulting from an arithmetic or mathematical calculation that is used to assist in simplifying or revealing or informing the analysis of more complex quantitative information, such as the correlation between certain expression profiles of the disclosed sncRNAs or subsets of sncRNAs and the likelihood of a clinical outcome in prostate cancer patients. The quantitative score can be determined by applying a specific algorithm. The algorithm used to calculate the quantitative score in the disclosed method can group the expression profile values of the sncRNAs. The grouping of the sncRNAs can be based at least in part on knowledge of the relative contributions of the sncRNAs according to physiological function or component cell characteristics, such as in the groups discussed herein. A quantitative score for the sncRNA group ("sncRNA group score" or Sentinel TMFractions). Additionally, the formation of groups can facilitate the mathematical weighting of the contributions of various aggregated expression profiles of genes or subsets of genes to the quantitative fraction. The weight of an sncRNA or group of sncRNAs representing a physiological process or a cellular characteristic can reflect the contribution of that process or characteristic to cancer pathology and clinical outcomes such as cancer recurrence or progression / staging. The present invention provides a variety of algorithms for calculating the quantitative fraction. For example, the classification algorithms in the present disclosure work in the same way to develop Sentinel fractions for distinguishing different disease states. The classification algorithms select different sncRNA sequences for clinically meaningful and meaningless disease states from a training dataset.

[0160] On the other hand, the selection algorithm tested the correlation of the aggregated expression profiles of urinary exosomal sncRNAs with the pathological stage of the disease (cancer / cancer-free) in a large group of participants with known pathology. The selection algorithm individually evaluated the degree of correlation of each of the 6,599 sncRNAs interrogated on the miR4.0 array with the known pathology of the participants. Then, it repeatedly evaluated all combinations of 2 sncRNAs, 3 sncRNAs, or 4 sncRNAs out of the 6,599 sncRNAs interrogated on the miR 4.0 array, and then used a leave-one-out strategy to examine each individual sncRNA to evaluate the importance of each individual sncRNA in the pathology of the disease. The Sentinel fraction of a patient with an unknown disease state was then determined by interrogating the selected sncRNAs using an Open Array, and the clinical status was determined by comparing the fraction with the fractions in the training dataset. In one embodiment of the present invention, an increase in the quantitative fraction indicates an increased likelihood of a negative clinical outcome.

[0161] Based on the quantitative fraction and the cumulative or absolute or aggregated expression profile, a treatment method can also be determined. Methods for treating prostate cancer include surgery for complete surgical resection of prostate tissue, administration of an effective dose of radiation, and administration of a therapeutically effective amount of a drug for treating prostate cancer, or a combination of the above.

[0162] The algorithm-based assays and associated information provided by the methods of the present invention facilitate optimal treatment decisions for prostate cancer. For example, such a clinical tool would enable physicians to identify patients with a low likelihood of having aggressive cancer and thus would not require further medical intervention other than routine follow-up or active surveillance every 3, 6, or 12 months. Patients without cancer would not require annual medical intervention for follow-up. Patients at risk of developing aggressive cancer would require medical intervention, including but not limited to treatment with one or more chemotherapeutic agents (such as Taxotere, cabazitaxel, docetaxel, mitoxantrone, epirubicin, paclitaxel, and estramustine, etc.), hormone therapy (such as luteinizing hormone-releasing hormone agonists to prevent the production of testosterone, such as leuprolide, goserelin, and triptorelin, or antiandrogen drugs to prevent testosterone from reaching cancer cells, such as bicalutamide and nilutamide), immunotherapy, radiation, cryotherapy, surgery, or a combination thereof.

[0163] The disclosed methods are used to monitor patients undergoing treatment to determine the patient's response to treatment. In one aspect, the present disclosure provides a method for determining a patient's response to treatment, comprising: (i) obtaining a biological sample from the patient, (ii) detecting an aggregate expression profile of a set of features of small non-coding RNAs (sncRNAs) from the biological sample, wherein the set of sncRNAs comprises SEQ ID NOs: 1-280, 281-560, and 561-840, (iii) correlating the aggregate expression profile of the sncRNAs of SEQ ID NOs: 1-280, 281-560, and 561-840 in the subject after treatment by comparing it with that before treatment, and (iv) determining whether the patient is responsive to the treatment and whether there is a need to modify the treatment. In one embodiment, the method further compares the resulting aggregate expression profile of the set of features of sncRNAs from (iii) above and then compares it with the aggregate expression profile of the set of features of sncRNAs from a large training data set of a target population of patients with prostates having known grade groups to determine (a) whether the patient's prostate cancer is stable (no significant change compared to the grade group), (b) whether the patient is responsive to the treatment, i.e., the patient has improved (the results show the tumor is similar to a tumor with a lower grade group), or (c) the patient is non-responsive (when the results show the tumor is similar to a tumor with a higher grade group, the patient has gotten worse), based on the aggregate expression profile of the set of signature sncRNAs and the Sentinel score of that grade group, and whether there is a need to modify the treatment. Treatment modifications include but are not limited to adjusting the concentration or dosage of chemotherapeutic agents, radiation, immunotherapeutic agents, or hormones administered, adding or removing one or more agents used.

[0164] In another aspect, the present disclosure provides a method for determining disease recurrence, disease progression, or likelihood of survival based on the aggregated expression profiles of a set of feature sncRNAs comprising SEQ ID NO: 1 - 280, 281 - 560, and 561 - 840 by comparing the aggregated expression profiles of SEQ ID NO: 1 - 280, 281 - 560, and 561 - 840 in a training dataset and an early profile of a patient.

[0165] In another aspect, the present disclosure provides a system for determining whether a patient has cancer or has cancer and classifying subjects with cancer into (i) indolent (low - grade, GG1), (ii) medium or high - grade (GG2 - GG5), (iii) low / medium - risk (GG1 - GG2), or (iv) aggressive (high - grade, GG3 - GG5) prostate cancer. The system includes at least three processors configured to (a) interrogate information sequences of sncRNA sequences, (b) determine and compare Sentinel scores to determine whether a subject has prostate cancer or does not have prostate cancer, and classify subjects determined to have cancer into respective grade groups, such as low - grade, medium / high - grade, low / medium - risk, or aggressive - grade cancer. Subjects determined to have no evidence of cancer do not require medical intervention and will return for a follow - up once a year. Subjects determined to have low - grade or low / medium - grade prostate cancer do not require medical intervention except for regular follow - up or active surveillance every 3, 6, or 12 months, and subjects determined to have medium / high - grade or aggressive prostate cancer require medical intervention.

[0166] Examples

[0167] This and other aspects of the invention are further illustrated by the following non - limiting examples.

[0168] Example 1

[0169] Study population:

[0170] Two independent patient cohorts were used to develop and validate Sentinel TM PCa and Sentinel TM CS test. For developing Sentinel TM PCa, the clinical and demographic characteristics of 233 participants used to classify patients as having cancer or not having cancer were based on statistical analysis of a set of feature snRNAs. For patients classified as having cancer, Sentinel was used TMThe CS test differentiates patients with GG1 (indolent, low-risk cancer) from GG2-5 (moderate, high-risk, and aggressive cancers, respectively), and this is also based on statistical analysis of another set of features of sncRNAs using a second classification algorithm to classify tumors as GG1 versus GG2-5. The sncRNAs in both tests were interrogated by Affymetrix miR 4.0 arrays.

[0171] Urine collection and processing

[0172] For the development of Sentinel TM Urine samples for the PCa and CS tests and for the US-based retrospective study cohort were collected on the day of the visit at two clinical sites for clinical examination: Albany Medical Center (Albany, NY, USA) and SUNY Downstate Medical Center (Brooklyn, NY, USA). The remaining samples for the retrospective study were obtained from GUBioBank, University Health Network in Toronto, Canada, and were shipped frozen in bulk at -20 °C to the miR Science laboratory. With institutional review board approval, patient information was collected and anonymized at each participating site. The diagnosis of prostate cancer was obtained by histopathological grading of core needle biopsies; the percentage of tumor in each core and the number of positive cores were used to assess the grade group (GG).

[0173] Centrifuge urine samples to remove free cells and debris. Extract RNA using an exosome RNA isolation kit (Norgen Biotek, ON) according to the manufacturer's instructions. The sncRNA yield was quantified by fluorometry (Qubit, Thermo Fisher Scientific), and the RNA samples were stored at -80 °C until analysis.

[0174] Microarray analysis of total exosomal sncRNA

[0175] Use Affymetrix GeneChip according to the manufacturer's instructions TMmiR 4.0 arrays interrogated sncRNAs. Raw MAIME-compliant data files for 235 patients analyzed on these arrays have been deposited in NCBI's Gene Expression Omnibus. (Edgar R et al. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acid Res 2002 30:207). 6599 sncRNAs in the training set were interrogated on Affymetrix GeneChip TM miRNA 4.0 arrays.

[0176] Small non-coding RNA entities interrogated for each participant were analyzed using proprietary selection and classification algorithms. Information-rich sequences for differentiating cancer and non-cancer subjects (SEQ ID NO: 1 - 280) and between grade group 1 and grade group 2 - 5 patients were identified. (SEQ ID NO: 281 - 842)

[0177] Exosome sncRNA interrogation based on QuantStudio OpenArray TM

[0178] cDNA synthesis, pre-amplification of selected miRNAs: To analyze exosomal miRNAs, total sncRNA was reverse transcribed in separate reactions with three specific miRNA stem-loop primer pools using the TaqMan TM MicroRNA Reverse Transcription Kit (Thermo Fisher Scientific). miRNA cDNA pools were enriched for 16 cycles (95°C for 10 minutes, 55°C for 2 minutes, 72°C for 2 minutes, 95°C for 15 seconds, and 60°C for 4 minutes repeated 16 cycles, 99.9°C for 10 minutes) with Pre-Amp primer pools and interrogated on three 56-entity subarrays on the QuantStudio OpenArray TM

[0179] cDNA synthesis, pre-amplification, and interrogation of selected snoRNAs: Total sncRNA was reverse transcribed using a high-capacity cDNA reverse transcription kit with a single Pre-Amp primer pool (Thermo Fisher Scientific) according to the manufacturer's recommendations. snoRNA cDNA products were enriched by pre-amplification (95 °C for 10 minutes, 95 °C for 15 seconds and 60 °C for 4 minutes, repeated 14 and 18 cycles respectively, and 99 °C for 10 minutes) and interrogated in two 56-entity subarrays.

[0180] Statistical analysis:

[0181] Sentinel TM The PCa test is based on a classification algorithm that has been trained on a group of participants with positive or negative core needle biopsies. The classification algorithm takes the sncRNA expression profile of a participant with an unknown disease state as input and produces a Sentinel TM score; participants are classified by comparing the Sentinel TM PCa score with a pre-determined cut-off value that maintains the sensitivity of classifying patients with an unknown future disease state (but known expression profile) at a user-defined level (95% or higher). A second classification algorithm, Sentinel TM CS test, operates similarly to the Sentinel TM PCa test. However, the classification algorithm for the Sentinel TM CS test is trained on groups of patients labeled as low-grade (GG1) and those labeled as favorable intermediate to high-grade prostate cancer (GG2-GG5). A third classification algorithm, Sentinel TM HG test, is trained on groups of patients identified as low-risk and favorable intermediate-risk (GG1+GG2) prostate cancer and a second group characterized as unfavorable intermediate-risk and high-risk (GG3-GG5).

[0182] Sentinel TM The test paradigm runs in two or three tiers. First, it uses the sncRNA profile in the participant's urine as input into the classification rules of the Sentinel TM PCa test to determine the presence of cancer; second, for those patients diagnosed with cancer, the Sentinel TM CS test determines whether the cancer is low-risk (GG1); third, the Sentinel TM HG test determines whether the tumor is unfavorable intermediate or high-risk (GG3-GG5). (See Figure 4 )

[0183] Table 4: Demographic and clinical characteristics of the groups used to develop the classification algorithm.

[0184]

[0185] * In the exempt research status, PSA levels were not available for patients without evidence of cancer.

[0186] Table 4 established the training dataset for developing the Sentinel TM test. Among 235 patients, the patients included in the "no cancer" group (89 patients) were carefully selected from age-matched men (n = 58) who presented at the urology clinic for problems unrelated to urologic oncology and men (n = 30) who had undergone one or more 12-core diagnostic needle biopsies that showed no evidence of prostate cancer (NEPC).

[0187] The patients in the "cancer" group (n = 146) were selected based on the histopathology of the core needle biopsy. Among the 146 "cancer" group, 90 patients were classified as GG1 cancer and 56 patients were classified as GG2-5.

[0188] Among the 6,599 microarray sequences from the training dataset queried using a proprietary selection algorithm to separate the results "informative" from those that were not, only 400 - 600 were informative. The results refer to the sncRNA sequences that affect the algorithm when each sequence is added to predict whether a subject with an unknown disease state has prostate cancer and the cancer stage (indolent vs. aggressive).

[0189] The statistical analysis used was based on the ability to identify sequences with hidden associations with the results, which were only observable after conditioning on other sequences. Among the 400 - 600 informative sncRNA sequences, 280 sncRNA sequences were used for the classification algorithm as the basis for defining the expression signatures of the Detect PCa test ( Figure 5 ), the Detect HG test ( Figure 7 ), and the Detect CS test ( Figure 6 ). Then a subset of the informative sncRNAs considered to be of the highest importance was determined for each test (respectively Figure 5 、 7 and 6 (right small figure)).

[0190] These 280 sncRNAs were combined to design the OpenArray TM platform, which provided the basis for the Sentinel TM PCa and CS tests. The Sentinel TMThe PCa test combines the aggregate expression profiles of 84 unique sncRNAs: 60 miRNAs and 24 snoRNAs, to classify subjects with unknown disease status as having prostate cancer or not having prostate cancer. Similarly, Sentinel TM The CS test utilizes 135 unique sncRNAs: 105 miRNAs and 30 snoRNAs, to classify subjects with prostate cancer as having GG1 (indolent) prostate cancer or GG2-GG5 (aggressive) prostate cancer. Additionally, 61 sncRNAs (25 miRNAs and 36 snoRNAs) provide information in both tests. OpenArray TM The platform sequentially interrogates informative RNA entities present in individual sncRNA samples extracted from urine exosomes without compromising the sensitivity and specificity of the two tests.

[0191] Example 2

[0192] Validate Sentinel in a case-control patient cohort TM PCa, Sentine1 TM CS and Sentinel TM HG test

[0193] Using the OpenArray TM platform for Sentinel TM PCa and Sentinel TM The performance characteristics of the CS test were established in a case-control study of 1436 patients (Table 5).

[0194] Table 5: Demographics and clinical characteristics of case-control samples used to validate Sentinel TM PCa and Sentinel TM HG tests.

[0195]

[0196] *In the exempt research status, individual patients without evidence of cancer did not have PSA levels available, and all patients had levels below 3.0 ng / mL.

[0197] Sentinel TM The performance characteristics of the PCa test were determined in a case-control cohort of 600 men, whose demographics are shown in Table 5. Sentinel TM A scatter plot of the PCa scores is shown in Figure 8 A, and the corresponding receiver operating curve (ROC) curve is in Figure 8 C. As summarized in Table 6, SentinelTM The PCa test correctly classified 281 / 300 patients as having cancer and 275 / 300 patients as not having cancer (sensitivity 93.7%, specificity 91.7%).

[0198] The performance characteristics of the Sentinel were determined in a test cohort of 600 men TM CS test. The scatter plot of the Sentinel TM CS scores is shown in Figure 9 A, and the corresponding receiver operating characteristic (ROC) curve is in Figure 9 C. As summarized in Table 6, the Sentinel TM CS test correctly classified 143 / 154 patients as high grade (GG3 - GG5) and 132 / 143 correctly as non - high grade (sensitivity 92.9%, specificity 90.4%).

[0199] The performance characteristics of the Sentinel were determined in a test cohort of 600 men TM HG test. The scatter plot of the Sentinel TM HG scores is shown in Figure 10 A, and the corresponding receiver operating characteristic (ROC) curve is in Figure 10 C. As summarized in Table 6, the Sentinel TM CS test correctly classified 94 / 100 patients as high grade (GG3 - GG5) and 191 / 200 correctly as non - high grade (GG1 + GG2) (sensitivity 94%, specificity 95.5%).

[0200] Table 6: Sentinel TM PCa, Sentinel TM CS and Sentinel TM HG test's empirical sensitivity, specificity, PPV, and NPV

[0201] <![CDATA[Sentinel TM PCa]]> 1 - error rate Numerator Denominator Proportion 95% lower CI 95% upper CI Sensitivity 281 300 0.937 0.905 0.960 Specificity 275 300 0.917 0.882 0.944 PPV 281 306 0.918 0.884 0.945 NPV 275 294 0.935 0.903 0.959 <![CDATA[Sentinel TM CS]]> 1 - error rate Numerator Denominator Proportion 95% lower CI 95% upper CI Sensitivity 143 154 0.929 0.880 0.962 Specificity 132 146 0.904 0.848 0.944 PPV 143 157 0.911 0.859 0.948 NPV 132 143 0.923 0.871 0.959 <![CDATA[Sentinel TM HG]]> 1 - error rate Numerator Denominator Proportion 95% lower CI 95% upper CI Sensitivity 94 100 0.940 0.880 0.975 Specificity 191 200 0.955 0.919 0.978 PPV 94 103 0.913 0.846 0.956 NPV 191 197 0.970 0.938 0.987

[0202] * NPV, or negative predictive value, is the probability that an individual does not have the specific disease after a negative test result.

[0203]

[0204] ** The sensitivity of a test is the proportion of people with the disease who test positive among all those who actually have the disease.

[0205]

[0206] *** The specificity of the test is the proportion of people who test negative among all those who actually do not have the disease.

[0207]

[0208] **** The PPV or positive predictive value is the probability that an individual truly has a specific disease after a positive test result.

[0209]

[0210] Example 3

[0211] Using the Sceintific Sentinel TM Study on the safety and scientific validity of identifying clinically insignificant PCa using the platform.

[0212] The purpose of the clinical study is to verify the Scientific Sentinel TM PCa test and the Scientific Sentinel TM Performance characteristics of the CS test to (1) identify prostate cancer patients in men aged 50 - 80 years with a needle biopsy for suspected prostate cancer, and (2) distinguish men with clinically significant prostate cancer (grade 2 or above) from those with clinically insignificant prostate cancer (grade group 1) in men aged 50 - 80 years. These classifications will be compared with the results of core needle biopsy and radical prostatectomy (if available). Sensitivity, specificity, positive and negative predictive values will be determined. This study is a prospective, observational and non - intervention study. Informed participants will provide two or more urine samples during the study and agree to share relevant anonymized clinical data with the research team.

[0213] Participants aged between 50 and 80 years, with a core needle biopsy for suspected prostate cancer and otherwise meeting the inclusion and exclusion criteria, will be enrolled and provide urine samples for the Sentinel TM PCa / CS test. The study will evaluate the Sentinel TM PCa test and the Sentinel TM CS test characteristics based on the disclosed method, which uses a classification algorithm to identify future prostate cancer patients and classify prostate cancer as clinically significant or clinically insignificant.

[0214] "Gold standard" assessment of cancer from the results of core needle biopsies: Participants with no positive cores will be designated as "cancer-free"; participants with cancer in one or more cores will be designated as having "clinically insignificant" prostate cancer if the histopathology of all cores with cancer is no greater than grade group 1; participants will be designated as having "clinically significant" prostate cancer if any core has grade groups 2-5.

[0215] Each enrolled study participant will be followed for one year. Participants will provide urine samples during each visit, and all relevant clinical data will be obtained, including repeat biopsy, PSA results, and the pathology report of radical prostatectomy (if administered as part of clinical care). Follow-up results (if any) will be used for outcome analysis. For each urine sample provided, Sentinel TM PCa and CS tests will be determined and compared with the available 1-year follow-up outcome data to inform the sensitivity, specificity, positive, and negative predictive values of the tests.

[0216] The classification algorithm uses a function by controlling the sensitivity at or above a pre-specified level (denoted as 1-α); for example, the assumed value in this design is α = 0.05, so the sensitivity in the population is at least 95%. Note that the value of α represents the false negative rate of the test, i.e., for patients with true positives, the test is (incorrectly) negative.

[0217] To describe how to calculate the cut-off value of the Sentinel TM PCa score to control the sensitivity, for each participant in the training dataset, the Sentinel TM PCa score will be calculated using the remaining members of the training dataset and only his small non-coding RNA (sncRNA) sequences; that is, the true disease state of each patient in the training dataset will be hidden, thus mimicking the setting of future patient classification. Then the cut-off value used in the Sentinel TM PCa test is calculated so that the empirical sensitivity for patients with prostate cancer in the training dataset corresponds to the upper one-sided 95% confidence interval of the population sensitivity for future patients of at least 1-α.

[0218] Using this cut-off value of the Sentinel TM PCa score pre-determined from the training dataset, the corresponding values of sensitivity, specificity, positive, and negative predictive values, as well as the upper limit of the corresponding 95% confidence interval, will be calculated based on the expected participant data accumulated in this proposed study, where each biopsy result is hidden, i.e., only the sncRNA sequences of the participants are used. Note that these error rates refer to the classification of future patients with unknown disease status.

[0219] Any patents, patent application publications or scientific publications cited in this application are incorporated by reference in their entirety. Sequence Listing <110> Merck Science LLC M. Tyneswood A.G. DiLianzo W-L.W. Wang <120> Methods for Predicting Prostate Cancer and Their Uses <130> P-586001-PC <150> 62 / 978,184 <151> 2020-02-18 <150> 62 / 819,325 <151> 2019-03-15 <160> 840 <170> PatentIn version 3.5 <210> 1 <211> 22 <212> RNA <213> Homo sapiens <400> 1 caaaaaccgg caauuacuuu ug 22 <210> 2 <211> 65 <212> RNA <213> Homo sapiens <400> 2 gagaaugggg ggacagaugg agaggacaca ggcuggcacu gagguccccu ccacuuuccu 60 ccuag 65 <210> 3 [[ID=5*]]<211> 86 <212> RNA .*END]]<213> Homo sapiens <400> 3 gagggaaagc aggccaaccu cgaggaucuc cccagccuug gcguucaggu gcugaggaga 60 ucgucgaggu uggccugcuu ccccuc 86 <210> 4 <211> 82 <212> RNA <213> Homo sapiens <400> 4 ggauuguggg gggucgcucu aggcaccgca gcacugugcu ggggauguug cagcugccug 60 ggagugacuu cacacagucc uc 82 <210> 5 <211> 84 <212> RNA <213> Homo sapiens <400> 5 auuagguugg uauaaaauua auugcaguuu uugucauuac uuucaauagc aaaaacugca 60 guuacuuuug caccaaugua auac 84 <210> 6 <211> 22 <212> RNA <213> Homo sapiens <400> 6 ugagguagua gguugugugg uu 22 <210> 7 <211> 75 <212> RNA <213> Homo sapiens <400> 7 uggaccaaug augugaaugg aaugcaucug aauaaaaauu augaucaauc aguuuuugga 60 acaacugagg uccac 75 <210> 8 <211> 96 <212> RNA <213> Homo sapiens <400> 8 agauaaaucu auagacaaaa uacaaucccg gacaacaaga agcuccuaua gcuccuguag 60 cuucuugugc ucuaggauug uauuuuguuu auauau 96 <210> 9 <211> 21 <212> RNA <213> Homo sapiens <400> 9 cacauuacac ggucgaccuc u 21 <210> 10 <211> 17 <212> RNA <213> Homo sapiens <400> 10 uggggcucag cgaguuu 17 <210> 11 <211> 93 <212> RNA <213> Homo sapiens <400> 11 uaaguguaaa cuuaaggacu gucuuuucua agccugugcc uugccuuucc uuuggcacag 60 gcuuagaaaa gacagucuuu aaguuuacac uuc 93 <210> 12 <211> 63 <212> RNA <213> Homo sapiens <400> 12 gaaggccucu gcaggguuug cuuugaggua cuuccuuccu gucaacccug uucuggaguc 60 ugu 63 <210> 13 <211> 22 <212> RNA <213> Homo sapiens <400> 13 gaucccuuua ucuguccucu ag 22 <210> 14 <211> 22 <212> RNA <213> Homo sapiens <400> 14 uuggguuuuc ucuucaaucc ag 22 <210> 15 <211> 21 <212> RNA <213> Homo sapiens <400> 15 cuuagauuag aggauauugu u 21 <210> 16 <211> 18 <212> RNA <213> Homo sapiens <400> 16 cagccccaca gccucaga 18 <210> 17 <211> 67 <212> RNA <213> Homo sapiens <400> 17 uacaggccgg ggcuuugggu gagggacccc cggagucugu cacggucuca ccccaacucu 60 gccccag 67 <210> 18 <211> 134 <212> RNA <213> Homo sapiens <400> 18 uugcacagug aacacccaag ugugcuuuau aguucccuug gcuuugaccc ugugcuagag 60 cauugccugc ucuucuccuc ugcauuaaaa ggaauauuua uccuuuuaaa uguauucaga 120 aagccagcac auua 134 <210> 19 <211> 65 <212> RNA <213> Homo sapiens <400> 19 cuccucuggg gguggggggc ugggcguggu ggacagcgau gcaucccucg ccuucucacc 60 cucag 65 <210> 20 <211> 67 <212> RNA <213> Homo sapiens <400> 20 guggcacuca aacugugggg gcacuuucug cucucuggug aaagugccgc caucuuuuga 60 guguuac 67 <210> 21 <211> 79 <212> RNA <213> Homo sapiens <400> 21 cugacuccag uguccaggcc aggggcagac aguggacaga gaacagugcc caagaccacu 60 ggacuuggag ucaggacau 79 <210> 22 <211> 22 <212> RNA <213> Homo sapiens <400> 22 uggggaggug uggagucagc au 22 <210> 23 <211> 103 <212> RNA <213> Homo sapiens <400> 23 augaccugug aaaccaaggg cuccuaaugc uaugaccaaa gacugaagcu cucuaugaga 60 ugccagccac ucaauagugc acuuuuucug agaagauaua aga 103 <210> 24 <211> 103 <212> RNA <213> Homo sapiens <400> 24 gugucggcug uggcgugacu gucccucugu gucccccacu aggcccacug cucaguggag 60 cguggaggac gaggaggagg ccguccacga gcaaugccag cau 103 <210> 25 <211> 22 <212> RNA <213> Homo sapiens <400> 25 gugugcggaa augcuucugc ua 22 <210> 26 <211> 110 <212> RNA <213> Homo sapiens <400> 26 ugaguuuuga gguugcuuca gugaacauuc aacgcugucg gugaguuugg aauuaaaauc 60 aaaaccaucg accguugauu guacccuaug gcuaaccauc aucuacucca 110 <210> 27 <211> 22 <212> RNA <213> Homo sapiens <400> 27 cagcagcaau ucauguuuug aa 22 <210> 28 <211> 82 <212> RNA <213> Homo sapiens <400> 28 gacaggauuc caguacaggu cucucauuuc cuucaugauu aggaauacua cuuugaaaug 60 agagaccugu acuguaucug uu 82 <210> 29 <211> 19 <212> RNA <213> Homo sapiens <400> 29 agagcuggcu gaagggcag 19 <210> 30 <211> 22 <212> RNA <213> Homo sapiens <400> 30 ugcccuaaau gccccuucug gc 22 <210> 31 <211> 102 <212> RNA <213> Homo sapiens <400> 31 uuauuuuugu aguugaugaa ugugcugauu ggguauucuc gugugugugu gaggugccac 60 ccucaaacuu uguuaugaug uuggcacauu acccaucuga ua 102 <210> 32 <211> 22 <212> RNA <213> Homo sapiens <400> 32 auggccagag cucacacaga gg 22 <210> 33 <211> 21 <212> RNA <213> Homo sapiens <400> 33 cgagccucaa gcaagggacu u 21 <210> 34 <211> 23 <212> RNA <213> Homo sapiens <400> 34 ugccccaccu gcugaccacc cuc 23 <210> 35 <211> 70 <212> RNA <213> Homo sapiens <400> 35 aaagugagug augaauaguu cuguggcaua ugaaucauua auuuugauua aacccuaaac 60 ucugaagucc 70 <210> 36 <211> 21 <212> RNA <213> Homo sapiens <400> 36 caacaccagu cgaugggcug u 21 <210> 37 <211> 104 <212> RNA <213> Homo sapiens <400> 37 auccuuuugu gguucauaag caugaugauc agguuuucag gcauaugugu acgaugugcc 60 uccuucaaac uuuguuagga ugcuaccacg cuacccaucu gacu 104 <210> 38 <211> 23 <212> RNA <213> Homo sapiens <400> 38 agaacucuug cagucuuaga ugu 23 <210> 39 <211> 58 <212> RNA <213> Homo sapiens <400> 39 ugcuggcuca uuucauaugu gugcugagaa aauucacaca uaugaaguga gccagcac 58 <210> 40 <211> 67 <212> RNA <213> Homo sapiens <400> 40 gugcauauga uggaaaaguu uuaaucuccu gacacuugug augucuucaa aggaaccacu 60 gaugcac 67 <210> 41 <211> 87 <212> RNA <213> Homo sapiens <400> 41 accgcaggga aaaugaggga cuuuuggggg cagauguguu uccauuccac uaucauaaug 60 ccccuaaaaa uccuuauugc ucuugca 87 <210> 42 <211> 71 <212> RNA <213> Homo sapiens <400> 42 uggaucaaug augaccacug guggcguaug agucauaugu gaugaauacg ugucuggaac 60 ucugaggucc a 71 <210> 43 <211> 88 <212> RNA <213> Homo sapiens <400> 43 ugaguuuugg gaugagaccc uggaauaagu gcuggacaca gugccugaau cagacugugg 60 aaauauuaau guauuuuauu uuuacuua 88 <210> 44 <211> 77 <212> RNA <213> Homo sapiens <400> 44 uuccagcccg aggccucugu gacgucacgg ugucugcggg aggagaccau gacgucacag 60 aggcuucgcg cucugag 77 <210> 45 <211> 21 <212> RNA <213> Homo sapiens <400> 45 ccuguugaag uguaaucccc a 21 <210> 46 <211> 71 <212> RNA <213> Homo sapiens <400> 46 uggaucgaug gugacuguug auggcauaug acucacauau gaugaguacg uaucuggaac 60 ucugaggucu g 71 <210> 47 <211> 98 <212> RNA <213> Homo sapiens <400> 47 auccuuuugu acuugguaag caugaugauu ggguuuuuau gcuuauauau gagacaugcu 60 ugucucaaau cuuguuacag cacauuaccc uuccuacu 98 <210> 48 <211> 21 <212> RNA <213> Homo sapiens <400> 48 ucuaguaaga guggcagucg a 21 <210> 49 <211> 71 <212> RNA <213> Homo sapiens <400> 49 ggcucaaucu cugguccugc agccuucugc cuuuggcuuu cugaagcgag cugaacuaga 60 gauugggccc a 71 <210> 50 <211> 103 <212> RNA <213> Homo sapiens <400> 50 guccuuuugu aguccauaag cauggugauu ugguuucaug cucauguguc agauaugcuu 60 cccucaaacc uuguuacagc aucaucacau uaccuguuug aug 103 <210> 51 <211> 75 <212> RNA <213> Homo sapiens <400> 51 uucuuacaaa ucuaaaugug cuuugaugca aguauauuug aaucccuuuc caucugauaa 60 cugagcaaaa uaaua 75 <210> 52 <211> 22 <212> RNA <213> Homo sapiens <400> 52 uaauacuguc ugguaaaacc gu 22 <210> 53 <211> 22 <212> RNA <213> Homo sapiens <400> 53 aacaauaucc uggugcugag ug 22 <210> 54 <211> 19 <212> RNA <213> Homo sapiens <400> 54 aggugugucu guagagucc 19 <210> 55 <211> 20 <212> RNA <213> Homo sapiens <400> 55 cuacaaaggg aagcccuuuc 20 <210> 56 <211> 75 <212> RNA <213> Homo sapiens <400> 56 gucagaugau uugaauugau aagcugaugu ucugugaggu acaaaaguua auagcauguu 60 agaguucuga uggca 75 <210> 57 <211> 22 <212> RNA <213> Homo sapiens <400> 57 caaucacuaa cuccacugcc au 22 <210> 58 <211> 20 <212> RNA <213> Homo sapiens <400> 58 aaaacugcag uuacuuuugc 20 <210> 59 <211> 215 <212> RNA <213> Homo sapiens <400> 59 aaaauuauac uuucagcaau caucucuaua guuuguuacu agagaagcuu cugugaaugu 60 guagagcacc ggaaaccaca aggcaaaggc ucagcauucu cuccuaagcg cgaagcuggc 120 uccugguguu gguuggccgc aacugccauu ugccauugau gaucauucuu cucuuccugu 180 gguagaggaa gagggagaga augcaguuug agugg 215 <210> 60 <211> 104 <212> RNA <213> Homo sapiens <400> 60 auccuucugu aguucgugag caugaugauu gggugcucac acacauaugu gagauguacc 60 acccucaaac cuuguuacaa ugucagcaca uuacccaucu gacc 104 <210> 61 <211> 21 <212> RNA <213> Homo sapiens <400> 61 agagaagaag aucagccugc a 21 <210> 62 <211> 82 <212> RNA <213> Homo sapiens <400> 62 uuuuuuuguu gcuugucuug guuuuaugcc uuuuaugugc cuugauauaa aaggcauaaa 60 accaagacaa gcaacagaaa aa 82 <210> 63 <211> 60 <212> RNA <213> Homo sapiens <400> 63 gagcaggcga ggcugggcug aacccguggg ugaggagugc agcccagcug aggccucugc 60 <210> 64 <211> 21 <212> RNA <213> Homo sapiens <400> 64 cugaccuaug aauugacagc c 21 <210> 65 <211> 22 <212> RNA <213> Homo sapiens <400> 65 acuuuaacau ggaagugcuu uc 22 <210> 66 <211> 23 <212> RNA <213> Homo sapiens <400> 66 ugucacucgg cucggcccac uac 23 <210> 67 <211> 22 <212> RNA <213> Homo sapiens <400> 67 ccuggcauau uugguauaac uu 22 <210> 68 <211> 22 <212> RNA <213> Homo sapiens <400> 68 ugucaguuug ucaaauaccc ca 22 <210> 69 <211> 104 <212> RNA <213> Homo sapiens <400> 69 auccuguuau gauucauaag caugaugacu gaguuuucac acuccugugu gagaugugcc 60 ucccucuaac cuuauuacaa cauugacauc uuacucauuu gaca 104 <210> 70 <211> 22 <212> RNA <213> Homo sapiens <400> 70 aacccguaga uccgaacuug ug 22 <210> 71 <211> 22 <212> RNA <213> Homo sapiens <400> 71 cguguucaca gcggaccuug au 22 <210> 72 <211> 72 <212> RNA <213> Homo sapiens <400> 72 cuaaaacaau gucaauaguu uucaucaaca gcaguugaac cuaguaagug ucgauacuuu 60 gggucugagu gg 72 <210> 73 <211> 23 <212> RNA <213> Homo sapiens <400> 73 agugccugag ggaguaagag ccc 23 <210> 74 <211> 131 <212> RNA <213> Homo sapiens <400> 74 cccuccuaca aaggcauguc uauaguuccu ugucuuugga cauguaagaa uuggaggcaa 60 agaaaugugg acuuggagaa aucuggggcc agcuugcucu ccgcaggcuc aagaucaacc 120 aucccacaua g 131 <210> 75 <211> 23 <212> RNA <213> Homo sapiens <400> 75 ugugcuugcu cgucccgccc gca 23 <210> 76 <211> 22 <212> RNA <213> Homo sapiens <400> 76 ugggaaagag aaagaacaag ua 22 <210> 77 <211> 22 <212> RNA <213> Homo sapiens <400> 77 uuaacuccuu ucacacccau gg 22 <210> 78 <211> 22 <212> RNA <213> Homo sapiens <400> 78 uaccugggag acugagguug ga 22 <210> 79 <211> 65 <212> RNA <213> Homo sapiens <400> 79 cuguaaugau guugcucaaa uaucugaccu gaaaugauua uauagaccaa uuuaauacug 60 aagaa 65 <210> 80 <211> 133 <212> RNA <213> Homo sapiens <400> 80 uagcaagccu ccagcgugcu ugggucugcg gugacccuau gcauuccuuc agugcuugcu 60 agaacaguuu ugaaacgguu ugaggccuug cccugcucca uccagagcaa gguuauagaa 120 auuucagaca aug 133 <210> 81 <211> 20 <212> RNA <213> Homo sapiens <400> 81 auauggguuu acuaguuggu 20 <210> 82 <211> 86 <212> RNA <213> Homo sapiens <400> 82 aaccuaugua ucauaucaca uuggguuuuc augcucaugu gugagaagug ccucuuucaa 60 accuuguucu gacacauuau cuuaca 86 <210> 83 <211> 20 <212> RNA <213> Homo sapiens <400> 83 ugggcugcug agaaggggca 20 <210> 84 <211> 75 <212> RNA <213> Homo sapiens <400> 84 guuuaaagaa uacugugaau uucacuguca caaauucaaa uaaagugaga guggaauuca 60 caguauuuaa ggaau 75 <210> 85 <211> 82 <212> RNA <213> Homo sapiens <400> 85 cugacuuuuu uagggaguag aagggugggg agcaugaaca auguuucuca cucccuaccc 60 cuccacuccc caaaaaaguc ag 82 <210> 86 <211> 20 <212> RNA <213> Homo sapiens <400> 86 ucugguccug gacaggaggc 20 <210> 87 <211> 141 <212> RNA <213> Homo sapiens <400> 87 ggucucuugu gucggcaccu ggguggcuug ccgcccacac aaccaaauua aaaaauaaca 60 cagaagggua agguaagucu ccauuaaacc caggaaagag acuggaaaac uccucuuugg 120 agccugucua uagucacagg u 141 <210> 88 <211> 87 <212> RNA <213> Homo sapiens <400> 88 agcgguggcc agugucauuu uugugauguu gcagcuagua auaugagccc aguugcauag 60 ucacaaaagu gaucauugga aacugug 87 <210> 89 <211> 20 <212> RNA <213> Homo sapiens <400> 89 aggaggacaa guugugggau 20 <210> 90 <211> 22 <212> RNA <213> Homo sapiens <400> 90 agcaaaauaa gcaaauggaa aa 22 <210> 91 <211> 67 <212> RNA <213> Homo sapiens <400> 91 cugguccauu ucccugccau ucccuuggcu ucaauuuacu cccagggcug gcagugacau 60 gggucaa 67 <210> 92 <211> 22 <212> RNA <213> Homo sapiens <400> 92 agaaagggug gcaauaccuc uu 22 <210> 93 <211> 97 <212> RNA <213> Homo sapiens <400> 93 uauuaugcca ugacauugug ucaauaugcg augauguguu gugauggcac agcgucauca 60 cguggugacg caacaucaug acguaagacg ucacaac 97 <210> 94 <211> 60 <212> RNA <213> Homo sapiens <400> 94 ucggcuaagg aaguccugug cucaguuuug uagcaucaaa acuaggauuu cucuuguuac 60 <210> 95 <211> 99 <212> RNA <213> Homo sapiens <400> 95 uggcggccug ggcgggagcg cgcgggcggg gccggccccg cugccuggaa uuaaccccgc 60 ugugcuugcu cgucccgccc gcagcccuag gcggcgucg 99 <210> 96 <211> 104 <212> RNA <213> Homo sapiens <400> 96 auccuuuugu aauacauaag cauaaugauu ggguuuuuau guucacaugu uugauaugcc 60 ucccucaaau ccucuuauga ugucggcaca uuacccaucu gagg 104 <210> 97 <211> 18 <212> RNA <213> Homo sapiens <400> 97 ugaggcgggg gggcgagc 18 <210> 98 <211> 66 <212> RNA <213> Homo sapiens <400> 98 agggcugggc uggcagggca agugcugcag aucuuugucu aagcagcccc ugccuuggau 60 cuccca 66 <210> 99 <211> 22 <212> RNA <213> Homo sapiens <400> 99 aguuugggau ggagagagga ga 22 <210> 100 <211> 22 <212> RNA <213> Homo sapiens <400> 100 agcgagguug cccuuuguau au 22 <210> 101 <211> 17 <212> RNA <213> Homo sapiens <400> 101 uaagugcuuc caugcuu 17 <210> 102 <211> 22 <212> RNA <213> Homo sapiens <400> 102 uaggggcagc agaggaccug gg 22 <210> 103 <211> 20 <212> RNA <213> Homo sapiens <400> 103 ccuccugccc uccuugcugu 20 <210> 104 <211> 72 <212> RNA <213> Homo sapiens <400> 104 acuccaugau gaacccaaaa ugccaaguau augacugaac uuacaaguga uaccaucuua 60 cgacugaaga gu 72 <210> 105 <211> 90 <212> RNA <213> Homo sapiens <400> 105 augcuuuugu aguucguaag caugaugauu ggguuuucuu gcucuuguau gagaugugcc 60<L uccgucauac cuuggaaacc ugacuugaaa 90 <210> 106 <211> 21 <212> RNA <213> Homo sapiens <400> 106 uuggagggug uggaagacau c 21 <210> 107 <211> 20 <212> RNA <213> Homo sapiens <400> 107 aaguccugcu ucuguugcag 20 <210> 108 <211> 75 <212> RNA <213> Homo sapiens <400> 108 gcagugccuu acucagaaag gugccaguca cuuacacuac augucacugu guccuuucug 60 cguagaguaa ggcuc 75 <210> 109 <211> 110 <212> RNA <213> Homo sapiens <400> 109 acaaggguuc uaauuucacu acauccccuc caauauuugg uaucuuuccu uucuuaaaaa 60 aauagccagc cuagugagug ugaaguggca ucucaaugug guuuugauuu 110 <210> 110 <211> 139 <212> RNA <213> Homo sapiens <400> 110 ugcacugcgu gguaucugca cucagcaguu uacuccugcu aggguguuca aaggucagug 60 ccauagaaau ccaguaucug guuucauugg uuuucuuggc uuugugcuug uuaaaccugg 120 uauuucuauu gauacagca 139 <210> 111 <211> 100 <212> RNA <213> Homo sapiens <400> 111 auacuuuugu aggucauaag cugaggauug gguuuucaug cucuugugug agauaugcuu 60 cucucaaacc uucugaccug ggcacauuac ccagcuaaug 100 <210> 112 <211> 189 <212> RNA <213> Homo sapiens <400> 112 uuucuauagu uuauuaccag aaaaguuucu cagaaugugu agagcacugg aaaccaugag 60 gaagaggcau agcguucucu cuugagcauc aaguuggcug uugguguugc uuugcugcaa 120 acgccauuug ucauugucuu ccuugucuuc cuuuaggaga guaagaggga gaggacacag 180 ucuggguag 189 <210> 113 <211> 22 <212> RNA <213> Homo sapiens <400> 113 cacccccugu uuccuggccc ac 22 <210> 114 <211> 80 <212> RNA <213> Homo sapiens <400> 114 gcucugauuu acuucugucc ggcaugguga acagcaggau uggcuguagc uguucucuuu 60 gccaaggaca gaucugaucu 80 <210> 115 <211> 22 <212> RNA <213> Homo sapiens <400> 115 gguucccucu ccaaaugugu cu 22 <210> 116 <211> 84 <212> RNA <213> Homo sapiens <400> 116 ggccaguguu gagaggcgga gacuugggca auugcuggac gcugcccugg gcauugcacu 60 ugucucgguc ugacagugcc ggcc 84 <210> 117 <211> 106 <212> RNA <213> Homo sapiens <400> 117 auccuuuugu aguucauaaa ugugauaauu ggguguucac gugcauguau gagaugucug 60 agucccucaa accuuguuac aacauuggua cauuacccau uuuacc 106 <210> 118 <211> 20 <212> RNA <213> Homo sapiens <400> 118 gauauucaga ggcuaggugg 20 <210> 119 <211> 22 <212> RNA <213> Homo sapiens <400> 119 cuauacaguc uacugucuuu cc 22 <210> 120 <211> 21 <212> RNA <213> Homo sapiens <400> 120 uuccuucugu ugucugugca g 21 <210> 121 <211> 65 <212> RNA <213> Homo sapiens <400> 121 gacauguggg guuugcugua gacauuucag auaacucggg auucuguagc uuccuggcaa 60 cuuug 65 <210> 122 <211> 107 <212> RNA <213> Homo sapiens <400> 122 auccuuuugu aguuuauaag cgugaugacu gggguuucac gugcaugugu gaaaugugcc 60 uuccccaagc cuuguuauga ccucauugga acauuacccc uuugaca 107 <210> 123 <211> 21 <212> RNA <213> Homo sapiens <400> 123 caccgacucu gucuccugca g 21 <210> 124 <211> 19 <212> RNA <213> Homo sapiens <400> 124 ggccuuguuc cugucccca 19 <210> 125 <211> 22 <212> RNA <213> Homo sapiens <400> 125 ucugccaucc ucccuccccu ac 22 <210> 126 <211> 23 <212> RNA <213> Homo sapiens <400> 126 uugggauggu aggaccagag ggg 23 <210> 127 <211> 92 <212> RNA <213> Homo sapiens <400> 127 uuaguuccag ccuccuggcu caccuggaac cauuucuccu gggaagcaug guagccagga 60 gaguggauuc caggugguga gggcuuggua cu 92 <210> 128 <211> 23 <212> RNA <213> Homo sapiens <400> 128 caacggaauc ccaaaagcag cug 23 <210> 129 <211> 25 <212> RNA <213> Homo sapiens <400> 129 ggcggaggga aguagguccg uuggu 25 <210> 130 <211> 22 <212> RNA <213> Homo sapiens <400> 130 uaguucuucc cuuugcccaa uu 22 <210> 131 <211> 65 <212> RNA <213> Homo sapiens <400> 131 cuguuaaugc uaaucgugau agggguuuuu gccuccaacu gacuccuaca uauuagcauu 60 aacag 65 <210> 132 <211> 24 <212> RNA <213> Homo sapiens <400> 132 cccggacagg cguucgugcg acgu 24 <210> 133 <211> 103 <212> RNA <213> Homo sapiens <400> 133 auccuuuugu aguucaucag ugucaugagu ggguuuucac gcacaugugu caaauaugcc 60 ucccucaaac uguuacguca uuggcauauu accugacgug aag 103 <210> 134 <211> 23 <212> RNA <213> Homo sapiens <400> 134 ccggggcaga uugguguagg gug 23 <210> 135 <211> 23 <212> RNA <213> Homo sapiens <400> 135 ucagcaccag gauauuguug gag 23 <210> 136 <211> 22 <212> RNA <213> Homo sapiens <400> 136 ucaaguaguu ucaugauaaa gg 22 <210> 137 <211> 22 <212> RNA <213> Homo sapiens <400> 137 ugcucagguu gcacagcugg ga 22 <210> 138 <211> 73 <212> RNA <213> Homo sapiens <400> 138 ugaaucaaug gugaccacug guggcauaua agucauggau gaugaauaug agaagaaaag 60 aaucuagguu uuu 73 <210> 139 <211> 111 <212> RNA <213> Homo sapiens <400> 139 auccuuuugu gguucauccg ccugaugauu ggguuuucau gcagacgugu gagcugugcc 60 ucccucaagc cuuguuacaa cauccgacau ccgcacauua ccugucugau g 111 <210> 140 <211> 111 <212> RNA <213> Homo sapiens <400> 140 ccacgguccu aguuaaaaag gcacauuccu agacccugcc ucagaacuac ugaacagagu 60 cacugggugu ggaguccagg aaucugcauu uuuaccccua ucgcccccgc c 111 <210> 141 <211> 24 <212> RNA <213> Homo sapiens <400> 141 ccucacccag cucucuggcc cucu 24 <210> 142 <211> 22 <212> RNA <213> Homo sapiens <400> 142 aaucauacag ggacauccag uu 22 <210> 143 <211> 97 <212> RNA <213> Homo sapiens <400> 143 uagccaguca gaaaugagcu uauucauaaa agugcaguau ggugaaguca aucuguaauu 60 uuauguauaa gcuagucucu gauugaaaca ugcagca 97 <210> 144 [[ID=⑥]]<211> 22 [[ID=⑧]]<212> RNA [[ID=⑩]]<213> Homo sapiens <400> 144 acugggaaga ggagcugagg ga 22 <210> 145 <211> 79 <212> RNA <213> Homo sapiens <400> 145 ccgggacuuu guggguucug accccacuug gaucacgccg acaacacugg ucuugaaguc 60 agaacccgca aaguccugg 79 <210> 146 <211> 72 <212> RNA <213> Homo sapiens <400> 146 cugccucuga ugaagccugu guugguaggg acaucugaga guaaugauga augccaaccg 60 cucugauggu gg 72 <210> 147 <211> 21 <212> RNA <213> Homo sapiens <400> 147 ugauauguuu gauauugggu u 21 <210> 148 <211> 81 <212> RNA <213> Homo sapiens <400> 148 Note: In the translation, the numbers and tags are kept as they are, and the text in Chinese characters is translated into English according to the context. For the convenience of distinction, the Arabic numerals in the original text are replaced by Chinese numerals in the translation process, and then restored to Arabic numerals after translation. If you have any other questions, please feel free to let me know.aguugguggg ggagccauga gauaagagca ccuccuagag aauguugaac uaaaggugcc 60 cucucuggcu ccuccccaaa g 81 <210> 149 <211> 99 <212> RNA <213> Homo sapiens <400> 149 auucuuaaau gaaugaugaa auaccaaaaa gaaaaauaag caaagaacag auaacagaaa 60 gaagcacagc aaauacaaca uaauacugac aguaaaaau 99 <210> 150 <211> 75 <212> RNA <213> Homo sapiens <400> 150 auggauuuga uugaaugauu cucccauuuc cacauggaga guggagccca gagaauuguu 60 uaaucaugua uccau 75 <210> 151 <211> 24 <212> RNA <213> Homo sapiens <400> 151 gcugguuuca uauggugguu uaga 24 <210> 152 <211> 62 <212> RNA <213> Homo sapiens <400> 152 gggggugggg cuagugaugc aggacgcugg ggacuggaga aguccugccu gacccugucc 60 ca 62 <210> 153 <211> 143 <212> RNA <213> Homo sapiens <400> 153 aagcauggca cacuggaugg gcguucugcu ucucuuuaaa gagcauggau uuauccauac 60 caugugacau gaaugaaaug aggaguuuuc agggcugcca accucuuggu uaagguucug 120 uguaguauau uucuccuaca aua 143 <210> 154 <211> 72 <212> RNA <213> Homo sapiens <400> 154 uggaccaaug augagaauau gucaugaacc aaggaauaug auuaauccaa uucuguguac 60 uggaggguca aa 72 <210> 155 <211> 21 <212> RNA <213> Homo sapiens <400> 155 agaaguggcu aauaauauug a 21 <210> 156 <211> 69 <212> RNA <213> Homo sapiens <400> 156 uagcccaggg cuuggagugg ggcaagguug uuggugauau ggcuuccucu cccuuccugc 60 ccuggcuag 69 <210> 157 <211> 23 <212> RNA <213> Homo sapiens <400> 157 acggaauaug uauacggaau aua 23 <210> 158 <211> 79 <212> RNA <213> Homo sapiens <400> 158 auuaauaugg aagggagaag agcuuuaaug cucugaaaau gacuccaauc auuaaagcuc 60 uucucccuuc cauauuaau 79 <210> 159 <211> 76 <212> RNA <213> Homo sapiens <400> 159 gccaacugca gaucauggga cugucucagc cccauaugua ucugaaggcu gagaaguccc 60 augauccgca cuuggc 76 <210> 160 <211> 22 <212> RNA <213> Homo sapiens <400> 160 aguggggugg gacccagcug uu 22 <210> 161 <211> 22 <212> RNA <213> Homo sapiens <400> 161 aagcugccag uugaagaacu gu 22 <210> 162 <211> 23 <212> RNA <213> Homo sapiens <400> 162 cccuucccuc acucuucucu cag 23 <210> 163 <211> 133 <212> RNA <213> Homo sapiens <400> 163 ucccaucucu uaaauaaaaa gauuuuuuuu uuaagaaguu guacaugugc aauggcugca 60 aacagcagcu uccuuggcag ugugugcagc cuguuucuug uauggguugc ucuaagggac 120 cuuggagaca ggc 133 <210> 164 <211> 20 <212> RNA <213> Homo sapiens <400> 164 gggcuggggc gcggggaggu 20 <210> 165 <211> 17 <212> RNA <213> Homo sapiens <400> 165 gccggacaag agggagg 17 <210> 166 <211> 134 <212> RNA <213> Homo sapiens <400> 166 ucaucaggug ggauaauccu uaccuguucc ucguuuugga gggcagauag aacaggauaa 60 uuggaguuug caugauccau gauuaauguc ucuguguaau caggacuugc aaacucugau 120 uguucauauc ugau 134 <210> 167 <211> 21 <212> RNA <213> Homo sapiens <400> 167 uucacagugg cuaaguuccg c 21 <210> 168 <211> 22 <212> RNA <213> Homo sapiens <400> 168 acuggggagc agaaggagaa cc 22 <210> 169 <211> 19 <212> RNA <213> Homo sapiens <400> 169 uugaucucgg aagcuaagc 19 <210> 170 <211> 50 <212> RNA <213> Homo sapiens <400> 170 cuucucuuuc caguucuucc cagaauuggg aaaagcuggg uugagagggu 50 <210> 171 <211> 65 <212> RNA <213> Homo sapiens <400> 171 uauuguugug ggugggcaga agucuguuuu cuucaugguu uucugaccuu ugccucuccc 60 cucag 65 <210> 172 <211> 22 <212> RNA <213> Homo sapiens <400> 172 caaggagacg ggaacaugga gc 22 <210> 173 <211> 81 <212> RNA <213> Homo sapiens <400> 173 auucaggccg guccugcaga gaggaagccc uuccaauacc uguaagcaga agggcuuccu 60 cucugcagga ccggccugaa u 81 <210> 174 <211> 104 <212> RNA <213> Homo sapiens <400> 174 aucuuuuugu gguucacaag ugugaugauu agguuuucag acucaugugu gagacaugcc 60 uuccucaaac cuucuuaugc uaucagcaca uaaucuggcu gaca 104 <210> 175 <211> 23 <212> RNA <213> Homo sapiens <400> 175 uaaauuucac cuuucugaga agg 23 <210> 176 <211> 139 <212> RNA <213> Homo sapiens <400> 176 gagcuuccag gaucaccccu gcagaguggc uaauauucug ccagcuucgg aaagggaggg 60 gaagcaagcc uggcagaggc acccauucca uucccagcuu gcuuaguagc uggccauggg 120 aagacacugu gcaacacug 139 <210> 177 <211> 69 <212> RNA <213> Homo sapiens <400> 177 ucuuagugau gaaaacuuug uccaguucug cuaaugacuu uaagugauga uaaacuaugu 60 cugagggga 69 <210> 178 <211> 140 <212> RNA <213> Homo sapiens <400> 178 auccaaggcg auucccucuc caaggggaca ucuagugccc cucucaggaa aguagcaacu 60 uggaauagaa ucuggcaugc cuaaggucuu ugaggaacag ggaugcuuau uuccucugcc 120 uuccuuggcu gccuacauag 140 <210> 179 <211> 22 <212> RNA <213> Homo sapiens <400> 179 agcucugcug cucacuggca gu 22 <210> 180 <211> 133 <212> RNA <213> Homo sapiens <400> 180 uagcaagccu ccagcgugcu ugggucugca gugaccccgu ggauuccuac agggcuugcc 60 agaacaguuu ugaaaugguu ugaggccuug ccgugcucca uguagagcaa gguuauagaa 120 auuucagaca aug 133 <210> 181 <211> 20 <212> RNA <213> Homo sapiens <400> 181 ucacucucac cuugcuuugc 20 <210> 182 <211> 94 <212> RNA <213> Homo sapiens <400> 182 uggaucgaug augacuuuca uacaugcauu ccuuggaaag cugaacaaaa ugagugaaaa 60 cucuauaccg ucauccucgu cgaacugagg ucca 94 <210> 183 <211> 96 <212> RNA <213> Homo sapiens <400> 183 ccugaagagg ugcaugaagc cugguccugc ccucacuggg aacccccuuc ccucugggua 60 ccagacagaa uucuaugcac uuuccuggag gcucca 96 <210> 184 <211> 23 <212> RNA <213> Homo sapiens <400> 184 gcgaggaccc cucggggucu gac 23 <210> 185 <211> 211 <212> RNA <213> Homo sapiens <400> 185 aagacucuac ucucagggcu cauuucuguc auucaauacu agagaaguuu cucugaaugu 60 uuagagcacu ggaaaccaaa cggaggaggc gggcauucuu uccugagcau gcagccagcu 120 cauaguguug uuuuguugca gcugccgcuu gccauugaug auccuucuuc ucuuccuuca 180 ggggaguaag gagacgacgc ggucuuagug g 211 <210> 186 <211> 23 <212> RNA <213> Homo sapiens <400> 186 ucuaaagacu agacuucgcu aug 23 <210> 187 <211> 137 <212> RNA <213> Homo sapiens <400> 187 aagacuacac uuucagggau aauuucuaua guucauuacu agagaaguuu cucugaaugu 60 guagagcacc auaaaauaca uuuuauuuuu uauuugagac agggucucac ucugucaccc 120 aagcuggagu gcagugg 137 <210> 188 <211> 86 <212> RNA <213> Homo sapiens <400> 188 ccugccugca gaaaggagcu auccacucca gguguccuuu cuucugagag cuggacacuu 60 guugggauga ccugccugca gguagg 86 <210> 189 <211> 22 <212> RNA <213> Homo sapiens <400> 189 auucucucug gaucccaugg au 22 <210> 190 <211> 68 <212> RNA <213> Homo sapiens <400> 190 cucaggcuca guggugcaug cuuauagucc cagccacucu ggaggcugaa ggaagauggc 60 uugagccu 68 <210> 191 <211> 27 <212> RNA <213> Homo sapiens <400> 191 uggucuguuc auucucucuu uuuggcc 27 <210> 192 <211> 96 <212> RNA <213> Homo sapiens <400> 192 auccuucugu ggcugauaug ugugaugagg ggguuuucac acucuugcgu gggacgugca 60 accucuuuag aacaguggca cauuaccugu ccuaca 96 <210> 193 <211> 84 <212> RNA <213> Homo sapiens <400> 193 gcguacagug ccuuucucaa ggaggugucg uuuaugugaa cuaaaauaua aauuucaccu 60 uucugagaag aguaauguac agca 84 <210> 194 <211> 20 <212> RNA <213> Homo sapiens <400> 194 ucuuuucuuu gagacucacu 20 <210> 195 <211> 23 <212> RNA <213> Homo sapiens <400> 195 uugggaggga agacagcugg aga 23 <210> 196 <211> 69 <212> RNA <213> Homo sapiens <400> 196 auguaauaau guucaucaaa ugucugaccu gaaaugagca uguagacaag uuaauuuaac 60 acugaagaa 69 <210> 197 <211> 96 <212> RNA <213> Homo sapiens <400> 197 gcuccaguaa caucuuaaag uaaauaugca ccaaaauuac uuuugguaaa uacaguuuug 60 gugcauauuu acuuuaggau guuacuggag cuccca 96 <210> 198 <211> 142 <212> RNA <213> Homo sapiens <400> 198 cugcagccua uuaagccaac ugaguuccuu uccucauggg ggggcccagu gugcaauggc 60 ugcaaacagc agcuuccuug guaguguaug cagccugugu guuguauugu auggguugcu 120 cuaagggacc cuggagacag uc 142 <210> 199 <211> 22 <212> RNA <213> Homo sapiens <400> 199 agcuacaguu acuuuugcac ca 22 <210> 200 <211> 22 <212> RNA <213> Homo sapiens <400> 200 agacaguagu ucuugccugg uu 22 <210> 201 <211> 22 <212> RNA <213> Homo sapiens <400> 201 gggaggugug aucucacacu cg 22 <210> 202 <211> 22 <212> RNA <213> Homo sapiens <400> 202 aacucacgaa guauaccgaa gu 22 <210> 203 <211> 19 <212> RNA <213> Homo sapiens <400> 203 ucugaggugg aacagcagc 19 <210> 204 <211> 22 <212> RNA <213> Homo sapiens <400> 204 ggauuccugg aaauacuguu cu 22 <210> 205 <211> 211 <212> RNA <213> Homo sapiens <400> 205 aauuguauac uuucagggau cauuccauag guuguuacua gagaaguuuu uuuagaugug 60 uagaacacug gaaaccacga ggaggaggcg cagcauucuc ucuugaccau gaagccggcu 120 cuugguguug uuucauugca acugucauuu gccauugaug aucguucucu uccucuggga 180 gaguaagagg gagaggacac aguuugagug g 211 <210> 206 <211> 102 <212> RNA <213>智人 <400> 206 auccauuugu aguucagaaa caugacuauu gucuuuucaa gcuuauauuga gaucuggcuc 60 squirrel squirrel squirrel ug 102 <210> 207 <211> 77 <212> RNA <213>智人 <400> 207 cucuugguau gaacucugu guguucaugu cucucugugc acaggggacg agagucacug 60 Auguchuguag Project 77 <210> 208 <211> 82 <212> RNA <213>智人 <400> 208 gggucauga ugagaaccuu auauuguucu gagagaggu gaugacuuaa aaucaugcu 60 Caauggau Acggcugaggc cc 82 <210> 209 <211> 22 <212> RNA <213>智人 <400> 209 auagggug ugaauuuacc oh 22 <210> 210 <211> 23 <212> RNA <213>智人 <400> 210 cunccauuug ouuugaugau gga 23 <210> 211 <211> 23 <212> RNA <213> Homo sapiens <400> 211 auacacauac acgcaacaca cau 23 <210> 212 <211> 69 <212> RNA <213> Homo sapiens <400> 212 accaccagug augaguugaa uacugcccca gucugaucaa caugcgugaa agauauuuuc 60 ugagcugug 69 <210> 213 <211> 22 <212> RNA <213> Homo sapiens <400> 213 ucgcgguuug ugccagauga cg 22 <210> 214 <211> 22 <212> RNA <213> Homo sapiens <400> 214 ugucuuacuc ccucaggcac au 22 <210> 215 <211> 85 <212> RNA <213> Homo sapiens <400> 215 ggcuguggag gcaccaguau uucugaaauu cuuuuuucug aaauucuuca ggaaggauuu 60 cagaaauacu ggugucccga cagcc 85 <210> 216 <211> 67 <212> RNA <213> Homo sapiens <400> 216 gcaugacucu ucaaccucag gacuugcaga auuaauggaa ugcuguccua agguuguuga 60 guugugc 67 <210> 217 <211> 21 <212> RNA <213> Homo sapiens <400> 217 auuugugcuu ggcucuguca c 21 <210> 218 <211> 70 <212> RNA <213> Homo sapiens <400> 218 auacaugaug acuuacaugg acucucauuc agcuaaugac uugcugcuga aacauggaaa 60 ucugauuuuu 70 <210> 219 <211> 22 <212> RNA <213> Homo sapiens <400> 219 uuccugggcu ucuccucugu ag 22 <210> 220 <211> 22 <212> RNA <213> Homo sapiens <400> 220 caggaugugg ucaaguguug uu 22 <210> 221 <211> 73 <212> RNA <213> Homo sapiens <400> 221 ccagagaugg gaaggccuuc cggugauuau cacagccaug ccuuuaccuc cagaaggccu 60 uuccaucucu guc 73 <210> 222 <211> 20 <212> RNA <213> Homo sapiens <400> 222 gagacagguu caugcugcua 20 <210> 223 <211> 104 <212> RNA <213> Homo sapiens <400> 223 auccuuuugu aguucauaag cuugauguuu gaguuuucac acuuacgugu gaaaugugcc 60 ucccuuaaac cuuguuacua cgucagcaca uuacccauga gaca 104 <210> 224 <211> 82 <212> RNA <213> Homo sapiens <400> 224 guguugauga ugagaaccuu auauuauccu gaagagaggu gaugacuuaa aaaucaugcu 60 caauaggauu acgcugaggc cc 82 <210> 225 <211> 65 <212> RNA <213> Homo sapiens <400> 225 cuaggaggga ugggagagag gacugugagg cauggguggc ucuaugguca cgcccaucuu 60 ccuac 65 <210> 226 <211> 71 <212> RNA <213> Homo sapiens <400> 226 cucaccagug augaguugaa uaccgcccca gucugaucaa ugugugacug aaagguauuu 60 ucugagcugu g 71 <210> 227 <211> 207 <212> RNA <213> Homo sapiens <400> 227 uccaacgugg auacacccgg gaggucacuc uccccgggcu cuguccaagu ggcguagggg 60 agcauagggc ucugccccau gauguacaag ucccuuucca caacguugga aauaaagcug 120 ggccucgugu cugcgccugc auauuccuac agcuucccag aguccugucg acaauuacug 180 gggagacaaa ccaugcagga aacagcc 207 <210> 228 <211> 80 <212> RNA <213> Homo sapiens <400> 228 aggcagcaaa uggccagagc ucacacagag ggaugagugc acuucaccug cagugugacu 60 cagcaggcca acagaugcua 80 <210> 229 <211> 81 <212> RNA <213> Homo sapiens <400> 229 cuucuggaag cugguuucac augguggcuu agauuuuucc aucuuuguau cuagcaccau 60 uugaaaucag uguuuuagga g 81 <210> 230 <211> 86 <212> RNA <213> Homo sapiens <400> 230 uagaauauuu cggcauucua gaugagagau auauauauac cucauaugua uaugguauac 60 cucaucuaga augcuguaau auucua 86 <210> 231 <211> 98 <212> RNA <213> Homo sapiens <400> 231 cagagaggag cugccacuug ggcacugaaa caauguccau uaggcuuugu uauggaaacu 60 ucuccugauc auuguuuugu guccauugag cuuccaau 98 <210> 232 <211> 115 <212> RNA <213> Homo sapiens <400> 232 ccaccuucag cugaguguag ugcccuacuc cagagggcgu cacucaugua aacuaaaaca 60 ugauuguagc cuuuuggagu agaguaauac acaucacgua acgcauauuu ggugg 115 <210> 233 <211> 131 <212> RNA <213> Homo sapiens <400> 233 cccuccuaca aaggcauguc uauaauuccu ugucuuugga cauguaagaa uuggagggac 60 agaaaugugg acuuggagaa aucuggggcc agcuuucuca ucacaggcuc aacaucaacc 120 augccacaua g 131 <210> 234 <211> 22 <212> RNA <213> Homo sapiens <400> 234 uccuaaaucu gaaaguccaa aa 22 <210> 235 <211> 73 <212> RNA <213> Homo sapiens <400> 235 cucugccucc cgugccuacu gagcugaaac acaguugguu uguguacacu ggcucaguuc 60 agcaggaaca ggg 73 <210> 236 <211> 22 <212> RNA <213> Homo sapiens <400> 236 uuagggcccu ggcuccaucu cc 22 <210> 237 <211> 103 <212> RNA <213> Homo sapiens <400> 237 auccuuuugu gguucauuag cuugauauug gguuuucaca cuauucuaug agaugugccu 60 cccucaaaac uuguuacaac auugacacau uacccuucug aug 103 <210> 238 <211> 22 <212> RNA <213> Homo sapiens <400> 238 accugagguu gugcauuucu aa 22 <210> 239 <211> 128 <212> RNA <213> Homo sapiens <400> 239 ggggugcacu cagggcaggg ggcuugaaga acggcuccuc uguuuacgac acacucaaca 60 ggggugugag gucacaguga ugagaggccc aaacuugugg ccuccccgug aacaaaugcc 120 cuacacau 128 <210> 240 <211> 86 <212> RNA <213> Homo sapiens <400> 240 ugaugacacu cucuggaauu guuacacuac cauaauuaaa gugcacugaa ucuuuuucua 60 ucugaugggg ggggaauaaa auaauu 86 <210> 241 <211> 21 <212> RNA <213> Homo sapiens <400> 241 ugagccucuc cuucccucca g 21 <210> 242 <211> 20 <212> RNA <213> Homo sapiens <400> 242 ccugcguguu uucuguccaa 20 <210> 243 <211> 107 <212> RNA <213> Homo sapiens <400> 243 uaccaacccc auggaauuuu uacucaccuu cagucaacug auuugcucuu ugguggagau 60 auucagaggc uagguggaga uagagguagc cuugagggug ggugugg 107 <210> 244 <211> 21 <212> RNA <213> Homo sapiens <400> 244 agcggugcuc cugcgggccg a 21 <210> 245 <211> 21 <212> RNA <213> Homo sapiens <400> 245 cagcggagcc uggagagaag g 21 <210> 246 <211> 22 <212> RNA <213> Homo sapiens <400> 246 cuuggauuuu ccugggccuc ag 22 <210> 247 <211> 105 <212> RNA <213> Homo sapiens <400> 247 auccucuugc aguucauaag caugaugauu ggguuuucac acuccugugu gaaauguacc 60 uuccucaaac cuuuuuauaa caucagcaca uuaccgaaca ugaaa 105 <210> 248 <211> 68 <212> RNA <213> Homo sapiens <400> 248 gacucggcug cgguggacaa guccggcucc agaaccugga caccgcucag ccggccgcgg 60 cagggguc 68 <210> 249 <211> 92 <212> RNA <213> Homo sapiens <400> 249 accuaccuaa cuggguuagg gcccuggcuc caucuccuuu aggaaaaccu ucugugggga 60 guggggcuuc gacccuaacc caggugggcu gu 92 <210> 250 <211> 63 <212> RNA <213> Homo sapiens <400> 250 uacggaugag caaagaaagu gguuucuuaa aauggaaucu acucuuugug aagaugcugu 60 gaa 63 <210> 251 <211> 77 <212> RNA <213> Homo sapiens <400> 251 ggucaaugau gagcugacau guauucugaa ucuaaaguug auuauuagua cuuuaguucu 60 agaauuacug agacaug 77 <210> 252 <211> 18 <212> RNA <213> Homo sapiens <400> 252 [[ID= forty-two]]cuggagucua ggauucca 18 <210> 253 <211> 21 <212> RNA <213> Homo sapiens <400> 253 cuucuugugc ucuaggauug u 21 <210> 254 <211> 21 <212> RNA <213> Homo sapiens <400> 254 uuagugaagg cuauuuuaau u 21 It should be noted that there may be some inaccuracies in the translation due to the lack of clear context for these sequences. This translation is mainly based on literal conversion.<210> 255 <211> 22 <212> RNA <213> Homo sapiens <400> 255 ucggcucucu cccucacccu ag 22 <210> 256 <211> 22 <212> RNA <213> Homo sapiens <400> 256 uuuggucccc uucaaccagc ua 22 <210> 257 <211> 129 <212> RNA <213> Homo sapiens <400> 257 uuauuuaucu gacagaccug cagcaguuac uggaugcugu uaaaguuucc acuacagaug 60 caagaaaagu gucccacacu uucugucugu cugauuguga cagcuaagau uaaaucaggu 120 aggacagua 129 <210> 258 <211> 71 <212> RNA <213> Homo sapiens <400> 258 uauuccaaug augcaagugu gucgugaacu aaggauuaug auuaauccag uuuuguagcu 60 agagggauuu u 71 <210> 259 <211> 21 <212> RNA <213> Homo sapiens <400> 259 aguggcaaag ucuuuccaua u 21 <210> 260 <211> 86 <212> RNA <213> Homo sapiens <400> 260 gugacuccca gggacugccu uaggagaaag uuucuggaau gucagaacuu ccagaaacuu 60 ucuccuaagg cagucccugg agucac 86 <210> 261 <211> 74 <212> RNA <213> Homo sapiens <400> 261 gguuggugca aaaguaacug cgguuuuugc cuuucaacau aauggcaaaa cccacaauua 60 cuuuugcacc aauc 74 <210> 262 <211> 83 <212> RNA <213> Homo sapiens <400> 262 agucugugau gaauugcuuu gacuucugac accucguaug aaaacugcac gugcagucug 60 auuauuuagc aagacugagg cuu 83 <210> 263 <211> 93 <212> RNA <213> Homo sapiens <400> 263 ccggggagaa guacggugag ccugucauua uucagagagg cuagauccuc uguguugaga 60 aggaucauga ugggcuccuc gguguucucc agg 93 <210> 264 <211> 91 <212> RNA <213> Homo sapiens <400> 264 guucuagagc augguuucuc aucauuugca cuacugauac uuggggucag auaauuguuu 60 gugguggggg cuguuguuug cauuguagga u 91 <210> 265 <211> 22 <212> RNA <213> Homo sapiens <400> 265 uuggggaaac ggccgcugag ug 22 <210> 266 <211> 135 <212> RNA <213> Homo sapiens <400> 266 cugcagccaa uuaagccaac ugaguuccuu uccuuguggg ggcccagugu gcaauggcug 60 cacacagcag cuuccuuggu aguguacaca gccuguuggu uguauggguu gcucugaggg 120 accuuggaga caggc 135 <210> 267 <211> 18 <212> RNA <213> Homo sapiens <400> 267 ugcuuccuuu cucagcug 18 <210> 268 <211> 23 <212> RNA <213> Homo sapiens <400> 268 ugguucucuu guggcucaag cgu 23 <210> 269 <211> 80 <212> RNA <213> Homo sapiens <400> 269 uauaaaucua guggaaacau uucugcacaa acuagauucu ggacaccagu gugcggaaau 60 gcuucugcua cauuuuuagg 80 <210> 270 <211> 66 <212> RNA <213> Homo sapiens <400> 270 aaagcuggau acucagucau ggucauugua acaugauagu gacagguacu ggguaagacu 60 gcauag 66 <210> 271 <211> 22 <212> RNA <213> Homo sapiens <400> 271 aagugcuguc auagcugagg uc 22 <210> 272 <211> 212 <212> RNA <213> Homo sapiens <400> 272 aaugcuauac uuucaugggu cauuucuaua guuuguuauu agagaaguuu cucugaaugu 60 guugagcacc agaaaccacg aggagaugca gcauucucuc cugaacggga agccagcuuu 120 uggcauugcu uugaugcaac uaccauuugc cauugauggc aaugcaucgc uuccucuagg 180 aguguaagag ggaguggaug cagucagagu gg 212 <210> 273 <211> 76 <212> RNA <213> Homo sapiens <400> 273 agguuggugc aaaagugauu gcaguguuug ccaauaaaag uaaugacaaa aacugcaguu 60 acuuuugcac cagccc 76 <210> 274 <211> 23 <212> RNA <213> Homo sapiens <400> 274 aggagguggu acuaggggcc agc 23 <210> 275 <211> 69 <212> RNA <213> Homo sapiens <400> 275 ucucagugau gaaaacuuug uccaguucug cuacugacag uaagugaaga uaaagugugu 60 cugaggaga 69 <210> 276 <211> 79 <212> RNA <213> Homo sapiens <400> 276 acuguccuuu uucgguuauc augguaccga ugcuguauau cugaaaggua caguacugug 60 auaacugaag aaugguggu 79 <210> 277 <211> 69 <212> RNA <213> Homo sapiens <400> 277 ccauuuuaga ggcuggaaua gagauucuug aggcuuggaa gaguaaggau cccuuuaucu 60 guccucuag 69 <210> 278 <211> 22 <212> RNA <213> Homo sapiens <400> 278 uccugcguag gaucugagga gu 22 <210> 279 <211> 23 <212> RNA <213> Homo sapiens <400> 279 ucgaggacug guggaagggc cuu 23 <210> 280 <211> 141 <212> RNA <213> Homo sapiens <400> 280 ccucauuuuc uuggcaggaa cuuguagucc cacucccugu uauguacaga ggcaaaggga 60 agagcucugg cccccuuggc augucuuugg agccaugcag cuucccgucu gccaguucua 120 uccucaagca ccaggacacc a 141 <210> 281 <211> 78 <212> RNA <213> Homo sapiens <400> 281 auacuugagg agaaauuauc cuuggugugu ucgcuuuauu uaugaugaau cauacaagga 60 caauuucuuu uugaguau 78 <210> 282 <211> 23 <212> RNA <213> Homo sapiens <400> 282 ccugcagcga cuugauggcu ucc 23 <210> 283 <211> 20 <212> RNA <213> Homo sapiens <400> 283 aaaguagcug uaccauuugc 20 <210> 284 <211> 210 <212> RNA <213> Homo sapiens <400> 284 aagacuauac ucucaggaau cauuucuaua guuuuuuacu agagaaauuu cucugaacgu 60 guagagcacu ggaaaccgug aggagaagcu gccuucucuu cugagcauga agugagcucu 120 caguguugcu ucucugcaac ugccauuugc cauugaugau cguucuucuc uuccucuggg 180 agaguaaaag gguacaggau gcagucugag 210 <210> 285 <211> 94 <212> RNA <213> Homo sapiens <400> 285 uggaucgaug augacuuuaa aauggaucuc aucggaaucu gaacaaaaug agugaccaaa 60 ucacuucugu gccacuucug ugagcugagg ucca 94 <210> 286 <211> 21 <212> RNA <213> Homo sapiens <400> 286 ggacccaccc ggccgggaau a 21 <210> 287 <211> 23 <212> RNA <213> Homo sapiens <400> 287 uugaauucuu ggccuuaagu gau 23 <210> 288 <211> 18 <212> RNA <213> Homo sapiens <400> 288 ugagaugaca cuguagcu 18 <210> 289 <211> 22 <212> RNA <213> Homo sapiens <400> 289 uguaaacauc cccgacugga ag 22 <210> 290 <211> 101 <212> RNA <213> Homo sapiens <400> 290 gcgagaagau cucaugcugu gacucucugg agggaagcac uuucuguugu cugaaagaaa 60 acaaagcgcu ucucuuuaga guguuacggu uugagaaaag c 101 <210> 291 <211> 73 <212> RNA <213> Homo sapiens <400> 291 ugggcuuugc ccgcuuucug agcuggaccc ucucucuacc ucuggugcag aacuacagcg 60 gaaggaaucu cug 73 <210> 292 <211> 22 <212> RNA <213> Homo sapiens <400> 292 gagcuuauuc auaaaagugc ag 22 <210> 293 <211> 23 <212> RNA <213> Homo sapiens <400> 293 uguaaacauc cuacacucuc agc 23 <210> 294 <211> 71 <212> RNA <213> Homo sapiens <400> 294 uggaucaauc augacuacug guauuggaug ggucuucguc agugaaugcc uaucuggaac 60 ucugaggucc a 71 <210> 295 <211> 65 <212> RNA <213> Homo sapiens <400> 295 ugucugggga uuuggagaag uggugagcgc aggucuuugg caccaucucc ccuggucccu 60 uggcu 65 <210> 296 <211> 23 <212> RNA <213> Homo sapiens <400> 296 ucucugagua ccauaugccu ugu 23 <210> 297 <211> 22 <212> RNA <213> Homo sapiens <400> 297 uugagaauga ugaaucauua gg 22 <210> 298 <211> 22 <212> RNA <213> Homo sapiens <400> 298 guugggacaa gaggacgguc uu 22 <210> 299 <211> 20 <212> RNA <213> Homo sapiens <400> 299 ccugcguguu uucuguccaa 20 <210> 300 <211> 22 <212> RNA <213> Homo sapiens <400> 300 aacacaccug guuaaccucu uu 22 <210> 301 <211> 22 <212> RNA <213> Homo sapiens <400> 301 ugugacaaua gagaugaaca ug 22 <210> 302 <211> 82 <212> RNA <213> Homo sapiens <400> 302 cacaacugca uggcaucguc cccugguggc uguggccuag ggcaagccac aaagccacuc 60 agugaugaug ccagcaguug ug 82 <210> 303 <211> 22 <212> RNA <213> Homo sapiens <400> 303 ugcccugugg acucaguucu gg 22 <210> 304 <211> 127 <212> RNA <213> Homo sapiens <400> 304 uucuaaagug uugaguucag uccagggugg auccccugcu cuguuaauug aacuggaaca 60 uuuaaacugg cuaggcaaaa ugccuacaua gaaagcauua cucuuuauuc auccccagcc 120 uacaaaa 127 <210> 305 <211> 23 <212> RNA <213> Homo sapiens <400> 305 ggcaggaggg cugugccagg uug 23 <210> 306 <211> 23 <212> RNA <213> Homo sapiens <400> 306 uuaaugcuaa ucgugauagg ggu 23 <210> 307 <211> 21 <212> RNA <213> Homo sapiens <400> 307 ucccuucuuc cugggcccuc a 21 <210> 308 <211> 104 <212> RNA <213> Homo sapiens <400> 308 acucuuuugu aguucauaag ugugaugauu ugguguucau gugaacaugu gaaacgugcc 60 acccucaaac cuuguuacaa ugugggcaua uuacccaucu gaca 104 <210> 309 <211> 83 <212> RNA <213> Homo sapiens <400> 309 ucaggcugug acccucuuga gggaagcacu uucuguuguc ugaaagaaga gaaagugcuu 60 ccuuuuagag gcuuacuguc uga 83 <210> 310 <211> 22 <212> RNA <213> Homo sapiens <400> 310 cccugugccc ggcccacuuc ug 22 <210> 311 <211> 21 <212> RNA <213> Homo sapiens <400> 311 uagcagcaca gaaauauugg c 21 <210> 312 <211> 62 <212> RNA <213> Homo sapiens <400> 312 gagggagugg ggugggaccc agcuguuggc cauggcgaca acaccugggu uguccccucu 60 ag 62 <210> 313 <211> 22 <212> RNA <213> Homo sapiens <400> 313 cccaauacac ggucgaccuc uu 22 <210> 314 <211> 21 <212> RNA <213> Homo sapiens <400> 314 uaacgcauaa uauggacaug u 21 <210> 315 <211> 110 <212> RNA <213> Homo sapiens <400> 315 guguugggga cucgcgcgcu ggguccagug guucuuaaca guucaacagu ucuguagcgc 60 aauugugaaa uguuuaggac cacuagaccc ggcgggcgcg gcgacagcga 110 <210> 316 <211> 22 <212> RNA <213> Homo sapiens <400> 316 cuccuggggc ccgcacucuc gc 22 <210> 317 <211> 22 <212> RNA <213> Homo sapiens <400> 317 uggggaggug uggagucagc au 22 <210> 318 <211> 21 <212> RNA <213> Homo sapiens <400> 318 caucccuugc augguggagg g 21 <210> 319 <211> 83 <212> RNA <213> Homo sapiens <400> 319 acaggaacac uggacuuggu gucagauggg augagcccug gcucuguuuc cuagcagcaa 60 ucugaucuug agcuagucac ugg 83 <210> 320 <211> 134 <212> RNA <213> Homo sapiens <400> 320 ugccucugac cuggguagag uggcaucugg cugugacauu caucucauau cagccaggga 60 caaagcaacc ccuuguuuau uucagcuugg ccuuuugucu gugcccaugc cugguucaug 120 ccuuggacac acua 134 <210> 321 <211> 119 <212> RNA <213> Homo sapiens <400> 321 uucuuauuga gcuccuuucu gucuacuggu ggcagucuau ggauuugcac aagacaaaac 60 uagcgcuauu uuaccuucug ucuuuaaaca gguauauuug acuguuuugu gagaaauuc 119 <210> 322 <211> 95 <212> RNA <213> Homo sapiens <400> 322 aaagacaugc uguccacagu guguuugaua agcugacaug ggacagggau ucuuuucacu 60 guugugucag uuuaucaaac ccauacuugg augac 95 <210> 323 <211> 20 <212> RNA <213> Homo sapiens <400> 323 ucccacuacu ucacuuguga 20 <210> 324 <211> 18 <212> RNA <213> Homo sapiens <400> 324 ccgcuuucug agcuggac 18 <210> 325 <211> 23 <212> RNA <213> Homo sapiens <400> 325 cugauaagaa cagaggccca gau 23 <210> 326 <211> 81 <212> RNA <213> Homo sapiens <400> 326 agccuuuagc aaguuguaau cuuuuugcug auggaggguc uugccuccau ggggauggcu 60 gaugaugaug gugcugaagg c 81 <210> 327 <211> 110 <212> RNA <213> Homo sapiens <400> 327 ugcccaguga ugacaccauc cuugcucccc gugcccccca ggggcuaugg gcgacaccau 60 ggcugccccu gggcugggcc aguggggcca augcccaggg gcugagggca 110 <210> 328 <211> 53 <212> RNA <213> Homo sapiens <400> 328 gccuucucuu cccaguucuu ccuggagucg gggaaaagcu ggguugagaa ggu 53 <210> 329 <211> 102 <212> RNA <213> Homo sapiens <400> 329 acccuucuua guucauaagc augaugauug gguuuucaua cucaugugug agaugugucu 60 cucucaaacu uugugaaaag ucagcacaug acccaucuga ug 102 <210> 330 <211> 142 <212> RNA <213> Homo sapiens <400> 330 caccuaaugu gugccaagau cuguucauuu augaucucac cgaguccugu gagguuggca 60 uuguugucug gcauugucug auauacaaca gugccaaccu cacaggacuc agugagguga 120 aacugaggau uaggaaggug ua 142 <210> 331 <211> 87 <212> RNA <213> Homo sapiens <400> 331 ucucagccug ugacccucua gagggaagcg cuuucuguug ucugaaagaa aagaaagugc 60 aucuuuuuag aggauuacag uuugaga 87 <210> 332 <211> 134 <212> RNA <213> Homo sapiens <400> 332 uguucugaca ugggaagagu agcuucuggu ugguggagcc caucucacau uagccagaga 60 caaagcaaca ccuuguuuau cccggcuugg cuuuuggccu guguccauga cugguccaua 120 ccuuggacac augg 134 <210> 333 <211> 96 <212> RNA <213> Homo sapiens <400> 333 auccuuuugu gggucauaug caugaugauu ggguguucac gcacaaguau gagaugugcc 60 accuuuuuac agcauuggca cauuaccugu cugaug 96 <210> 334 <211> 22 <212> RNA <213> Homo sapiens <400> 334 gcgacucuga aaacuagaag gu 22 <210> 335 <211> 104 <212> RNA <213> Homo sapiens <400> 335 aucuuuuugu gguucauaag caugaugauu ggguuuucau accauugugu aagaugugcc 60 uuucucagac cuugccaaaa cacuggcaca uuaccugucu gaua 104 <210> 336 <211> 88 <212> RNA <213> Homo sapiens <400> 336 ucucaggcug ugacccucua gagggaagcg cuuucuguug gcuaaaagaa aagaaagcgc 60 uucccuucag aguguuaacg cuuugaga 88 <210> 337 <211> 78 <212> RNA <213> Homo sapiens <400> 337 uggaccaaug augaugacug gugguguaug aguuaaaggu gaugaauagu aagugucuuu 60 guuaguggca aguucaga 78 <210> 338 <211> 97 <212> RNA <213> Homo sapiens <400> 338 caaguuggca cuguagaaua uugaggaaaa gauggucuua uugcaaagau uuucaauaag 60 accauccuuu ccucaauauu cugugguguc aucuuug 97 <210> 339 <211> 22 <212> RNA <213> Homo sapiens <400> 339 cugggguucu gagacagaca gu 22 <210> 340 <211> 22 <212> RNA <213> Homo sapiens <400> 340 aacccguaga uccgaucuug ug 22 <210> 341 <211> 21 <212> RNA <213> Homo sapiens <400> 341 uaugugaccu cggaugaauc a 21 <210> 342 <211> 21 <212> RNA <273> Homo sapiens <400> 342 gaaggcgcuu cccuuuggag u 21 <210> 343 <211> 22 <212> RNA <213> Homo sapiens <400> 343 caauguuucc acagugcauc ac 22 <210> 344 <211> 62 <212> RNA <213> Homo sapiens <400> 344 gccucccuuc acuuccuggc cauccaggca ucugugucug uguccgggaa guggaggagg 60 gc 62 <210> 345 <211> 88 <212> RNA <213> Homo sapiens <400> 345 acuuccuggu auuugaagau gcgguugacc auggugugua cgcuuuauuu gugacguagg 60 acacaugguc uacuucuucu caauauca 88 <210> 346 <211> 72 <212> RNA <213> Homo sapiens <400> 346 uggaucaaug augacaaagu aucaugaaug agggauugug aauaaucuau uuuuaugaac 60 cuguggucaa au 72 <210> 347 <211> 107 <212> RNA <213> Homo sapiens <400> 347 auccuuuugu gguucauaag caugaugauu agauuuucau gcuauugggu gagauaugcc 60 uuccucagac uuuguuacag cauaggcaca uuacaaccug ucugaua 107 <210> 348 <211> 59 <212> RNA <213> Homo sapiens <400> 348 guccaggcag gagccggacu ggaccucagg gaagaggcug acccggcccc ucuugcggc 59 <210> 349 <211> 76 <212> RNA <213> Homo sapiens <400> 349 aagccuggca uauuugguau aacuuaagca ccagguaaaa ucuggugcuu aaguuguacc 60 aaguauagcc aaguuu 76 <210> 350 <211> 219 <212> RNA <213> Homo sapiens <400> 350 aaggcuauac uuucagggau cauuuuuaua gcuuauuacu agaggaguua augugaaugu 60 guagagcacc agaaaccuug aggaggaggu gcagcguucu cuccugagca uaaagcuggc 120 ccgcaguauu guguugccuc acugcaacug ccauuugcca uugaugauga uuguucucuu 180 ucacugagag aguaagagga caggaugcau ucuaacugg 219 <210> 351 <211> 21 <212> RNA <213> Homo sapiens <400> 351 agguugucug ugaugaguuc g 21 <210> 352 <211> 23 <212> RNA <213> Homo sapiens <400> 352 uucaugaacu gggucuagcu ugg 23 <210> 353 <211> 23 <212> RNA <213> Homo sapiens <400> 353 uagcccccag gcuucacuug gcg 23 <210> 354 <211> 103 <212> RNA <213> Homo sapiens <400> 354 auccuuuugu aguucauaag gaugaugacu gaguguucac acucgugugu gagaugugcc 60 acccucagac cuugaaaucu ucagucacuc uuguuaagug aac 103 <210> 355 <211> 20 <212> RNA <213> Homo sapiens <400> 355 ggcuccuugg ucuaggggua 20 <210> 356 <211> 18 <212> RNA <213> Homo sapiens <400> 356 gaaggaccug caccuucg 18 <210> 357 <211> 22 <212> RNA <213> Homo sapiens <400> 357 cuuucagucg gauguuuaca gc 22 <210> 358 <211> 85 <212> RNA <213> Homo sapiens <400> 358 cucaagcugu gacucuccag agggaugcac uuucucuuau gugaaaaaaa agaaggcgcu 60 ucccuuuaga gcguuacggu uuggg 85 <210> 359 <211> 20 <212> RNA <213> Homo sapiens <400> 359 gugcaaaagu caucacgguu 20 <210> 360 <211> 22 <212> RNA <213> Homo sapiens <400> 360 acuaaaggau auagaagguu uu 22 <210> 361 <211> 21 <212> RNA <213> Homo sapiens <400> 361 aggcccuguc cucugcccca g 21 <210> 362 <211> 23 <212> RNA <213> Homo sapiens <400> 362 uagcagcggg aacaguucug cag 23 <210> 363 <211> 66 <212> RNA <213> Homo sapiens <400> 363 cugcgaugau ggcauuucuu aggacaccuu uggauuaaua augaaaacaa cuacucucug 60 agcagc 66 <210> 364 <211> 24 <212> RNA <213> Homo sapiens <400> 364 uguaggaaca guugaauuuu ggcu 24 <210> 365 <211> 216 <212> RNA <213> Homo sapiens <400> 365 aagacugugc uuucagggau caugucuaua guuugccacu agagaaguuu uuuugaacau 60 guaguagggc accagaagca caaggaagag gcacagccuu cucuccugag caugaaucug 120 gcucuugguc uugcuuuguu ccagcuacca uuugccauug auuauguccu ucucuuccuu 180 ccagaaagua aaagggagag aaugcagucu gagugg 216 <210> 366 <211> 93 <212> RNA <213> Homo sapiens <400> 366 auccuuuugu aguucauaag cugaugguug gguuuucacg cucaugugug agauguguuc 60 cuucauaucu gucaacacac uaccgggcug uug 93 <210> 367 <211> 24 <212> RNA <213> Homo sapiens <400> 367 uugaagggac aagucagaua ugcc 24 <210> 368 <211> 18 <212> RNA <213> Homo sapiens <400> 368 auggucaccu ccgggacu 18 <210> 369 <211> 22 <212> RNA <213> Homo sapiens <400> 369 ggaggaaccu uggagcuucg gc 22 <210> 370 <211> 22 <212> RNA <213> Homo sapiens <400> 370 agcuguaauu agucaguuuu cu 22 <210> 371 <211> 110 <212> RNA <213> Homo sapiens <400> 371 gagcugcuug ccuccccccg uuuuuggcaa ugguagaacu cacacuggug agguaacagg 60 auccgguggu ucuagacuug ccaacuaugg ggcgaggacu cagccggcac 110 <210> 372 <211> 121 <212> RNA <213> Homo sapiens <400> 372 caaaguucug gaauuacagg ugugagccac cgugcccagc auuuaaaauu uuaauaugua 60 cuuuuugcaa cccagaacuc auuguucagu augaguuuug auacauauaa gaagggauau 120 u 121 <210> 373 <211> 22 <212> RNA <213> Homo sapiens <400> 373 aaaaacugag acuacuuuug ca 22 <210> 374 <211> 22 <212> RNA <213> Homo sapiens <400> 374 ugauggagcu gggaauacuc ug 22 <210> 375 <211> 21 <212> RNA <213> Homo sapiens <400> 375 acucggcugc gguggacaag u 21 <210> 376 <211> 82 <212> RNA <213> Homo sapiens <400> 376 aaggagcacu cacuccaauu ucccuggacu gggggcaggc ugccaccucc uggggacagg 60 ggauuggggc aggauguucc ag 82 <210> 377 <211> 102 <212> RNA <213> Homo sapiens <400> 377 auccuuuugu aguuuauaag caugaugaug ggugcucaca cucaucugag augugucucc 60 cucuaagccu uguaacaaca ucagcacguu acccuucuga ug 102 <210> 378 <211> 19 <212> RNA <213> Homo sapiens <400> 378 guggucucuu ggcccccag 19 <210> 379 <211> 112 <212> RNA <213> Homo sapiens <400> 379 aguuuaaaaa auuuguuaag caugaugauu aacuuuucac aauaaugcaa uaauguguga 60 gcuaugccuc ucucaaaccu uauuaugaug uuggcccauu acccaucuga ug 112 <210> 380 <211> 23 <212> RNA <213> Homo sapiens <400> 380 ggguuuguag cuuugcuggc aug 23 <210> 381 <211> 59 <212> RNA <213> Homo sapiens <400> 381 aaacuaauau acccauauuc uggcuaggug aucaucagaa uauggguaua uuaguuugg 59 <210> 382 <211> 81 <212> RNA <213> Homo sapiens <400> 382 gccuguguga ugauggagcu gggaauacuc uggggagaga guccucuuuu cagcuguauu 60 uugcuuccuu cccacacaga c 81 <210> 383 <211> 22 <212> RNA <213> Homo sapiens <400> 383 uugcuaagua ggcugagauu ga 22 <210> 384 <211> 22 <212> RNA <213> Homo sapiens <400> 384 aaaaguaauu gugguuuuug cc 22 <210> 385 <211> 85 <212> RNA <213> Homo sapiens <400> 385 uuaaaugaug auuuuuuuaa acaaauguau cagagugcau ucauucaaag gaauguuguc 60 uucuggcaag uaaaaaucca ugcag 85 <210> 386 <211> 84 <212> RNA <213> Homo sapiens <400> 386 uuuugguuga aauaugauga guguacaaaa ucuugauuua agugaaugaa aaauuacaag 60 auccaacucu gauuucagcc agag 84 <210> 387 <211> 104 <212> RNA <213> Homo sapiens <400> 387 auccuuuugu aguucaugag uguaaugauu gaguguucau gcacaugugu gagauaugcc 60 acccuugaac cuuguuacac cguugucaca uugcccguuu gaca 104 <210> 388 <211> 131 <212> RNA <213> Homo sapiens <400> 388 aggcaggauc uaguuacauu guagcuguga agugcugcau ugucuuugcc cccugcucaa 60 aauaaaacug uuaccuuuca agcccugucu gccauggugc uguagcagca gggauguuug 120 gucucauaca u 131 <210> 389 <211> 22 <212> RNA <213> Homo sapiens <400> 389 cuauacaacu uacuacuuuc cc 22 <210> 390 <211> 22 <212> RNA <213> Homo sapiens <400> 390 guagcaccuu gcaggauaag gu 22 <210> 391 <211> 61 <212> RNA <213> Homo sapiens <400> 391 uccgcucugu ggaguggggu gccugucccc ugccacuggg ugacccaccc cucuccacca 60 g 61 <210> 392 <211> 134 <212> RNA <213> Homo sapiens <400> 392 uuggcccuua ucgaagcugc agcugcuucc gcauagcugc uguggucaaa aaggagccca 60 gagugacagu uuuccuugac ggucgccguu cuguuuguug uaacugaucu gcaacauuuu 120 gggaaaauac aguu 134 <210> 393 <211> 22 <212> RNA <213> Homo sapiens <400> 393 ugugacuggu ugaccagagg gg 22 <210> 394 <211> 22 <212> RNA <213>智人 <400> 394 caagggacca agcauucauu au 22 <210> 395 <211> 22 <212> RNA <213>智人 <400> 395 ucccaagggu gagaugcugc ca 22 <210> 396 <211> 82 <212> RNA <213>智人 <400> 396 ugguacucgg agggagguug uccgugguga guucgcauua uuuaaugaug cccaauacac 60 ggucgaccuc uuuucgguau ca 82 <210> 397 <211> 55 <212> RNA <213>智人 <400> 397 ccacugcugg ccggggcccc uacucaaggc uaggaggccu uggccaagga caguc 55 <210> 398 <211> 22 <212> RNA <213>智人 <400> 398 cuucugauca agauuugugg ug 22 <210> 399 <211> 111 <212> RNA <213>智人 <400> 399 aagcuuauga ugacguaagu gugacgacau uggguuuuca cguucaugug ugagaugugc 60 cucccucaag ccuuauuaca augccaguac auuuuuuuuc cacaucugau g 111 <210> 400 <211> 85 <212> RNA <213> Homo sapiens <400> 400 ucaggcaaag ggauauuuac agauacuuuu uaaaauuugu uugaguugag gcagauuaaa 60 uaucuguauu cuccuuugcc ugcag 85 <210> 401 <211> 21 <212> RNA <213> Homo sapiens <400> 401 cggcgcccgu gucuccucca g 21 <210> 402 <211> 22 <212> RNA <213> Homo sapiens <400> 402 augaagccuu cucugccuua cg 22 <210> 403 <211> 21 <212> RNA <213> Homo sapiens <400> 403 aaaaguaauu gcaguuuuug c 21 <210> 404 <211> 104 <212> RNA <213> Homo sapiens <400> 404 aucuuuucgu aguucauaag ugugaugacu ggguauucau gcauguaugu gggauaugcc 60 acccuugacc cuuguuacaa cauuagcaca uuaaccaucu gaca 104 <210> 405 <211> 69 <212> RNA <213> Homo sapiens <400> 405 uggagggcug cgggacugua gagggcauga gcucaggagc ucaggccagc ucauggugca 60 aggccucug 69 <210> 406 <211> 74 <212> RNA <213> Homo sapiens <400> 406 uggaccagug auggugacug guggugugug agucaugcac agugaauauc augugucugg 60 aacucugagg ucca 74 <210> 407 <211> 22 <212> RNA <213> Homo sapiens <400> 407 auagcagcau gaaccugucu ca 22 <210> 408 <211> 21 <212> RNA <213> Homo sapiens <400> 408 aaaauuucuu ucacuacuua g 21 <210> 409 <211> 63 <212> RNA <213> Homo sapiens <400> 409 uggcgaugag gagguaccua uugugogag uaacggugau aauuuuauac gcuauucuga 60 gcc 63 <210> 410 <211> 77 <212> RNA <213>智人 <400> 410 cacggccaug agcaucauccc 60 caugcaccgc ucugaga 77 <210> 411 <211> 78 <212> RNA <213>智人 <400> 411 ggcaccauua gguagacugg gauuuguu ugagcgcagu agacaaaaaaaacacu 60 shake auggggcc 78 <210> 412 <211> 90 <212> RNA <213>智人 <400> 412 squeal squeak squeak gasp squeak squeak squeak aaaaaaaaaaagg 60 90 <210> 413 <211> 105 <212> RNA <213>智人 <400> 413 aauugucagc aggcaauuau cugaggaugc aggagaggaa gggggcuucu uuuugacgcc 60 uacuucauca gcugcuccuc agaucagagc cuugcagguc aggcc 105 <210> 414 <211> 142 <212> RNA <213> Homo sapiens <400> 414 uugcccgaug auuauaaaaa gacgcguuau uaagaggacu uuaugcugga guucuugacg 60 uuuuucucuc uuuucuauac uucuuuuucu uucuuugaau guccagcguc cugugagcga 120 agauuaugag auaugagggc aa 142 <210> 415 <211> 96 <212> RNA <213> Homo sapiens <400> 415 gugacccugg gcaaguuccu gaagaucaga cacaucagau cccuuaucug uaaaaugggc 60 augauccagg aaccugccuc uacgguugcc uugggg 96 <210> 416 <211> 22 <212> RNA <213> Homo sapiens <400> 416 uagcaccauc ugaaaucggu ua 22 <210> 417 <211> 80 <212> RNA <213> Homo sapiens <400> 417 gguuggcuau aacuaucauu uccaagguug ugcuuuuagg aaauguuggc uguccugcgg 60 agagagaaug gggagccagg 80 <210> 418 <211> 73 <212> RNA <213> Homo sapiens <400> 418 cucugccucc cgugccuacu gagcugaaac acaguugguu uguguacacu ggcucaguuc 60 agcaggaaca ggg 73 <210> 419 <211> 21 <212> RNA <213> Homo sapiens <400> 419 ucgugucccu cuuguccaca g 21 <210> 420 <211> 85 <212> RNA <213> Homo sapiens <400> 420 gugaggacuc gggaggugga ggguggugcc gccggggccg ggcgcuguuu cagcucgcuu 60 cuccccccac cuccucucuc cucag 85 <210> 421 <211> 22 <212> RNA <213> Homo sapiens <400> 421 ucucagcugc ugcccucucc ag 22 <210> 422 <211> 23 <212> RNA <213> Homo sapiens <400> 422 acuucaccug guccacuagc cgu 23 <210> 423 <211> 17 <212> RNA <213> Homo sapiens <400> 423 cagccugaca ggaacag 17 <210> 424 <211> 96 <212> RNA <213> Homo sapiens <400> 424 ugggggagug aagaguagau aaaauauugg uaccugauga aucugaggcc agguuucaau 60 acuuuaucug cucuucauuu ccccauaucu acuuac 96 <210> 425 <211> 103 <212> RNA <213> Homo sapiens <400> 425 auucuuuagu aguucauaau gcuaugauug gguuuccaug ugcacaugua agaugugccu 60 cucucaagcc uuguugugac aucagcacau uacccaucug aug 103 <210> 426 <211> 129 <212> RNA <213> Homo sapiens <400> 426 cucauaccua aacccaagaa ucacuuucuu auagugauga uuuaaacaga ugcaaacagc 60 gagcacaucu ugucaccuuu gcgggacugu ggcugugccc cucgcaguaa auuuggaggu 120 ucuacaucc 129 <210> 427 <211> 74 <212> RNA <213> Homo sapiens <400> 427 uauauauaga gauguaugga aucuguauau aucuauauau auguguauau auagauucca 60 uaaaucuaua uaug 74 <210> 428 <211> 71 <212> RNA <213> Homo sapiens <400> 428 uggaacaaug augagagugu gucaugaacc aagguuauga uuaaucuagu ucugugcauc 60 ugaaauccgu u 71 <210> 429 <211> 17 <212> RNA <213> Homo sapiens <400> 429 ggugaggcua gcuggug 17 <210> 430 <211> 67 <212> RNA <213> Homo sapiens <400> 430 agagauggua gacuauggaa cguaggcguu augauuucug accuauguaa caugguccac 60 uaacucu 67 <210> 431 <211> 101 <212> RNA <213> Homo sapiens <400> 431 auccuuuagu ucuuaaacau gacaauugga uguuuaugca uaugugugag augugucacc 60 cuugaaccuu guuaccaugu cugcacauua ccuaucugac a 101 <210> 432 <211> 77 <212> RNA <213> Homo sapiens <400> 432 ugauagggaa accaggcaag aaauauuguc uccucaaguu gcgacgagac aguaguucuu 60 gccugguuuc ucuauca 77 <210> 433 <211> 23 <212> RNA <213> Homo sapiens <400> 433 acaaaguaca gcauuagccu uag 23 <210> 434 <211> 84 <212> RNA <213> Homo sapiens <400> 434 ccagucacgu ccccuuauca cuuuuccagc ccagcuuugu gacuguaagu guuggacgga 60 gaacugauaa ggguagguga uuga 84 <210> 435 <211> 125 <212> RNA <213> Homo sapiens <400> 435 acagacucac uuugcaccug gcugcagccu caugggggug cuuuuuccau gugccaggga 60 aacauucugg gguguugugg cugccugacc uaucaagggu gaugcagcug ucuggggaua 120 cagga 125 <210> 436 <211> 131 <212> RNA <213> Homo sapiens <400> 436 ggcuugcugg ugcuuaccac aggcugaauu cuuacacuga cuauauagaa aaggagguag 60 aguaaaccua cccaauauac cccucagccc aggcucugug ccugaucuau auugugaaug 120 ugggaacaua g 131 <210> 437 <211> 132 <212> RNA <213> Homo sapiens <400> 437 cuucccauuu auuugcugcu uguagucuca cagugauacg agcaguuaua cgcaugggau 60 aaaauaacau ugggccacug uaaauugaga ugaaguaacc auuuucaucu cuucugcagg 120 gacuagacau ug 132 <210> 438 <211> 97 <212> RNA <213> Homo sapiens <400> 438 ucuuccucuc uguccucugg aauuugguuu cugaggcacu uaguagguga uagcaugacu 60 gacugccuca cugaccacuu ccagaugagg guuacuc 97 <210> 439 <211> 97 <212> RNA <213> Homo sapiens <400> 439 ggccuagcca aauacuguau uuuugaucga cauuugguug aaaaauaucu auguauuagu 60 aaaccugugu uguucaagag uccacugugu uuugcug 97 <210> 440 <211> 69 <212> RNA <213> Homo sapiens <400> 440 ccaccacuua aacguggaug uacuugcuuu gaaacuaaag aaguaagugc uuccauguuu 60 uggugaugg 69 <210> 441 <211> 201 <212> RNA <213> Homo sapiens <400> 441 uccagcagua gucagcuguc uggacagaac cauuccuggg aucauguuac acugcuggga 60 gaagaauguc uucucuucau ccaguugcgu ccaucacugu ucugguggug ucuggcacug 120 gugcaaggca gaacugugcu uccuugagag ugugcugagc auucaccuug gcugcuuggu 180 ucuagucuag gagcagacac a 201 <210> 442 <211> 22 <212> RNA <213> Homo sapiens <400> 442 uuuguucguu cggcucgcgu ga 22 <210> 443 <211> 94 <212> RNA <213> Homo sapiens <400> 443 gaauccgguc cguacaaacu cugcuguguu gaaugauugg ugaguuuguu ugcucauuga 60 uugaaucacu gcagaguuug uacggaccgg auuc 94 <210> 444 <211> 82 <212> RNA <213> Homo sapiens <400> 444 guguugauga ugagaaccuu auauuauccu gaagagaggu gaugacuuaa aaaucaugcu 60 caauaggauu acgcugaggc cc 82 <210> 445 <211> 22 <212> RNA <213> Homo sapiens <400> 445 cucuagaggg aagcacuuuc uc 22 <210> 446 <211> 81 <212> RNA <213> Homo sapiens <400> 446 guuccacucu agcagcacgu aaauauuggc guagugaaau auauauuaaa caccaauauu 60 acugugcugc uuuaguguga c 81 <210> 447 <211> 90 <212> RNA <213> Homo sapiens <400> 447 uugaggcacu ggguagugga ugauggagac ucgguaccca cugcugaggg uggggaccaa 60 gucugcguca uccucuccuc agugccucaa 90 <210> 448 <211> 20 <212> RNA <213> Homo sapiens <400> 448 aggcauggga ggucagguga 20 <210> 449 <211> 100 <212> RNA <213> Homo sapiens <400> 449 cagagucucc uucguguaca gggaggagac uguacgugag agauagucag auccgcaugu 60 uagagcagag ucuccuucgu guacagggag gagauuguac 100 <210> 450 <211> 21 <212> RNA <213> Homo sapiens <400> 450 auugaaaccu cuaagagugg a 21 <210> 451 <211> 115 <212> RNA <213> Homo sapiens <400> 451 ucuguuuauc accagauccu agaacccuau caauauuguc ucugcugugu aaauaguucu 60 gaguagugca auauugcuua uaggguuuug guguuuggaa agaacaaugg gcagg 115 <210> 452 <211> 22 <212> RNA <213> Homo sapiens <400> 452 cuuggcaccu agcaagcacu ca 22 <210> 453 <211> 129 <212> RNA <213> Homo sapiens <400> 453 acuggaggac uaagaaggcu gagucugaug aaguaagacu uugcugauac auuccuccua 60 gaaaaaaggg uuggagagag cagccuucac ugaagaguau cacagggcug acuguacuac 120 ccaacacuc 129 <210> 454 <211> 72 <212> RNA <213> Homo sapiens <400> 454 uuggguaagu gcuuccaugc uucaguuucc uuacugguaa gauggaugua guaauagcac 60 cuaccuuaua ga 72 <210> 455 <211> 21 <212> RNA <213> Homo sapiens <400> 455 cgaccucggc gaccccucac u 21 <210> 456 <211> 87 <212> RNA <213> Homo sapiens <400> 456 ugguuggguu uggauuguug uacuuuuuuu uuuguucguu gcauuuuuag gaacaaaaaa 60 aaaagcccaa cccuucacac cacuuca 87 <210> 457 <211> 72 <212> RNA <213> Homo sapiens <400> 457 uggaggugau gaacugucug agccugaccu uguagaaugg aggcaaaaaa acugauuuaa 60 ugagccugau cc 72 <210> 458 <211> 22 <212> RNA <213> Homo sapiens <400> 458 caugcuagga uagaaagaau gg 22 <210> 459 <211> 22 <212> RNA <213> Homo sapiens <400> 459 cucaguagcc aguguagauc cu 22 <210> 460 <211> 150 <212> RNA <213> Homo sapiens <400> 460 ugcccggccu cccauuaaau ugguuuuuca gacaaaucac aaauuuguuu agguauaagu 60 auaucccaug uaaucuuugg gacauacuua ugcuaaaaua auuguuccuu guugauugga 120 aauuuuaauu uuaauuaggu guccuguauu 150 <210> 461 <211> 21 <212> RNA <213> Homo sapiens <400> 461 ugcguuucuc cucuugagca g 21 <210> 462 <211> 133 <212> RNA <213> Homo sapiens <400> 462 gcauggccga auacuguguu uuuaucagua guuuacacag ccagacacca ugcaaaagca 60 gucuucccuu uagaaugacu gaugguaugc uaagguuuuu cauagcauau cauuauuaaa 120 ggugaauaca aau 133 <210> 463 <211> 24 <212> RNA <213> Homo sapiens <400> 463 aacaacaaaa ucacuagucu ucca 24 <210> 464 <211> 82 <212> RNA <213> Homo sapiens <400> 464 ccugccgggg cuaaagugcu gacagugcag auaguggucc ucuccgugcu accgcacugu 60 ggguacuugc ugcuccagca gg 82 <210> 465 <211> 82 <212> RNA <213> Homo sapiens <400> 465 gggucaauga ugagaaucuu auauuguccu gaagagaggu gaugacuuaa aaaucaugcu 60 caauaggauu acgcugaggc cc 82 <210> 466 <211> 21 <212> RNA <213> Homo sapiens <400> 466 uaauuuuaug uauaagcuag u 21 <210> 467 <211> 135 <212> RNA <213> Homo sapiens <400> 467 gcauggguuu ggauuuauga ugggcuggau ucccuaggcc ucucauagua ccccaugcca 60 gagcaaacug uagccccaac cauugccggg ccucuaugcc uguaggcugc uggcacugaa 120 guggguugca cagua 135 <210> 468 <211> 22 <212> RNA <213> Homo sapiens <400> 468 accuuccucu ccaugggucu uu 22 <210> 469 <211> 148 <212> RNA <213> Homo sapiens <400> 469 cuucgaugaa gagaugauga cgagucugac uuggggaugu ucucuuugcc cagguggccu 60 acucugugcu gcguucugug gcacaguuua aagagcccug guugaaguaa uuuccuaaag 120 augacuuaga ggcauuuguc ugagaagg 148 <210> 470 <211> 21 <212> RNA <213> Homo sapiens <400> 470 ugugucccau uauuggugau u 21 <210> 471 <211> 90 <212> RNA <213> Homo sapiens <400> 471 ugcccuucgc gaaucuuuuu gcggucuggg cuugcuguac auaacucaau agccggaagc 60 ccuuacccca aaaagcauuu gcggagggcg 90 <210> 472 <211> 22 <212> RNA <213> Homo sapiens <400> 472 aggacuggac ucccggcagc cc 22 <210> 473 <211> 23 <212> RNA <213> Homo sapiens <400> 473 uguaguguuu ccuacuuuau gga 23 <210> 474 <211> 65 <212> RNA <213> Homo sapiens <400> 474 gagggcuagg uggggggcuu gaagccccga gaugccucac gucuucaccc cucucaccua 60 agcag 65 <210> 475 <211> 23 <212> RNA <213> Homo sapiens <400> 475 acuugggcac ugaaacaaug ucc 23 <210> 476 <211> 22 <212> RNA <213> Homo sapiens <400> 476 aucauaugaa ccaaacucua au 22 <210> 477 <211> 64 <212> RNA <213> Homo sapiens <400> 477 ugaugagggg guagaaagug gcugaagcga gauguuuguc uaaaagcacu uuucugucuc 60 ccag 64 <210> 478 <211> 72 <212> RNA <213> Homo sapiens <400> 478 ccuggugaug acagacgaca uugucagcca auccccaugu gguagugagg acauguccug 60 caguucugaa gg 72 <210> 479 <211> 72 <212> RNA <213> Homo sapiens <400> 479 agauucagcu uucccuucag agccuggcuu uggcaucuau gaaagccagg cucugaaggg 60 aaaguugaau cu 72 <210> 480 <211> 104 <212> RNA <213> Homo sapiens <400> 480 aucauuuugc agcuuauaca ugugaugacu ggguuuuuua acucauaagu gagaugugcc 60 uuucuuacau cuuauuauga cauuaguaca uuacccauuu gaua 104 <210> 481 <211> 91 <212> RNA <213> Homo sapiens <400> 481 auccuucugu aguuuaugag ugugaugauu ggcuguucau gugcauguau gagaugugcc 60 acccuugaac cuugucaugu cugaugugaa a 91 <210> 482 <211> 19 <212> RNA <213> Homo sapiens <400> 482 ucucccuuga gggcacuuu 19 <210> 483 <211> 74 <212> RNA <213> Homo sapiens <400> 483 uagaccagug augagaaucu gucaugaacc aaggaguauu auuaaucuaa uucuguuuac 60 cugagaguuu uaaa 74 <210> 484 <211> 86 <212> RNA <213> Homo sapiens <400> 484 aagagccaau gauguuuuua uucaaaaugu cugaaccugu cugaagcauc ccagugaugc 60 aacuucugug ugauacugag gcuuuu 86 <210> 485 <211> 100 <212> RNA <213> Homo sapiens <400> 485 auccuuuugu gguucauaag caugaugauu ggguuuccac auucuuguga gaugggccuc 60 ccuccaaccu uguuaugaug ucagcacauu acccuugacg 100 <210> 486 <211> 74 <212> RNA <213> Homo sapiens <400> 486 augauuauau gagggacaga ugccagaagc acugguuaug auuugcaucu ggcauccguc 60 acacagauaa uuau 74 <210> 487 <211> 22 <212> RNA <213> Homo sapiens <400> 487 aggugcucca ggcuggcuca ca 22 <210> 488 <211> 22 <212> RNA <213> Homo sapiens <400> 488 ucacaaaucu auaauaugca gg 22 <210> 489 <211> 100 <212> RNA <213> Homo sapiens <400> 489 ucccaucugg acccugcugg gcagggcuuc ugagcuccuu agcacuagca ggaggggcuc 60 caggggcccu cccuccaugg cagccaggac aggacucuca 100 <210> 490 <211> 74 <212> RNA <213> Homo sapiens <400> 490 uggaccaaug augacaacug ccggcguaug aguguugggu gaugaauaau acgugucuag 60 aacucugagg ucca 74 <210> 491 <211> 77 <212> RNA <213> Homo sapiens <400> 491 uuccagcccg aggccucugu gacgucacgg ugucugcggg aggagaccau gacgucacag 60 aggcuucgcg cucugag 77 <210> 492 <211> 87 <212> RNA <213> Homo sapiens <400> 492 ggucgcauuu cuccuucuua ccagcgcguu uucaguuuca uagggaagcc uuuccaugaa 60 acuggagcgc cuggaggaga aggggcc 87 <210> 493 <211> 23 <212> RNA <213> Homo sapiens <400> 493 ugacccccau gucgccucug uag 23 <210> 494 <211> 62 <212> RNA <213> Homo sapiens <400> 494 aaaaguacuu gcggauuugc caucaccuuu accuuuaaug gcaaaacugc aguuacuuuu 60 gc 62 <210> 495 <211> 76 <212> RNA <213> Homo sapiens <400> 495 ggucgcuuaa aucccaaugc uagacccggu ggcaaucaag gucuagccac caggucuagc 60 auugggauuu aagccc 76 <210> 496 <211> 79 <212> RNA <213> Homo sapiens <400> 496 auuaauaugg aagggagaag agcuuuaaug cucugaaaau gacuccaauc auuaaagcuc 60 uucucccuuc cauauuaau 79 <210> 497 <211> 69 <212> RNA <213> Homo sapiens <400> 497 ugcacugaug acagugaacc auaaaccaag aauuaugauu uauccaguuc uaugaaucuu 60 aaguccauu 69 <210> 498 <211> 110 <212> RNA <213> Homo sapiens <400> 498 auccuuuugu aguucauaag cgugaugacu gugguuucau gcuugugugu gagagauggg 60 ugggccuccc ucaaaccuug uuacgacgua ggcccauuac ccaucugaca 110 <210> 499 <211> 205 <212> RNA <213> Homo sapiens <400> 499 ccaaugugua auauccuggg auaucauuuu uucuaggcuu uguccacaug gcuuagggga 60 gcauagggcu cugccccaug auguacaguc ccuuuccuca guguuggaga ugaagcuggg 120 ucugguguuu gcacuuucau auuccuguag cuucucagaa uccuguggac agugacuggg 180 gagacaaacc augcaggaaa uaugu 205 <210> 500 <211> 103 <212> RNA <213> Homo sapiens <400> 500 auccuucuau auaguucaua agcuugauga ucgguguuca cacacaugug agauacgcca 60 ccugugaacc uuguuaggac aucagcacau uacccaucug aca 103 <210> 501 <211> 104 <212> RNA <213> Homo sapiens <400> 501 auccuuuugu aguucauaag cacaaugauu gaauuuucau gcucaugugu gagauaugcc 60 ucacuccagu cuuguuacag uguuagcaca uuaccuaucu gaua 104 <210> 502 <211> 77 <212> RNA <213> Homo sapiens <400> 502 uggacaaaug auuagauuag auuguguuau aaaccaaaga uuauaguuau uccaauuaug 60 ugcauuugag auccacu 77 <210> 503 <211> 82 <212> RNA <213> Homo sapiens <400> 503 cagucagugu cgagaaccuu auauuguucu gaagagaggu ggugacuuaa aaaucaugcu 60 caauaggauu acgcugaggc cc 82 <210> 504 <211> 94 <212> RNA <213> Homo sapiens <400> 504 uggaucgaug augacuuuca uacaugcauu ccuuggaaag cugaacaaaa ugagugaaaa 60 cucuauaccg ucauccucgu cgaacugagg ucca 94 <210> 505 <211> 135 <212> RNA <213> Homo sapiens <400> 505 uguccuugac uuggguagag ugaugucugg uuggugcugc cuaucucaua uaagccaggg 60 acaaaucaau gccuuauuua uuccagcuug gcuuuugguc ugugcccaua ccugguuuau 120 gccuuggaca caugg 135 <210> 506 <211> 149 <212> RNA <213> Homo sapiens <400> 506 cagauggcuc cgaaguuuac auccuauuag guuugugcaa aaguaauugc ggauuuugcc 60 auuaaaagua auggcaaaaa uagcaauuau uuuuguacca gccuaguauc uuuucuccuu 120 cuaccaaacu uugucccuga gccaucuca 149 <210> 507 <211> 208 <212> RNA <213> Homo sapiens <400> 507 aagacuauac uuucagggau cauuucuaca uuuccgggua auuucuuuga acauguggag 60 caccggaaac caccaggagg aggcacagca uuuucucugg agcgugaagc caguucuugg 120 uguugcugca uagcaacugc cauuugccuu ugaugaucau ucuucuuuuc cuuuaggaga 180 auaagagggg gagaacccag ucugaggg 208 <210> 508 <211> 59 <212> RNA <213> Homo sapiens <400> 508 cgggcucugg gugcaguggg gguucccacg ccgcggcaac caccacuguc ucuccccag 59 <210> 509 <211> 23 <212> RNA <213> Homo sapiens <400> 509 uuuguaugga uaugugugug uau 23 <210> 510 <211> 128 <212> RNA <213> Homo sapiens <400> 510 aggucauuuc aaagaggucu ugugaggcug ugaaaccaag agcucuuaac acugcgacca 60 aagauggaag uucucuauag gaugccaugg cauuugaugg ugcuauguuu ucuugaggag 120 auauaaga 128 <210> 511 <211> 23 <212> RNA <213> Homo sapiens <400> 511 ccagccacgg acugagagug cau 23 <210> 512 <211> 103 <212> RNA <213> Homo sapiens <400> 512 aucccuuuau aguucccgag caugacgauu ggguguucac augcaugugu gagauguacc 60 acccucgcau cuuguuagac guuggcacau uacccgucug acc 103 <210> 513 <211> 24 <212> RNA <213> Homo sapiens <400> 513 guuccacacu gacacugcag aagu 24 <210> 514 <211> 22 <212> RNA <213> Homo sapiens <400> 514 aguauucugu accagggaag gu 22 <210> 515 <211> 106 <212> RNA <213> Homo sapiens <400> 515 gcgcagcgcc cugucuccca gccugaggug cagugcugca ucucugguca guugggaguc 60 ugagaugaag cacuguagcu caggaagaga gaaguuguuc ugcagc 106 <210> 516 <211> 75 <212> RNA <213> Homo sapiens <400> 516 uaucugugau gaucuuaucc cgaaccugaa cuucuguuga aaaaaaaaaa cuuuuacgga 60 ucuggcuucu gagau 75 <210> 517 <211> 102 <212> RNA <213> Homo sapiens <400> 517 auaaucuugu aguucauaag caugaugauu gccuuuucac acucguauga gaugugccuc 60 ccuugaaccu uguuaugaug uuggcacauu acccaucuga ug 102 <210> 518 <211> 131 <212> RNA <213> Homo sapiens <400> 518 ugggaggcug auacacaaau ugggcugaaa uacugcucua cuugucacca ugccucccua 60 gaauaaacug ccuuuugaug accgggacga auugagugaa aucguaacgg acagauacgg 120 ggcagacaga u 131 <210> 519 <211> 22 [[ID=�6]]<212> RNA <213> Homo sapiens <400> 519 ccagagaugg uugccuuccu au 22 <210> 520 <211> 23 <212> RNA <213> Homo sapiens <400> 520 cggggccaug gagcagccug ugu 23 <210> 521 <211> 109 <212> RNA <213> Homo sapiens <400> 521 auucuuuugc uguucguaag cauaaggauc agguauucau ggucaugugu aagacgugcc 60 ucccuccaac cuuguuacga uguggacguc agcacauacc cauuugaug 109 <210> 522 <211> 110 <212> RNA <213> Homo sapiens <400> 522 gcugcuggaa gguguaggua cccucaaugg cucaguagcc aguguagauc cugucuuucg 60 uaaucagcag cuacaucugg cuacuggguc ucugauggca ucuucuagcu 110 <210> 523 <211> 75 <212> RNA <213> Homo sapiens <400> 523 uggaccaaug augugaaugg aaugcaucug aauaaaaauu augaucaauc aguuuuugga 60 acaacugagg uccac 75 <210> 524 <211> 108 <212> RNA <213> Homo sapiens <400> 524 aggccccugu aguucccgag cacgaugacu ggguguucac gugcacgugu gggaugugcc 60 acccucugaa ccuuguuacg auguuggcac auuacccugg accugacc 108 <210> 525 <211> 97 <212> RNA <213> Homo sapiens <400> 525 uauuaugcca ugacauugug ucaauaugcg augauguguu gugauggcac agcgucauca 60 cguggugacg caacaucaug acguaagacg ucacaac 97 <210> 526 <211> 96 <212> RNA <213> Homo sapiens <400> 526 uucaaaaaag accauauauc cuugaagagu aacugcugaa cuuauucacu ggcagugggc 60 cuuauagcac agugaaugac cagguuagag acaugc 96 <210> 527 <211> 215 <212> RNA <213> Homo sapiens <400> 527 aagacuauac uuucagggau cauuucuaua guuaguugcu agagaaguuu cucuggacau 60 guggagcacc agaaaccaug agaaggagau guaguguucu cuccggagca ugaagcuggc 120 ucuugguguu gcuucgcugc accugccauu ugccauugac aaucauucuu cucuuccucu 180 gggagaguaa ggaggagagg acacagucug agugg 215 <210> 528 <211> 23 <212> RNA <213> Homo sapiens <400> 528 cugcagccac uuggggaacu ggu 23 <210> 529 <211> 58 <212> RNA <213> Homo sapiens <400> 529 ugcuggcuca uuucauaugu gugcugagaa aauucacaca uaugaaguga gccagcac 58 <210> 530 <211> 22 <212> RNA <213> Homo sapiens <400> 530 ccugacaccc caucugcccu ca 22 <210> 531 <211> 21 <212> RNA <213> Homo sapiens <400> 531 uuacacagcu ggacagaggc a 21 <210> 532 <211> 110 <212> RNA <213> Homo sapiens <400> 532 aguauaauua uuacauaguu uuugaugucg cagauacugc aucaggaacu gauuggauaa 60 gaaucaguca ccaucaguuc cuaaugcauu gccuucagca ucuaaacaag 110 <210> 533 <211> 18 <212> RNA <213> Homo sapiens <400> 533 gguggggggu guuguuuu 18 <210> 534 <211> 98 <212> RNA <213> Homo sapiens <400> 534 aggagccacc uuccgagccu ccaguaccac gugucagggc cacaugagcu gggccucgug 60 ggccugaugu ggugcugggg ccucaggggu cugcucuu 98 <210> 535 <211> 22 <212> RNA <213> Homo sapiens <400> 535 uagcaccauu ugaaaucggu ua 22 <210> 536 <211> 104 <212> RNA <213> Homo sapiens <400> 536 auccuuuugu aguucaugag caugaugauu gguuguucac guacaugugu gagauguguc 60 acccucgaac cuuguggcaa uguuggaaua uuaccugucu gaca 104 <210> 537 <211> 120 <212> RNA <213> Homo sapiens <400> 537 gauucacagc agaaagacag cuaaucuagu gugcuagcug uagagcaagu uugcugcaaa 60 caccucaagg agggucucug gccaaaugag uagaaucuga caguaauccu ugcuaaaagu 120 <210> 538 <211> 71 <212> RNA <213> Homo sapiens <400> 538 cuacaaugau ggcaauaugu uucaucgaca gcaguucacc cauugagugu ugauaccgug 60 ggucugagug a 71 <210> 539 <211> 81 <212> RNA <213> Homo sapiens <400> 539 auucaggccg guccugcaga gaggaagccc uuccaauacc uguaagcaga agggcuuccu 60 cucugcagga ccggccugaa u 81 <210> 540 <211> 74 <212> RNA <213> Homo sapiens <400> 540 uggaccaaug augacaaaua ccggcguaug agucuuggau gaugaauaau acgugucugg 60 aacucugagg ucca 74 <210> 541 <211> 47 <212> RNA <213> Homo sapiens <400> 541 gccuaggagu ccuuggucag uggggacaug gagaaggcuu cugagga 47 <210> 542 <211> 81 <212> RNA <213> Homo sapiens <400> 542 gugagggacu gggauuugug gggcgaggag ggaccuguac uagccauggu ucugaucaca 60 uaugucccau cccuccauca g 81 <210> 543 <211> 73 <212> RNA <213> Homo sapiens <400> 543 guocugaug aagcuaugu ugguagggac aacuaaggu guugaugaau gcuacagcu 60 weather cac 73 <210> 544 <211> 72 <212> RNA <213>智人 <400> 544 cugggaaug gcaaggaac cguuaccauu acugaguuua guaaugua ugguucucuu 60 gcuauaccca has 72 <210> 545 <211> 22 <212> RNA <213>智人 <400> 545 Gugagccagu ggaoggaga gg 22 <210> 546 <211> 81 <212> RNA <213>智人 <400> 546 accuccuccc gugaaucaca auuguccuua auagcaaucc uaaaugcca uuaaggacau 60 oogaouga uggaggagg a 81 <210> 547 <211> 96 <212> RNA <213>智人 <400> 547 aacuaucuu agguagaugc agaaguacu acgguuuuug caguagaag uaauggcaaa 60 gaccgugacu acuuugca cagccuaaua guucu 96 <210> 548 <211> 149 <212> RNA <213> Homo sapiens <400> 548 auccaagggg auucccucuc caagggaaca ugcagugccc cucucaggaa aguaacaacc 60 uggaauagaa ucuggcaugc cuaaggucuu ugaggaauag aggaauagag gaugcuuguu 120 uccucugccu uccuuggcug ccuacaugg 149 <210> 549 <211> 72 <212> RNA <213> Homo sapiens <400> 549 acaacauguu uuuaggacau guaugucugg ugcaauaauu gggacauacu uaugcuaaaa 60 aaauuagugu uc 72 <210> 550 <211> 100 <212> RNA <213> Homo sapiens <400> 550 acuuuauacg uguaauugug augaggaugg auagcaagga agccgcuccc accugacccu 60 cacggccucc guguuaccug uccucuaggu gggacgcucg 100 <210> 551 <211> 83 <212> RNA <213> Homo sapiens <400> 551 agcuuaggua ccaauuuggc cacaaugggu uagaacacua uuccauugug uucuuaccca 60 ccauggccaa aauugggccu aag 83 <210> 552 <211> 76 <212> RNA <213> Homo sapiens <400> 552 guccucugau gacuucaugu uagugccacc ugucugggcc acggagaacc caugauggaa 60 cugagaaucu gaggaa 76 <210> 553 <211> 22 <212> RNA <213> Homo sapiens <400> 553 uugcucugag cuccgagaaa gc 22 <210> 554 <211> 92 <212> RNA <213> Homo sapiens <400> 554 acccuuuugu aguucauaag caggaugacu gaguuuucau gcacuugugu gagaugcgcc 60 ucccucaaug uuggcacauu accuaucuga ug 92 <210> 555 <211> 68 <212> RNA <213> Homo sapiens <400> 555 cuucaauuuu auuuuaaaac ggugagauuu uguuuugucu gagaaaaucu cgcuguuuua 60 gacugagg 68 <210> 556 <211> 217 <212> RNA <213> Homo sapiens <400> 556 aagacuauac uuucagggau cauuucuaua guguguuacu agagaaguuu cucugaacgu 60 guagagcacc gaaaaccacg aggaagagag guagcguuuu cuccugagcg ugaagccggc 120 uuucuggcgu ugcuuggcug caacugccgu cagccauuga ugaucguucu ucucuccgua 180 uuggggagug agagggagag aacgcggucu gaguggu 217 <210> 557 <211> 22 <212> RNA <213> Homo sapiens <400> 557 aauguggacu ggugugacca aa 22 <210> 558 <211> 22 <212> RNA <213> Homo sapiens <400> 558 ugggaacuua guagagguuu aa 22 <210> 559 <211> 67 <212> RNA <213> Homo sapiens <400> 559 auggaggugg agagucauca gcagcacuga gcaggcagug uugucugcug aguuuccacg 60 ucauuug 67 <210> 560 <211> 133 <212> RNA <213> Homo sapiens <400> 560 aagccagcca augaaucugc uuaccugauu guguuugugc agacauacuu uaaaaacugg 60 caauaguaaa gccauguuac gagccuuaag gacauugaag ucguuaaggu cccugagaau 120 ggcuauaaca aau 133 <210> 561 <211> 22 <212> RNA <213> Homo sapiens <400> 561 ucugcaagug ucagaggcga gg 22 <210> 562 <211> 23 <212> RNA <213> Homo sapiens <400> 562 ugugcaaauc uaugcaaaac uga 23 <210> 563 <211> 22 <212> RNA <213> Homo sapiens <400> 563 caaucagcaa guauacugcc cu 22 <210> 564 <211> 81 <212> RNA <213> Homo sapiens <400> 564 uaaaugaaaa aguaguaguc aaauaugcag aucuauguca uauauacaga uauguauaug 60 ugacugcuac uuuuuuguuu a 81 <210> 565 <211> 17 <212> RNA <213> Homo sapiens <400> 565 cagccugaca ggaacag 17 <210> 566 <211> 127 <212> RNA <213> Homo sapiens <400> 566 uucuaaagug uugaguucag uccagggugg auccccugcu cuguuaauug aacuggaaca 60 uuuaaacugg cuaggcaaaa ugccuacaua gaaagcauua cucuuuauuc auccccagcc 120 uacaaaa 127 <210> 567 <211> 22 <212> RNA <213> Homo sapiens <400> 567 caaaguuuaa gauccuugaa gu 22 <210> 568 <211> 22 <212> RNA <213> Homo sapiens <400> 568 cuucugauca agauuugugg ug 22 <210> 569 <211> 22 <212> RNA <213> Homo sapiens <400> 569 gaauguugcu cggugaaccc cu 22 <210> 570 <211> 22 <212> RNA <213> Homo sapiens <400> 570 gugcauggcu guauauauaa ca 22 <210> 571 <211> 73 <212> RNA <213> Homo sapiens <400> 571 ugggcuuugc ccgcuuucug agcuggaccc ucucucuacc ucuggugcag aacuacagcg 60 gaaggaaucu cug 73 <210> 572 <211> 71 <212> RNA <213> Homo sapiens <400> 572 gcauuggaau aggggauauc ucagcauguu gagcccuguc ucuggggagc ugacuucuac 60 cucuuccaaa g 71 <210> 573 <211> 107 <212> RNA <213> Homo sapiens <400> 573 auccaaggug auuccuucuc caagggggac auccagugac ccucucagga aguagcaacu 60 uggaauagaa uaguccagga guuccaggac cagccuggcc aauaugg 107 <210> 574 <211> 22 <212> RNA <213> Homo sapiens <400> 574 gcccucuguc accuugcaga cg 22 <210> 575 <211> 21 <212> RNA <213> Homo sapiens <400> 575 aagccucugu ccccacccca g 21 <210> 576 <211> 22 <212> RNA <213> Homo sapiens <400> 576 uuagccaauu guccaucuuu ag 22 <210> 577 <211> 104 <212> RNA <213> Homo sapiens <400> 577 aucuuuuugu aguucaugag cgugaugacu gaguguucau gugcaugugu gaggcgugcc 60 acccuuaaac cuuguuauaa caucagcaca uuacccacau gaca 104 <210> 578 <211> 21 <212> RNA <213> Homo sapiens <400> 578 caucccuugc augguggagg g 21 <210> 579 <211> 125 <212> RNA <213> Homo sapiens <400> 579 cuggagacua agaaaccagu ccuugaaguc aagcugacuc ugcuuuuagc cuccuaaauu 60 aaaagauaga uagaauaggu cuuguuugca aaauaaauuc aagaucuacu caucuaucaa 120 uagca 125 <210> 580 <211> 22 <212> RNA <213> Homo sapiens <400> 580 cagugcaaug uuaaaagggc au 22 <210> 581 <211> 21 <212> RNA <213> Homo sapiens <400> 581 cuacaggcug gaaugggcuc a 21 <210> 582 <211> 115 <212> RNA <213> Homo sapiens <400> 582 agcacuugug uuugcuuuug uuugacuugu ggacaaagac uuauaguaga caggcacgaa 60 aaaauaaauc cucuuuugca acccaugagu uguuauacau gcaagaagga auauu 115 <210> 583 <211> 22 <212> RNA <213> Homo sapiens <400> 583 ugcccugugg acucaguucu gg 22 <210> 584 <211> 24 <212> RNA <213> Homo sapiens <400> 584 cuucugccug cauucuacuc ccag 24 <210> 585 <211> 22 <212> RNA <213> Homo sapiens <400> 585 cuauacaacu uacuacuuuc cc 22 <210> 586 <211> 96 <212> RNA <213> Homo sapiens <400> 586 cuucugcuaa gguuuacacu auagaugcag gaaaaaaaau guccucacac ugucugucug 60 auuguggcag cugagauuga auagagaaau auaggg 96 <210> 587 <211> 23 <212> RNA <213> Homo sapiens <400> 587 ccggggcaga uugguguagg gug 23 <210> 588 <211> 82 <212> RNA <213> Homo sapiens <400> 588 gggucaauga ugagaaccuu auaauguucu gaagagaggu gaugacuuaa aaaucaugcu 60 caauaggauu acgcugaggc cc 82 <210> 589 <211> 76 <212> RNA <213> Homo sapiens <400> 589 uacuugaaga gaaguuguuc gugguggauu cgcuuuacuu augacgaauc auucacggac 60 aacacuuuuu ucagua 76 <210> 590 <211> 23 <212> RNA <213> Homo sapiens <400> 590 ugacccccau gucgccucug uag 23 <210> 591 <211> 23 <212> RNA <213> Homo sapiens <400> 591 ccugcagcga cuugauggcu ucc 23 <210> 592 <211> 22 <212> RNA <213> Homo sapiens <400> 592 augcaggccu guguacagca cu 22 <210> 593 <211> 101 <212> RNA <213> Homo sapiens <400> 593 gcgagaagau cucaugcugu gacucucugg agggaagcac uuucuguugu cugaaagaaa 60 acaaagcgcu ucucuuuaga guguuacggu uugagaaaag c 101 <210> 594 <211> 22 <212> RNA <213> Homo sapiens <400> 594 ugugacaaua gagaugaaca ug 22 <210> 595 <211> 82 <212> RNA <213> Homo sapiens <400> 595 uugcugcaaa aauaauugca guuuuugcca uuauuuuuaa uaauuauaau aauggccaaa 60 acugcaguua uuuuugcacc aa 82 <210> 596 <211> 72 <212> RNA <213> Homo sapiens <400> 596 ucugcucuga gagagcucga uggcaggugc cuccguguug ccgaacccuc cuacgcugcu 60 cucucacucc ag 72 <210> 597 <211> 20 <212> RNA <213> Homo sapiens <400> 597 ucguuugccu uuuucugcuu 20 <210> 598 <211> 22 <212> RNA <213> Homo sapiens <400> 598 gugacugaua ccuuggaggc au 22 <210> 599 <211> 85 <212> RNA <213> Homo sapiens <400> 599 cgcuggcgac gggacauuau uacuuuuggu acgcgcugug acacuucaaa cucguaccgu 60 gaguaauaau gcgccgucca cggca 85 <210> 600 <211> 211 <212> RNA <213> Homo sapiens <400> 600 aagaugacac uuugaggcau cgugucuaug guucauuacu acagaagcuu cucuggaugu 60 guaaagcaca ggaaaccagg cagaggaggc acagggugcu cuccagaacg agaagccagc 120 uccuggaguu guuugcugca acugccauuc cccguugaug accaugcucu uccuucagaa 180 gagggagagu gagaggacca aguccaagug g 211 <210> 601 <211> 22 <212> RNA <213> Homo sapiens <400> 601 ucccaagggu gagaugcugc ca 22 <210> 602 <211> 23 <212> RNA <213> Homo sapiens <400> 602 aauguggaag uggucugagg cau 23 <210> 603 <211> 71 <212> RNA <213> Homo sapiens <400> 603 ggagaggagg caagaugcug gcauagcugu ugaacuggga accugcuaug ccaacauauu 60 gccaucuuuc c 71 <210> 604 <211> 66 <212> RNA <213> Homo sapiens <400> 604 ggcugccagg gaggcugguu uggaggaguc ugguggccug uucucuucac cugccucugc 60 cugcag 66 <210> 605 <211> 80 <212> RNA <213> Homo sapiens <400> 605 gguauuuaaa agguagauuu uccuucuaug guuacguguu ugaugguuaa ucauagagga 60 aaauccacgu uuucaguauc 80 <210> 606 <211> 22 <212> RNA <213> Homo sapiens <400> 606 uaacacuguc ugguaacgau gu 22 <210> 607 <211> 22 <212> RNA <213> Homo sapiens <400> 607 aucaaauaag gacuagucug ca 22 <210> 608 <211> 21 <212> RNA <213> Homo sapiens <400> 608 aggcccuguc cucugcccca g 21 <210> 609 <211> 24 <212> RNA <213> Homo sapiens <400> 609 ccucacccag cucucuggcc cucu 24 <210> 610 <211> 107 <212> RNA <213> Homo sapiens <400> 610 auccuuuugu gguucauaag caugaugauu agauuuucau gcuauugggu gagauaugcc 60 uuccucagac uuuguuacag cauaggcaca uuacaaccug ucugaua 107 <210> 611 <211> 110 <212> RNA <213> Homo sapiens <400> 611 ccgcagagug ugacuccugu ucuguguaug gcacugguag aauucacugu gaacagucuc 60 agucagugaa uuaccgaagg gccauaaaca gagcagagac agauccacga 110 <210> 612 <211> 23 <212> RNA <213> Homo sapiens <400> 612 agcucggucu gaggccccuc agu 23 <210> 613 <211> 17 <212> RNA <213> Homo sapiens <400> 613 uggagagaaa ggcagua 17 <210> 614 <211> 72 <212> RNA <213> Homo sapiens <400> 614 acuccaugau gaacccaaaa ugccaaguau augacugaac uuacaaguga uaccaucuua 60 cgacugaaga gu 72 <210> 615 <211> 105 <212> RNA <213> Homo sapiens <400> 615 auccuuuugu aguucaugag gaugaugguu ggguguuuca cacaugugug ugaaauguac 60 cacccucaaa ccuuguuaca augucagcac auuaccugcc ugacc 105 <210> 616 <211> 78 <212> RNA <213> Homo sapiens <400> 616 uggccgauuu uggcacuagc acauuuuugc uugugucucu ccgcucugag caaucaugug 60 cagugccaau augggaaa 78 <210> 617 <211> 21 <212> RNA <213> Homo sapiens <400> 617 acuccaguuu uaguucucuu g 21 <210> 618 <211> 23 <212> RNA <213> Homo sapiens <400> 618 ucagcaccag gauauuguug gag 23 <210> 619 <211> 134 <212> RNA <213> Homo sapiens <400> 619 ucgaugggug ggauaauccu uaccuguucc ucguuuugga gggcagauag aacaugauga 60 uuggagaugc augaaaugug auuaaugccu cugccuaauc aggacuugca acacccugag 120 uacuccucuc ugau 134 <210> 620 <211> 103 <212> RNA <213> Homo sapiens <400> 620 auccuuuugu aguucauaag ugugaugauu agguuuucac auuugugugu gagauguauc 60 ucccucaaac auuuuaugac aucggcauau uauccuucug aug 103 <210> 621 <211> 22 <212> RNA <213> Homo sapiens <400> 621 cuccuauaug augccuuucu uc 22 <210> 622 <211> 21 <212> RNA <213> Homo sapiens <400> 622 uaaaguaaau augcaccaaa a 21 <210> 623 <211> 22 <212> RNA <213> Homo sapiens <400> 623 uugagaauga ugaaucauua gg 22 <210> 624 <211> 215 <212> RNA <213> Homo sapiens <400> 624 aagacuauac uuucagggau cauuuguaua guucguuacu agagaauuuu cucugaaugu 60 guagaacacc agaaaccaca aggaggaggc gcagcguucu cuccugagcg ugaagccggg 120 uccugguguu gcuucacugc aacugccauu ugccauugau gauuguucuu cucuuccuuu 180 gggagaguaa gaggcaaagg augcagucug aaugg 215 <210> 625 <211> 22 <212> RNA <213> Homo sapiens <400> 625 aaccaucgac cguugagugg ac 22 <210> 626 <211> 59 <212> RNA <213> Homo sapiens <400> 626 ggggccaggc agggaggugg gaccaugggg gccuugcugu gugaccaccg uuccugcag 59 <210> 627 <211> 104 <212> RNA <213> Homo sapiens <400> 627 aucuuuuugu aguucauaag caugaugauu auguuuuuac auucaugugu aagaugugcc 60 ucccucaaac cuuguuauga ugucagcaua uuaccugucu gaug 104 <210> 628 <211> 21 <212> RNA <213> Homo sapiens <400> 628 acugacagga gagcauuuug a 21 <210> 629 <211> 133 <212> RNA <213> Homo sapiens <400> 629 aagccagcca augaaucugc uuaccugauu guguuugugc agacauacuu uaaaaacugg 60 caauaguaaa gccauguuac gagccuuaag gacauugaag ucguuaaggu cccugagaau 120 ggcuauaaca aau 133 <210> 630 <211> 22 <212> RNA <213> Homo sapiens <400> 630 aguauucugu accagggaag gu 22 <210> 631 <211> 133 <212> RNA <213> Homo sapiens <400> 631 uccaucuguu uggcagaccu ggagcaguua gugucugcug cuaagguuuc cauuacagau 60 gugagaaaaa aaaguguucu ucugcuuucu gucugucuca guggcaacca agauugaaug 120 ggggauauga gag 133 <210> 632 <211> 104 <212> RNA <213> Homo sapiens <400> 632 auucuuuugu aauucauaag caugaugacu cgguauucac gugcaugugu gagaugugcc 60 acccuggaac cuuguugcaa cgucagcaca uuaugggucu gaca 104 <210> 633 <211> 72 <212> RNA <213> Homo sapiens <400> 633 augaccaaug gugagagugu aucaugaagc aaggaaugug auuaauccag uucuguaaac 60 ccaaguucca gu 72 <210> 634 <211> 24 <212> RNA <213> Homo sapiens <400> 634 uuggaagcuu ggaccaacua gcug 24 <210> 635 <211> 105 <212> RNA <213> Homo sapiens <400> 635 auccuuuugu aguucaugag caugaccauc gaguguuuac augcaugugu gagauaugac 60 accuucugaa ccuuguuacg gaguuggcau guuacccauc uaacc 105 <210> 636 <211> 202 <212> RNA <213> Homo sapiens <400> 636 aagauuauau uuucagggau cauuucuaua guuugucacu agggaaguuc cucugaaugu 60 guagagcacc agaaacauga ggaagaggca caggguucuc uccugagugu gaagcuggcu 120 cuuggcgcug cuuuccugca acugcuauuu gccauucgug auuguggaga gucagaggga 180 gaggaugaug cagucugagu gg 202 <210> 637 <211> 85 <212> RNA <213> Homo sapiens <400> 637 auccuuuugu aguucaugag caugaugauu ggguguucac gugcaugugu gagaugugac 60 acccuugcac auuacucgcc ugacc 85 <210> 638 <211> 22 <212> RNA <213> Homo sapiens <400> 638 agacccuggu cugcacucua uc 22 <210> 639 <211> 22 <212> RNA <213> Homo sapiens <400> 639 uaacaaacac cuguaaaaca gc 22 <210> 640 <211> 110 <212> RNA <213> Homo sapiens <400> 640 ugcccaguga ugacaccauc cuugcucccc gugcccccca ggggcuaugg gcgacaccau 60 ggcugccccu gggcugggcc aguggggcca augcccaggg gcugagggca 110 <210> 641 <211> 72 <212> RNA <213> Homo sapiens <400> 641 cagccaggag ggaaggggcu gagaacagga ccugugcuca cuggggccug caugacccuu 60 cccuccccac ag 72 <210> 642 <211> 68 <212> RNA <213> Homo sapiens <400> 642 acucacugau gaguagcuuc ugacuuucau ucugaguuug cugaacccag augccauucc 60 ugggaagg 68 <210> 643 <211> 103 <212> RNA <213> Homo sapiens <400> 643 auccuuuugu gguucauuag cuugauauug gguuuucaca cuauucuaug agaugugccu 60 cccucaaaac uuguuacaac auugacacau uacccuucug aug 103 <210> 644 <211> 81 <212> RNA <213> Homo sapiens <400> 644 uauuaauaug gaagggagaa gagcuuuaau gauuggaguc auuuucagag cauuaaagcu 60 cuucucccuu ccauauuaau g 81 <210> 645 <211> 87 <212> RNA <213> Homo sapiens <400> 645 ucucaggcug ugacccucua aagggaagcg cuuucugugg ucagaaagaa aagcaagugc 60 uuccuuuuag aggguuaccg uuuggga 87 <210> 646 <211> 21 <212> RNA <213> Homo sapiens <400> 646 uucuuuguuu uuaauucaca g 21 <210> 647 <211> 21 <212> RNA <213> Homo sapiens <400> 647 uuuuaaggac acugagggau c 21 <210> 648 <211> 75 <212> RNA <213> Homo sapiens <400> 648 gaauguggga aagagaaaga acaaguaaaa ggaauuuuca uuuuccagcc ccuaauuguu 60 cugucuuucu cccag 75 <210> 649 <211> 60 <212> RNA <213> Homo sapiens <400> 649 ucggcuaagg aaguccugug cucaguuuug uagcaucaaa acuaggauuu cucuuguuac 60 <210> 650 <211> 71 <212> RNA <213> Homo sapiens <400> 650 uggaucgaug augacugcug guggcguaug agucauaugc gaugaauacg ugucuagaac 60 ucugaggucc a 71 <210> 651 <211> 67 <212> RNA <213> Homo sapiens <400> 651 cccggugugu guguagagga agaagggaag cugggaaccu gacugccucu cccucuuuac 60 ccacuag 67 <210> 652 <211> 26 <212> RNA <213> Homo sapiens <400> 652 aaguaguugg uuuguaugag augguu 26 <210> 653 <211> 21 <212> RNA <213> Homo sapiens <400> 653 aucacauugc cagggauuuc c 21 <210> 654 <211> 104 <212> RNA <213> Homo sapiens <400> 654 auucuuuugu aguucuuagg cacgaugauu ggguguucau gugcauguuu gagaugugcc 60 ucccucaaac cuuguucuua caucagcacc uuacacgucu aaca 104 <210> 655 <211> 18 <212> RNA <213> Homo sapiens <400> 655 cauucaacua gugauugu 18 <210> 656 <211> 53 <212> RNA <213> Homo sapiens <400> 656 gccuucucuu cccaguucuu ccuggagucg gggaaaagcu ggguugagaa ggu 53 <210> 657 <211> 104 <212> RNA <213> Homo sapiens <400> 657 aguuuuucau aguucauaag caugaugagu ggguuuucau guucaugugu gaggugugcc 60 ucccucaaac cuuguuauga ugucaacaca uugcccaucu gaug 104 <210> 658 <211> 75 <212> RNA <213> Homo sapiens <400> 658 ugcagaugau guaaaagaau auuugcuauc ugagagaugg ugaugacauu uuaaaccacc 60 aagaucgcug augca 75 <210> 659 <211> 21 <212> RNA <213> Homo sapiens <400> 659 gcugcaccgg agacugggua a 21 <210> 660 <211> 23 <212> RNA <213> Homo sapiens <400> 660 cuacccucgg ucugcuuacc aca 23 <210> 661 <211> 74 <212> RNA <213> Homo sapiens <400> 661 agcaauugga gaagauugca gaguaaguuc cugauuaaga aauggaauuu acucugcaau 60 cuucuccaau ugcu 74 <210> 662 <211> 98 <212> RNA <213> Homo sapiens <400> 662 aggagccacc uuccgagccu ccaguaccac gugucagggc cacaugagcu gggccucgug 60 ggccugaugu ggugcugggg ccucaggggu cugcucuu 98 <210> 663 <211> 86 <212> RNA <213> Homo sapiens <400> 663 cucaccucau ucauuuaccu ucucuuacag aucacuuuuc ugcacuggac agugaucugu 60 aagagaaagu aaaugaaaga ggugag 86 <210> 664 <211> 21 <212> RNA <213> Homo sapiens <400> 664 aaaaguaauu gcaguuuuug c 21 <210> 665 <211> 85 <212> RNA <213> Homo sapiens <400> 665 uccuccccgg agccaggaug cagcucaagc cacagcaggg uguuuagcgc ucuucagugg 60 cuccagauug uggcgcuggu gcagg 85 <210> 666 <211> 82 <212> RNA <213> Homo sapiens <400> 666 gggucaauga ugagaaccgu auauuguccu gaagagcggu gaugacuuaa aaauaaugcu 60 caauaggauu acgcugaggc cc 82 <210> 667 <211> 19 <212> RNA <213> Homo sapiens <400> 667 ugagguggua ggauguaga 19 <210> 668 <211> 90 <212> RNA <213> Homo sapiens <400> 668 aagacccuuc agcugcaaac aacagcuucc uugguaguuu augcagccug uuucuuguau 60 gggcugcucu aagggaccau ggagacaggc 90 <210> 669 <211> 22 <212> RNA <213> Homo sapiens <400> 669 agcuguaauu agucaguuuu cu 22 <210> 670 <211> 49 <212> RNA <213> Homo sapiens <400> 670 uucccagcca acgcaccaaa aaugauaugg gucuguuguc uggagaaac 49 <210> 671 <211> 100 <212> RNA <213> Homo sapiens <400> 671 auacuuuugu aggucauaag cugaggauug gguuuucaug cucuugugug agauaugcuu 60 cucucaaacc uucugaccug ggcacauuac ccagcuaaug 100 <210> 672 <211> 20 <212> RNA <213> Homo sapiens <400> 672 ccugcguguu uucuguccaa 20 <210> 673 <211> 102 <212> RNA <213> Homo sapiens <400> 673 uuccuguugg uuccuaagug ugaugauugg guuuucacau ucauguguga caugugccuc 60 ccucaaaucu ugugaugaug ucggcacgug acccaucuga cg 102 <210> 674 <211> 100 <212> RNA <213> Homo sapiens <400> 674 cccccagaau cugucaggca ccagccaggc auugcucagc ccguuucccu cugggggagc 60 aaggaguggu gcuggguuug ucucugcugg gguuucuccu 100 <210> 675 <211> 21 <212> RNA <213> Homo sapiens <400> 675 gcuaguccug acucagccag u 21 <210> 676 <211> 76 <212> RNA <213> Homo sapiens <400> 676 acaaugauga cuuaaauuac uuuuugccgu uuacccagcu gagguugucu uugaagaaau 60 aauuuuaaga cugaga 76 <210> 677 <211> 21 <212> RNA <213> Homo sapiens <400> 677 cacaagguau ugguauuacc u 21 <210> 678 <211> 130 <212> RNA <213> Homo sapiens <400> 678 uggacauuua uuuuuauuca guuuuuucuc aaggugaagg uaacuguuug uagauguccu 60 agagaaauau uguagcuuuc uguucacccu uugcaacuaa aaagcaugga cuguuccacu 120 acugagauuu 130 <210> 679 <211> 131 <212> RNA <213> Homo sapiens <400> 679 cuucccauuu auuugcugcu auagucucau aaugauacaa gcaguuauau gcaugggaua 60 aaauaauauu gggacauugu aaauugaaau gaaguaacca uuuucaucuu uucugcaugg 120 acaagacauu g 131 <210> 680 <211> 60 <212> RNA <213> Homo sapiens <400> 680 ugugaaugac ccccuuccag agccaaaauc accagggaug gaggaggggu cuuggguacu 60 <210> 681 <211> 23 <212> RNA <213> Homo sapiens <400> 681 uugaagagga ggugcucugu agc 23 <210> 682 <211> 105 <212> RNA <213> Homo sapiens <400> 682 gaguucuaac guauuagguu ggugcaaaag uaauaguggu uuuugccauu aaaaguaaug 60 acaaaaacug uaauuacuuu uggaacaaua uuaauagaau uucag 105 <210> 683 <211> 72 <212> RNA <213> Homo sapiens <400> 683 ggucaaugau guaauggcau guauuagcug aauccaaagu ugaagugaau ucuaaaauua 60 caccaagacc uu 72 <210> 684 <211> 89 <212> RNA <213> Homo sapiens <400> 684 gucagcagug ccuuagcagc acguaaauau uggcguuaag auucuaaaau uaucuccagu 60 auuaacugug cugcugaagu aagguugac 89 <210> 685 <211> 134 <212> RNA <213> Homo sapiens <400> 685 uguucugaca ugggaagagu agcuucuggu ugguggagcc caucucacau uagccagaga 60 caaagcaaca ccuuguuuau cccggcuugg cuuuuggccu guguccauga cugguccaua 120 ccuuggacac augg 134 <210> 686 <211> 104 <212> RNA <213> Homo sapiens <400> 686 aucccuuugu aguucauaag cgugaugauu ggguguucau gcucauacau gagcugugcc 60 ucccucaagc uuuguuguga caucaucaua uuaccugucc gaug 104 <210> 687 <211> 22 <212> RNA <213> Homo sapiens <400> 687 accugccagc accucccugc ag 22 <210> 688 <211> 65 <212> RNA <213> Homo sapiens <400> 688 gagggcuagg uggggggcuu gaagccccga gaugccucac gucuucaccc cucucaccua 60 agcag 65 <210> 689 <211> 22 <212> RNA <213> Homo sapiens <400> 689 caucuuccag uacaguguug ga 22 <210> 690 <211> 67 <212> RNA <213> Homo sapiens <400> 690 gcgggcuucg cgggcgaagg caaagucgau uuccaaaagu gacuuuccuc acucccguga 60 agucggc 67 <210> 691 <211> 21 <212> RNA <213> Homo sapiens <400> 691 aguuaaugaa uccuggaaag u 21 <210> 692 <211> 135 <212> RNA <213> Homo sapiens <400> 692 ugccccugac cugggaagag aggggccugg cuggugguau ccaucucaua ccagcuaggg 60 augaagaaac cgcuugcuca ucccagccug gcuccugguc uaugcccaug ccugguucgu 120 gccuuggaca uauca 135 <210> 693 <211> 19 <212> RNA <213> Homo sapiens <400> 693 agagcuggcu gaagggcag 19 <210> 694 <211> 75 <212> RNA <213> Homo sapiens <400> 694 cagggguuug gggaaacggc cgcugaguga ggcgucggcu guguuucuca ccgcggucuu 60 uuccucccac ucuug 75 <210> 695 <211> 120 <212> RNA <213> Homo sapiens <400> 695 gauccaggga acccuagagc agggggaugg cagagcaaaa uucauggccu acagcugccu 60 cuugccaaac ugcacuggau uuugugucuc ccauucccca gagcugucug aggugcuuug 120 <210> 696 <211> 83 <212> RNA <213> Homo sapiens <400> 696 uucacaaugu cuauugaagg aucucaucac cuuuagagag cuguggucau gccccuuaaa 60 gugaauuugg agguuuuaua ccc 83 <210> 697 <211> 96 <212> RNA <213> Homo sapiens <400> 697 gugacccugg gcaaguuccu gaagaucaga cacaucagau cccuuaucug uaaaaugggc 60 augauccagg aaccugccuc uacgguugcc uugggg 96 <210> 698 <211> 86 <212> RNA <213> Homo sapiens <400> 698 cuuacaucac acacagaguu aacucaaaau ggacuaauuu uuccacuagu uaguccauuu 60 caaguuaacu cuguguguga uguagu 86 <210> 699 <211> 127 <212> RNA <213> Homo sapiens <400> 699 auuacuugaa aaucacuccc aggcuuuggc cauggcagca ggugagauuc aaggcccaga 60 gccuccaggg ccucagcuca ccgcacacug ccccgugugu gguggggaaa cccagacccc 120 aacaggu 127 <210> 700 <211> 22 <212> RNA <213> Homo sapiens <400> 700 caggucacgu cucugcaguu ac 22 <210> 701 <211> 149 <212> RNA <213> Homo sapiens <400> 701 caucaagacc cagcugaguc acugucacug ccuaccaauc ucgaccggac cucgaccggc 60 ucgucugugu ugccaaucga cucggcgugg cgucggucgu gguagauagg cggucaugca 120 uacgaauuuu cagcucuugu ucuggugac 149 <210> 702 <211> 136 <212> RNA <213> Homo sapiens <400> 702 ccucuucuca gaacacuucc ugggucugau ugguggccca gggagcuguc agagaagagc 60 agagcaaaug gccuucacuu uguagaugag auggcaggag gguggauugu uggucucagu 120 cagugguggg acagac 136 <210> 703 <211> 22 <212> RNA <213> Homo sapiens <400> 703 aucaugaugg gcuccucggu gu 22 <210> 704 <211> 129 <212> RNA <213> Homo sapiens <400> 704 aagcaggauu cagacuacaa uauagcuguu aagugcugua uugucauucc cccugcucaa 60 auuaaaguug uuucuuaacu auacccaucu gcuauucugu agcagccagg gaugcuuggu 120 cacauacau 129 <210> 705 <211> 136 <212> RNA <213> Homo sapiens <400> 705 gcuguccugg accuguuggc accacagaca guugcucugc ugugccugug gccucggggc 60 aaagagaaag uggcgauuuc uacacucagu gcucgggaac cagugggcac ugagaauggu 120 uuauggccug acauua 136 <210> 706 <211> 136 <212> RNA <213> Homo sapiens <400> 706 ucgucaggug ggagaauucu uacauguucc uccuuuugca aggcagauua gaacaugaug 60 auugggguuc gcauaauaug ugauuaacgu uucuguguaa ucaggacuug caacaucccg 120 aaugcccuua ccugac 136 <210> 707 <211> 72 <212> RNA <213> Homo sapiens <400> 707 uggaucaaug augacaaagu aucaugaaug agggauugug aauaaucuau uuuuaugaac 60 cuguggucaa au 72 <210> 708 <211> 22 <212> RNA <213> Homo sapiens <400> 708 uaugucugcu gaccaucacc uu 22 <210> 709 <211> 74 <212> RNA <213> Homo sapiens <400> 709 ugaggaugaa agacccauug aggagaaggu ucugcuggcu gagaaccuuc cucuccaugg 60 gucuuucauc cuca 74 <210> 710 <211> 101 <212> RNA <213> Homo sapiens <400> 710 auccuuuugu gguucauaag aauagggauu gggauuucac acucaugugu gagaugugcc 60 ucccuuaaac cuuaagaugu uggcacauua ccuauuugau g 101 <210> 711 <211> 104 <212> RNA <213> Homo sapiens <400> 711 auccuuuugu aguucauuag cauaaugauu ggguuuucac acucaggcgu gagaugugcc 60 ucucucaaac cuugcuacga uguuggcaca uugccuaucu ggca 104 <210> 712 <211> 21 <212> RNA <213> Homo sapiens <400> 712 aaaauuucuu ucacuacuua g 21 <210> 713 <211> 22 <212> RNA <213> Homo sapiens <400> 713 uuuuucauua uugcuccuga cc 22 <210> 714 <211> 129 <212> RNA <213> Homo sapiens <400> 714 cucauaccua aacccaagaa ucacuuucuu auagugauga uuuaaacaga ugcaaacagc 60 gagcacaucu ugucaccuuu gcgggacugu ggcugugccc cucgcaguaa auuuggaggu 120 ucuacaucc 129 <210> 715 <211> 77 <212> RNA <213> Homo sapiens <400> 715 uguuuaucuc uaggguugau cuauuagaau uacuuaucug agccaaagua auucaaguaa 60 uucaggugua gugaaac 77 <210> 716 <211> 212 <212> RNA <213> Homo sapiens <400> 716 aaugcuauac uuucaugggu cauuucuaua guuuguuauu agagaaguuu cucugaaugu 60 guugagcacc agaaaccacg aggagaugca gcauucucuc cugaacggga agccagcuuu 120 uggcauugcu uugaugcaac uaccauuugc cauugauggc aaugcaucgc uuccucuagg 180 aguguaagag ggaguggaug cagucagagu gg 212 <210> 717 <211> 88 <212> RNA <213> Homo sapiens <400> 717 accaaguuuc aguucaugua aacauccuac acucagcugu aauacaugga uuggcuggga 60 gguggauguu uacuucagcu gacuugga 88 <210> 718 <211> 96 <212> RNA <213> Homo sapiens <400> 718 uucaaaaaag accauauauc cuugaagagu aacugcugaa cuuauucacu ggcagugggc 60 cuuauagcac agugaaugac cagguuagag acaugc 96 <210> 719 <211> 22 <212> RNA <213> Homo sapiens <400> 719 auucugcauu uuuagcaagu uc 22 <210> 720 <211> 133 <212> RNA <213> Homo sapiens <400> 720 uucucaccua aacccaagaa ucacuguuuc uuauagcggu gguuuaaaca gaggugcaaa 60 cagcaaguga aucucgucgc cuuugcgggg cuguggccau gccccucaaa ggaaauuugg 120 aggcucuaca gcc 133 <210> 721 <211> 109 <212> RNA <213> Homo sapiens <400> 721 gcuuuuauau uguagguuuu ugcucaugca ccaugguugu cugagcaugc agcaugcuug 60 ucugcucaua ccccaugguu ucugagcagg aaccuucauu gucuacugc 109 <210> 722 <211> 97 <212> RNA <213> Homo sapiens <400> 722 aucugaguug ggaggguccc ucuccaaaug ugucuugggg ugggggauca agacacauuu 60 ggagagggaa ccucccaacu cggccucugc caucauu 97 <210> 723 <211> 115 <212> RNA <213> Homo sapiens <400> 723 ucuguuuauc accagauccu agaacccuau caauauuguc ucugcugugu aaauaguucu 60 gaguagugca auauugcuua uaggguuuug guguuuggaa agaacaaugg gcagg 115 <210> 724 <211> 140 <212> RNA <213> Homo sapiens <400> 724 auccaaggcg auucccucuc caaggggaca ucuagugccc cucucaggaa aguagcaacu 60 uggaauagaa ucuggcaugc cuaaggucuu ugaggaacag ggaugcuuau uuccucugcc 120 uuccuuggcu gccuacauag 140 <210> 725 <211> 77 <212> RNA <213> Homo sapiens <400> 725 ugauagggaa accaggcaag aaauauuguc uccucaaguu gcgacgagac aguaguucuu 60 gccugguuuc ucuauca 77 <210> 726 <211> 56 <212> RNA <213> Homo sapiens <400> 726 ccacugcaga gccugggaag ggagcugucc ggcuccccag gcucugcagu gggagg 56 <210> 727 <211> 72 <212> RNA <213> Homo sapiens <400> 727 ccuggugaug acagacgaca uugucagcca auccccaugu gguagugagg acauguccug 60 caguucugaa gg 72 <210> 728 <211> 128 <212> RNA <213> Homo sapiens <400> 728 ugcacuuaug uauguuuuug uuuaacuugu ggacaaagac uuuaggaaag gugcaaaaaa 60 uaaaucuucu uuugcaaccc agaacucauu guucaguaug aguuuugaua cauaucagaa 120 uggauacu 128 <210> 729 <211> 21 <212> RNA <213> Homo sapiens <400> 729 ucacgcggag agauggcuuu g 21 <210> 730 <211> 123 <212> RNA <213> Homo sapiens <400> 730 ugccccuuuu aagguugaca cagugcauua agcagaaggg uuaaguaagu cuccauaaaa 60 cccagagaag agaauguaaa gcuccucuuu ggaggagcua gacuccuguc uggagucaca 120 gcu 123 <210> 731 <211> 95 <212> RNA <213> Homo sapiens <400> 731 agugauauaa uagagggugc acaggcaugg gaggucaggu gagcucagcu cccugccuca 60 ccugagcucc cgugccugug cacccucuau uggcu 95 <210> 732 <211> 23 <212> RNA <213> Homo sapiens <400> 732 cggggccaug gagcagccug ugu 23 <210> 733 <211> 103 <212> RNA <213> Homo sapiens <400> 733 aggaauuuuu aacccgauca cuagauuauc uacaagggaa uuuuuuuuua auuuaaaaaa 60 uucccuugua gauaacccgg uggucagguu ggauggcucc aug 103 <210> 734 <211> 139 <212> RNA <213> Homo sapiens <400> 734 ugcacugcgu gguaucugca cucagcaguu uacuccugcu aggguguuca aaggucagug 60 ccauagaaau ccaguaucug guuucauugg uuuucuuggc uuugugcuug uuaaaccugg 120 uauuucuauu gauacagca 139 <210> 735 <211> 22 <212> RNA <213> Homo sapiens <400> 735 guugggacaa gaggacgguc uu 22 <210> 736 <211> 21 <212> RNA <213> Homo sapiens <400> 736 aaaaacugca aucacuuuug c 21 <210> 737 <211> 22 <212> RNA <213> Homo sapiens <400> 737 agguggaugc aaugugaccu ca 22 <210> 738 <211> 93 <212> RNA <213> Homo sapiens <400> 738 gugcuuccug cgggcugagc gcgggcugag cgcugccagu cagcgcucac auuaaggcug 60 acagcgcccu gccuggcucg gccggcgaag cuc 93 <210> 739 <211> 87 <212> RNA <213> Homo sapiens <400> 739 ucucagccug ugacccucua gagggaagcg cuuucuguug ucugaaagaa aagaaagugc 60 aucuuuuuag aggauuacag uuugaga 87 <210> 740 <211> 22 <212> RNA <213> Homo sapiens <400> 740 ugcaacuuac cugagucauu ga 22 <210> 741 <211> 22 <212> RNA <213> Homo sapiens <400> 741 cacuguuuca ccacuggcuc uu 22 <210> 742 <211> 91 <212> RNA <213> Homo sapiens <400> 742 uauaacauug uauauaccca cugugauauu aagaguaaua gcucucuagg uuauuaugaa 60 uaauaucaca guagguguac acaauguugu a 91 <210> 743 <211> 127 <212> RNA <213> Homo sapiens <400> 743 cuggagacua agaaaauaga guccuugaaa ucaagcugac ucugcuuuua gccuccuaaa 60 ugaaaaggua gauagaacag gucuuguuug caaaauaaau ucaagaccua cuuaucuacc 120 aacagca 127 <210> 744 <211> 87 <212> RNA <213> Homo sapiens <400> 744 gcccauuugc cuuggcuugg gguggcaguc cugugggaau gagagaugcc aaacuggacc 60 ugccagcccc guuccagggc acagcau 87 <210> 745 <211> 208 <212> RNA <213> Homo sapiens <400> 745 ccaaugugga uacacccagg aggucacucu cuccccaggc uguguccaag uagcauaggg 60 gagcacaggg cucugucccc augauguacu guccuuuucc augacauugg agaugaagcu 120 ggaccucaac ucugcacaug cauauuccua caacuucuca gaguccugug gauaaugacg 180 gaggagagaa accaugcagg aaacagcc 208 <210> 746 <211> 132 <212> RNA <213> Homo sapiens <400> 746 ugagaugaga ucaugccauu gcacuccagc cuggacgaca gagcgagacu ucaucucaaa 60 aaaaaaaaag gauccucagg gcugccaacc uuauaguaga aguugaggug guaguggauu 120 ucuccuacac aa 132 <210> 747 <211> 81 <212> RNA <213> Homo sapiens <400> 747 ccaguuccug aguuuaugca agaugcccau gggagcccag agacguccua uggcgagacu 60 ggcauguacu cacacaacug a 81 <210> 748 <211> 22 <212> RNA <213> Homo sapiens <400> 748 auugccucug uucuaacaca ag 22 <210> 749 <211> 99 <212> RNA <213> Homo sapiens <400> 749 cgcccaccuc agccucccaa aaugcuggga uuacaggcau gagccacugc ggucgaccau 60 gaccuggaca uguuugugcc caguacuguc aguuugcag 99 <210> 750 <211> 77 <212> RNA <213> Homo sapiens <400> 750 auuguuacau ugauaaaauc aaaucaccau cuuuuagcua agcuugugcu ggauuugcuu 60 uuuuucugau aaagaug 77 <210> 751 <211> 22 <212> RNA <213> Homo sapiens <400> 751 gcagagugca aacaauuuug ac 22 <210> 752 <211> 98 <212> RNA <213> Homo sapiens <400> 752 aacauguugu cugugguacc cuacucugga gagugacaau cauguauaau uaaauuugau 60 ugacacuucu gugaguagag uaacgcauga cacguacg 98 <210> 753 <211> 74 <212> RNA <213> Homo sapiens <400> 753 gggugaggua guagguugua uaguuugggg cucugcccug cuaugggaua acuauacaau 60 cuacugucuu uccu 74 <210> 754 <211> 22 <212> RNA <213> Homo sapiens <400> 754 aaagugcauc cuuuuagagu gu 22 <210> 755 <211> 22 <212> RNA <213> Homo sapiens <400> 755 ccgcacugug gguacuugcu gc 22 <210> 756 <211> 94 <212> RNA <213> Homo sapiens <400> 756 uggaucgaug augacuucca uauauacauu ccuuggaaag cugaacaaaa ugagugaaaa 60 cucuauacug ucauccucgu cgaacugagg ucca 94 <210> 757 <211> 22 <212> RNA <213> Homo sapiens <400> 757 ucugugagac caaagaacua cu 22 <210> 758 <211> 77 <212> RNA <213> Homo sapiens <400> 758 uggacaaaug auuagauuag auuguguuau aaaccaaaga uuauaguuau uccaauuaug 60 ugcauuugag auccacu 77 <210> 759 <211> 89 <212> RNA <213> Homo sapiens <400> 759 cuggccucca gggcuuugua caugguaggc uuucauucau ucguuugcac auucggugaa 60 ggucuacugu gugccaggcc cugugccag 89 <210> 760 <211> 22 <212> RNA <213> Homo sapiens <400> 760 gagcuuggau gagcugggcu ga 22 <210> 761 <211> 71 <212> RNA <213> Homo sapiens <400> 761 ucaauaauga aaucuucuga uuuggugaga aauaaugccu uaaaauuaca cucaauagga 60 uuaugcugag g 71 <210> 762 <211> 22 <212> RNA <213> Homo sapiens <400> 762 agacaucaag aucaguccca aa 22 <210> 763 <211> 77 <212> RNA <213> Homo sapiens <400> 763 auuuuggcca acucugaccc cuuagguuga ugucagaaug agguguacca accuaggugg 60 ucagaguugg ccaaaau 77 <210> 764 <211> 20 <212> RNA <213> Homo sapiens <400> 764 aaguccugcu ucuguugcag 20 <210> 765 <211> 17 <212> RNA <213> Homo sapiens <400> 765 auggagaagg cuucuga 17 <210> 766 <211> 22 <212> RNA <213> Homo sapiens <400> 766 aaaaguauuu gcggguuuug uc 22 <210> 767 <211> 20 <212> RNA <213> Homo sapiens <400> 767 ccucugggcc cuuccuccag 20 <210> 768 <211> 22 <212> RNA <213> Homo sapiens <400> 768 ccaaggaagg aggcuggaca uc 22 <210> 769 <211> 68 <212> RNA <213> Homo sapiens <400> 769 gacacuuggg agggaagaca gcuggagagu auggucacag cagcauccuc cucuguuuuc 60 uuuccuag 68 <210> 770 <211> 22 <212> RNA <213> Homo sapiens <400> 770 agggaaggag gcuuggucuu ag 22 <210> 771 <211> 22 <212> RNA <213> Homo sapiens <400> 771 ccagagaugg uugccuuccu au 22 <210> 772 <211> 22 <212> RNA <213> Homo sapiens <400> 772 aucgugcauc ccuuuagagu gu 22 <210> 773 <211> 81 <212> RNA <213> Homo sapiens <400> 773 accugcccug ggcuuucuag ucucagcucu ccugaccagc ugagcuggag gagagcugag 60 acuagaaagc ccagggcagg u 81 <210> 774 <211> 23 <212> RNA <213> Homo sapiens <400> 774 agcagcauug uacagggcua uga 23 <210> 775 <211> 21 <212> RNA <213> Homo sapiens <400> 775 uuggccacaa uggguuagaa c 21 <210> 776 <211> 69 <212> RNA <213> Homo sapiens <400> 776 auguaauaau guucaucaaa ugucugaccu gaaaugagca uguagacaag uuaauuuaac 60 acugaagaa 69 <210> 777 <211> 56 <212> RNA <213> Homo sapiens <400> 777 aaagguaacu gugauuuuug cuauuagaaa guaauggcaa aaacugcaau uacuuu 56 <210> 778 <211> 21 <212> RNA <213> Homo sapiens <400> 778 cgcuuugcuc agccagugua g 21 <210> 779 <211> 101 <212> RNA <213> Homo sapiens <400> 779 aaccaugaau gcaagaagcg uaugauuggg uuuucaugcu cacgugugaa auggaccacc 60 cucaaaccug guuaugcuau cagcacauua ccugucugau g 101 <210> 780 <211> 134 <212> RNA <213> Homo sapiens <400> 780 acucucucgg cucugcauag uugcacuugg cuucacccgu gugacuuucg uaacggggag 60 agagagaaaa gaucuccuca ggaccucgga ugggccuuac uguggccucu cuuuccuuga 120 ggggugcaac aggc 134 <210> 781 <211> 22 <212> RNA <213> Homo sapiens <400> 781 uggaauguaa ggaagugugu gg 22 <210> 782 <211> 85 <212> RNA <213> Homo sapiens <400> 782 auuacagaca ugagcgacug ugccugacca aaagucaaca uuaaacaaca aaucuuggcc 60 aggcacagug gcucaugccu guaau 85 <210> 783 <211> 22 <212> RNA <213> Homo sapiens <400> 783 ccucugaaau ucaguucuuc ag 22 <210> 784 <211> 104 <212> RNA <213> Homo sapiens <400> 784 aucauuuugc agcuuauaca ugugaugacu ggguuuuuua acucauaagu gagaugugcc 60 uuucuuacau cuuauuauga cauuaguaca uuacccauuu gaua 104 <210> 785 <211> 88 <212> RNA <213> Homo sapiens <400> 785 ucccaugcug ugacccucca aagggaagcg cuuucuguuu guuuucucuu aaacaaagug 60 ccucccuuua gaguguuacc guuuggga 88 <210> 786 <211> 92 <212> RNA <213> Homo sapiens <400> 786 agaucauuga ugacuuccau auauccauuc cuuggaaagc ugaacaacau gagugaaaac 60 ucuacugaaa aaagaaaaga aaugggaggc cg 92 <210> 787 <211> 22 <212> RNA <213> Homo sapiens <400> 787 uaauacuguc ugguaaaacc gu 22 <210> 788 <211> 77 <212> RNA <213> Homo sapiens <400> 788 ccucacuuau cugacucuga aaucuucuaa augguaccca cuuuauuuag aacguuuuag 60 ggucaaauaa guacagg 77 <210> 789 <211> 23 <212> RNA <213> Homo sapiens <400> 789 ucaaggccag aggucccaca gca 23 <210> 790 <211> 22 <212> RNA <213> Homo sapiens <400> 790 ucgggcgcaa gagcacugca gu 22 <210> 791 <211> 82 <212> RNA <213> Homo sapiens <400> 791 ggguguacac ccccugcgac auuggaagua guaucaucuc ucccuuggau gcuacgaaca 60 auaucacaga agguguacac cc 82 <210> 792 <211> 22 <212> RNA <213> Homo sapiens <400> 792 aggacuggac ucccggcagc cc 22 <210> 793 <211> 22 <212> RNA <213> Homo sapiens <400> 793 agaggcugag aaggugaugu ug 22 <210> 794 <211> 76 <212> RNA <213> Homo sapiens <400> 794 caaauacaug augaucucac cucaguuuga acucucucac ugaucacuug augacaauaa 60 aagaucugau auugug 76 <210> 795 <211> 133 <212> RNA <213> Homo sapiens <400> 795 acugccccua gaggcguugc agcuguggcu gccgugucac aucuguguca uuagguggca 60 gagauuagag aggcuauguc uacgcucagc guucugcccc gugaacguuu gaauguuuga 120 uagucucaca cuc 133 <210> 796 <211> 134 <212> RNA <213> Homo sapiens <400> 796 gucugcauuu gaaagugauc aucagcuagc cugugucuuc gucaucgaua guacaggccg 60 gugaacugcg caaagcauuu ucugcauuug gaggguccau cucuauccuu ggaaaugcua 120 gugcuuuucu caca 134 <210> 797 <211> 73 <212> RNA <213> Homo sapiens <400> 797 aaaauggagc uggccaaaaa gcaggcagag acuuuaaaag cgucucugcc ugcuuuuugg 60 ccagcuccgu uuu 73 <210> 798 <211> 82 <212> RNA <213> Homo sapiens <400> 798 cagucagugu cgagaaccuu auauuguucu gaagagaggu ggugacuuaa aaaucaugcu 60 caauaggauu acgcugaggc cc 82 <210> 799 <211> 112 <212> RNA <213> Homo sapiens <400> 799 agacgaggag uuaagaguuc auucggcugu ccagauguau ccaaguaccc uguguuauuu 60 ggcaauaaau acaucugggc aacugacuga acuuuucacu uuucaugacu ca 112 <210> 800 <211> 19 <212> RNA <213> Homo sapiens <400> 800 accgugcaaa gguagcaua 19 <210> 801 <211> 101 <212> RNA <213> Homo sapiens <400> 801 auccuuuugu aagucauaag ugugauuggg uuuucaugcu cuugugucaa augugccucc 60 cucaaaccuu guuacgaagu gggcacacua cccaccugau g 101 <210> 802 <211> 71 <212> RNA <213> Homo sapiens <400> 802 aagaucaaug augacuacug uuaguguaug aguuacacau gaugaauaca ugucugaaac 60 ucugaggucc a 71 <210> 803 <211> 67 <212> RNA <213> Homo sapiens <400> 803 uggaaaagag aggagcagug gugcuguggc aguggcagag gucgcuacag cccugugauc 60 uuuccag 67 <210> 804 <211> 105 <212> RNA <213> Homo sapiens <400> 804 aacauuuaaa aaaauguauc aaggcguggu gauuagguuu ucacacucau gugugagaug 60 ugccucccuu gaacuuuguu acauuggcac uuuacccauu ugaca 105 <210> 805 <211> 22 <212> RNA <213> Homo sapiens <400> 805 ugagguagua aguuguauug uu 22 <210> 806 <211> 93 <212> RNA <213> Homo sapiens <400> 806 aucuacaaug gugaugggug aauuuguaga aggaugaaag ucaaagaauc cuucugggaa 60 cuaauuuuug gccuucaaca agaauuguga uau 93 <210> 807 <211> 63 <212> RNA <213> Homo sapiens <400> 807 gugcauguga ugaagcaaau caguaugaau gaauucauga uacuguaaac gcuuucugau 60 gua 63 <210> 808 <211> 107 <212> RNA <213> Homo sapiens <400> 808 agaagaugcu uacuacuagg uuggugcaaa aguaauugug guuuuugcau uuaaaguaau 60 ggccaaaacc gcgauuacuc uugcacgaac cuaacgguaa cacuucu 107 <210> 809 <211> 89 <212> RNA <213> Homo sapiens <400> 809 acgcgccuga ugcggaccug gguuagcgga gugaggccca guggucaccg ccgcccuccg 60 cagguccagg uugccgugcg caugugccu 89 <210> 810 <211> 91 <212> RNA <213> Homo sapiens <400> 810 uuuucaaagc aaugugugac agguacaggg acaaaucccg uuaauaagua agaggauuug 60 ugcuuggcuc ugucacaugc cacuuugaaa a 91 <210> 811 <211> 86 <212> RNA <213> Homo sapiens <400> 811 uggggcccug gcugggauau caucauauac uguaaguuug cgaugagaca cuacaguaua 60 gaugauguac uaguccgggc accccc 86 <210> 812 <211> 216 <212> RNA <213> Homo sapiens <400> 812 aagauuauau uuccaggggu cauuucugug guucauuacu uaaaggaguu uccccaagug 60 uguagagcac uggaaaccac aggaagauau gcaauguucu cucccgagca cgaagcucgu 120 ucuugguguu gcuucauugc aacugccauu ugccauugau cauuguuuuu uucuuccuuu 180 ggggagauua agaggaagag gacacagucu gaguga 216 <210> 813 <211> 77 <212> RNA <213> Homo sapiens <400> 813 ucacuuuggu gccuaggcug agacugcagu ggugcaaucu caguucacug cagccuugac 60 cuccugggcu cagguga 77 <210> 814 <211> 135 <212> RNA <213> Homo sapiens <400> 814 cuccaugugu cuuuggaacc ugucagcugu ggcaguugcc cuuccuagcc auggaagagu 60 aaguauauuc uuguuuauug gcaaagcugu caccauuuca uugguaucag auucugacuu 120 gcacaaguaa cauuc 135 <210> 815 <211> 104 <212> RNA <213> Homo sapiens <400> 815 auccuuuuga aguucauaag cauggugauu ggguuuucac acucaugugu gagauguacc 60 acccuuaaag cuuguuauga uguaggcaca uuacccaucu gaca 104 <210> 816 <211> 82 <212> RNA <213> Homo sapiens <400> 816 ugagcuguug gauucggggc cguagcacug ucugagaggu uuacauuucu cacagugaac 60 cggucucuuu uucagcugcu uc 82 <210> 817 <211> 278 <212> RNA <213> Homo sapiens <400> 817 aggucgauga ugauugguaa aaggucugau ugcacugaau gucacggucc cuuuguugcc 60 cucaacuccc agcagcccau uuuuucccuc ccgucacauu uaagucaugu guaugggauc 120 auggagcagc ugauaauuug ggauucuguc aguguguguu ucugagagug aucggcucac 180 agcugacgag uauccaacaa aaccaguuac acaggagacu gacgaguggc agucaugggu 240 gugauggugc augaucucaa guuuucaauc ugagaccu 278 <210> 818 <211> 84 <212> RNA <213> Homo sapiens <400> 818 gcaucuugca gagccguucc aaugcgacac cucuagagug ucauccccua gaaugucacc 60<and= uuggaaagac ucugcaagau gccu 84 <210> 819 <211> 96 <212> RNA <213> Homo sapiens <400> 819 gguauuguua gauuaauuuu gugggacauu aacaacagca ucagaagcaa caucagcuuu 60 aguuaaugaa uccuggaaag uuaagugacu uuauuu 96 <210> 820 <211> 22 <212> RNA <213> Homo sapiens <400> 820 uaugcauugu auuuuuaggu cc 22 <210> 821 <211> 22 <212> RNA <213> Homo sapiens <400> 821 ugaaguuaca ucauggucgc uu 22 <210> 822 <211> 127 <212> RNA <213> Homo sapiens <400> 822 gacuucucac ugagcuucuu ucugucuguu gcuggcagcu uauggauuca uaugagcaga 60 gagaaucaca gaacuagcau uacuuuuguc uuuacaggag uauauuuggc ugucuuguga 120 gauauua 127 <210> 823 <211> 69 <212> RNA <213> Homo sapiens <400> 823 ugguucagug uugacuacug gugucgugug agucauacaa ugaauacaug ucuggaacuc 60 ugaggccca 69 <210> 824 <211> 114 <212> RNA <213> Homo sapiens <400> 824 auccuuuugc gguucauaaa gaaccaagau gacuggguuu caugcuaaug caugacaugu 60 gccucccuca aaucauguug ccucaugggc uuauuggcac auuaccgucu gagg 114 <210> 825 <211> 18 <212> RNA <213> Homo sapiens <400> 825 gguggggggu guuguuuu 18 <210> 826 <211> 22 <212> RNA <213> Homo sapiens <400> 826 ugcuggcuca uuucauaugu gu 22 <210> 827 <211> 22 <212> RNA <213> Homo sapiens <400> 827 caaaaguaau uguggauuuu gu 22 <210> 828 <211> 72 <212> RNA <213> Homo sapiens <400> 828 guguuuaggg uacucagagc aaguugugaa acacaggugu uuuuuaaccu caccuugcau 60 cugcaucccc ag 72 <210> 829 <211> 53 <212> RNA <213> Homo sapiens <400> 829 ucacuuuagg agaaguaaag uagaacuuug guuuucaacu uuuccuacag ugu 53 <210> 830 <211> 115 <212> RNA <213> Homo sapiens <400> 830 gugccuaagg uuaacacagc gccuuaagag gcuaacacag aagggcaaag uaagucucca 60 uaaaacccag agaagacugu gaaccccucu cuggauccug ucuggaguca cagcu 115 <210> 831 <211> 68 <212> RNA <213> Homo sapiens <400> 831 ccucauugau uaguagcuuc ugacuuuugu ucugaguuug cugaagcuag augccauucc 60 [[ID= <210> 832 <211> 22 <212> RNA <213> Homo sapiens <400> 832 ugggagagca ggguauugug ga 22 <210> 833 <211> 65 <212> RNA <213> Homo sapiens <400> 833 guucaugaua aguaacauuu cuucaauuug accugaugug uauugaagaa aaccagcauc 60 ugagg 65 <210> 834 <211> 22 <212> RNA <213> Homo sapiens <400> 834 cgucuuaccc agcaguguuu gg 22 <210> 835 <211> 23 <212> RNA <213> Homo sapiens <400> 835 uauggagugg acuuucagcu ggc 23 <210> 836 <211> 76 <212> RNA <213> Homo sapiens <400> 836 gggucaauga ugagauguua ccuugaagag aaaugaugac guaaaaauua aguucaguug 60 gauuacgcug aggccc 76 <210> 837 <211> 64 <212> RNA <213> Homo sapiens <400> 837 gagcucuggg aggggcuggg uuuggcagga caguuuccaa gcccugucuc cucccaucuu 60 ccag 64 <210> 838 <211> 19 <212> RNA <213> Homo sapiens <400> 838 uugccauguc uaagaagaa 19 <210> 839 <211> 80 <212> RNA <213> Homo sapiens <400> 839 ugagaggccg caccuugccu ugcugcccgg gccgugcacc cgugggcccc agggcgacgc 60 ggcgggggcg gcccuagcga 80 <210> 840 <211> 99 <212> RNA <213> Homo sapiens <400> 840 uuuagcgguu ucucccugaa gugaugugua acugaucagg aucuacucau gucgucuuug 60 guaaaguuau gucgcuuguc agggugagga gaguuuuug 99

Claims

1. Use of a probe in preparing a kit for screening a subject at risk of developing prostate cancer, the use comprising: (i) detecting an aggregated expression profile of a signature set of cDNAs derived from total small non-coding RNAs (sncRNAs) from a biological sample obtained from said subject, wherein detecting the aggregate expression profile of the characteristic set of sncRNAs comprises hybridizing a probe specific for each cDNA of the sncRNAs derived from the biological sample, The nucleotide sequence of the probe is shown in SEQ ID NO: 1-280; (ii) by comparing the aggregated expression profiles of SEQ ID NOs: 1-280 in a training dataset from a target population without prostate cancer and a training dataset from a target population with prostate cancer, correlating said aggregated expression profile of SEQ ID NOs: 1-280 from said biological sample; and (iii) determining the likelihood that the subject has a risk of developing prostate cancer based on the results obtained from (ii) above.

2. The method of claim 1 , wherein the expression of sncRNA in subjects at risk of developing prostate cancer is reanalyzed and compared with the clustered expression profiles of SEQ ID NOs: 281-560 in a training dataset of a target population with low-grade, indolent prostate cancer of GG1 and a training dataset of a target population with intermediate / high-grade prostate cancer of GG2-GG5 to further classify the subjects as having low-grade, indolent prostate cancer of GG1 or intermediate / high-grade prostate cancer of GG2-GG5.

3. The use according to claim 2, wherein the expression of sncRNA in subjects with intermediate / high grade aggressive prostate cancer of GG2-GG5 is reanalyzed and compared with the clustered expression profile of SEQ ID NO: 561-840 in a training set from a target population with low / intermediate grade prostate cancer of GG1-GG2 or high grade aggressive prostate cancer of GG3-GG5 to further classify the subjects as having low / intermediate grade prostate cancer of GG1-GG2 or high grade aggressive prostate cancer of GG3-GG5.

4. The use according to claim 3, wherein the subject classified as having intermediate / high grade prostate cancer of GG2-GG5 is treated with one or more of radical prostatectomy, prostate radiotherapy and adjuvant hormonal therapy.

5. The use according to claim 3, wherein the subject classified as having intermediate / high grade prostate cancer of GG2-GG5 is treated with prostate brachytherapy or neoadjuvant hormone therapy. The use according to claim 1 , wherein the biological sample is cell-free urine. The use according to claim 1 , wherein the biological sample is urinary exosomes.

8. The method according to claim 1, wherein the biological sample is sncRNA extracted from urinary exosomes.

9. The method according to claim 1, wherein the sncRNA comprises miRNA, C / D box snoRNA, H / ACA box snoRNA, scaRNA, piRNA and lncRNA.

10. The use according to claim 1, wherein the sncRNA comprises miRNA and snoRNA.

11. The method of claim 1, wherein screening a subject at risk for prostate cancer comprises performing a Sentinel TM PCa testing, wherein the PCa testing comprises the following steps: (i) interrogating the sncRNA sequences of SEQ ID NOs: 1-280 on an open array platform to obtain informative sequences; (ii) determining a PCa score that examines the aggregate expression profiles of all sequences included in the first classification algorithm and the interactions between sequences; (iii) comparing the PCa score of the informative sequence described in (ii) with the PCa score obtained from a training dataset of subjects known to have prostate cancer or a training dataset of subjects known not to have prostate cancer; and (iv) determining whether the subject has prostate cancer or does not have prostate cancer.

12. The method of claim 11, wherein screening a subject for prostate cancer comprises classifying the subject as having low-grade, indolent prostate cancer of GG1 or intermediate / high-grade prostate cancer of GG2-GG5, comprising performing a Sentinel TM CS test, wherein the CS test comprises the following steps: (i) interrogating the sncRNAs of SEQ ID NOs: 281-560 in a second round on an open array platform to obtain a different set of informative sequences; (ii) determining a CS score that examines the aggregate expression profiles of all sequences included in the second classification algorithm and the interactions between sequences; (iii) comparing the CS score of the information sequence described in (ii) with the CS scores obtained from a training dataset of men with known GG1 low-grade prostate cancer and a training dataset of another group of men with known GG2-GG5 intermediate / high-grade prostate cancer; and (iv) Determining whether the subject has low-grade prostate cancer of GG1 or intermediate / high-grade prostate cancer of GG2-GG5.

13. The method of claim 12, wherein screening a subject for prostate cancer comprises classifying the subject as having low-grade / favorable intermediate-grade prostate cancer of GG1-GG2 or unfavorable intermediate-grade / high-grade prostate cancer of GG2-GG5, further comprising performing a Sentinel TM HG test, wherein the HG test comprises the following steps: (i) interrogating the sncRNAs of SEQ ID NOs: 561-840 in the third round on an open array platform to obtain different informative sequence sets; (ii) determining an HG score that examines the aggregate expression profiles of all sequences included in the third classification algorithm and the interactions between sequences; (iii) comparing the HG score of the informative sequence described in (ii) with the HG scores obtained from a training dataset of patients with low-grade / favorable intermediate-grade prostate cancer of GG1-GG2 and unfavorable intermediate-grade / high-grade prostate cancer of GG3-GG5; and (iv) Determining whether the subject has low-grade / favorable intermediate-grade prostate cancer of GG1-GG2 or unfavorable intermediate-grade / high-grade prostate cancer of GG3-GG-5.

14. The method according to claim 1, wherein the step of detecting comprises microarray, polymerase chain reaction, nucleic acid hybridization or a combination thereof.

15. The use according to claim 14, wherein the step of detecting comprises reverse transcription polymerase chain reaction.

16. The use according to claim 1, wherein the clustered expression profile of the signature set of sncRNAs in a subject at risk of prostate cancer is a combination of higher or lower clustered expression profiles of the signature set of sncRNAs compared to the clustered expression profile of the signature set of sncRNAs in a subject not suffering from prostate cancer, and the nucleotide sequence of the sncRNAs is shown in SEQ ID NOs: 1-280.

17. The use according to claim 1, wherein the clustered expression profile of the signature set of sncRNAs in subjects with intermediate / high grade prostate cancer of GG2-GG5 is a combination of higher or lower clustered expression profiles of the signature set of sncRNAs compared to the clustered expression profile of the signature set of sncRNAs in subjects with low grade, indolent prostate cancer of GG1, the nucleotide sequences of the sncRNAs being shown as SEQ ID NOs: 281-560.

18. Use of a probe in preparing a kit for diagnosing prostate cancer in a subject, the use comprising: (i) detecting an aggregated expression profile of a signature set of cDNAs derived from total small non-coding RNAs (sncRNAs) from a biological sample obtained from said subject, wherein detecting the aggregated expression profile of the signature set of sncRNAs comprises hybridizing a probe specific for each cDNA derived from the sncRNA obtained from the biological sample, The nucleotide sequence of the probe is shown in SEQ.ID.NO: 1-280; (ii) correlating the aggregated expression profile of SEQ ID NOs: 1-280 from the biological sample by comparing the aggregated expression profile of SEQ ID NOs: 1-280 in a training dataset from a target population without prostate cancer and a training dataset from a target population with prostate cancer; and (iii) determining the possibility that the subject is at risk of developing prostate cancer based on the results obtained in (ii) above sex.

19. The use according to claim 18, wherein the sncRNA expression of the subject determined to be at risk for prostate cancer is reanalyzed and compared with the clustered expression profiles of SEQ ID NO: 281-560 in a training dataset from a target population with indolent or aggressive prostate cancer to further classify the subject as having low-grade indolent prostate cancer of GG1 or intermediate / high-grade prostate cancer of GG2-GG5.

20. The use according to claim 19, wherein the sncRNA expression of the subject determined to be at risk for intermediate / high grade prostate cancer of GG2-GG5 is reanalyzed and compared with the clustered expression profiles of SEQ ID NO: 561-840 in a training dataset of a target population with low / intermediate grade prostate cancer of GG1-GG2 and a training dataset of a target population with high grade prostate cancer of GG3-GG5 to further classify the subject as having low / intermediate grade prostate cancer of GG1-GG2 or high grade aggressive prostate cancer of GG3-GG5.

21. The use according to claim 18 or 19, wherein the subject classified as having intermediate / high grade prostate cancer of GG3-GG5 is treated with one or more of radical prostatectomy, prostate radiotherapy and adjuvant hormonal therapy.

22. The use according to claim 18 or 19, wherein the subject classified as having intermediate / high grade prostate cancer GG3-GG5 is treated with prostate brachytherapy or neoadjuvant hormonal therapy.

23. The use according to claim 18, wherein the biological sample is cell-free urine.

24. The use according to claim 18, wherein the biological sample is urinary exosomes.

25. The use according to claim 18, wherein the biological sample is sncRNA extracted from urinary exosomes. The use according to claim 18 , wherein the sncRNA comprises miRNA, C / D box snoRNA, H / ACA box snoRNA, scaRNA, piRNA and lncRNA.

27. The use according to claim 18, wherein the sncRNA comprises miRNA and snoRNA.

28. The use according to claim 18, further comprising analyzing whether the aggregated expression profile of the signature set of sncRNAs is higher or lower than the aggregated expression level of the signature set of sncRNAs in an inert prostate biological sample.

29. The method of claim 18, wherein diagnosing a subject at risk for prostate cancer comprises performing a Sentinel TM PCa testing.

30. The use of claim 19, wherein diagnosing the subject as having indolent / low-grade prostate cancer of GG1 or intermediate / high-grade prostate cancer of GG2-GG5 comprises performing a Sentinel TM CS test.

31. The method of claim 20, wherein the subject is diagnosed with low / intermediate grade prostate cancer of GG-1-GG2 or high grade prostate cancer of GG3-GG5, comprising performing a Sentinel TM HG test.

32. The use according to claim 18, wherein the step of diagnosing comprises microarray, polymerase chain reaction, nucleic acid hybridization or a combination thereof.

33. The use according to claim 32, wherein the step of detecting comprises reverse transcription polymerase chain reaction.

Citation Information

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