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Patent Analysis of

MiRNA fingerprint in the diagnosis of multiple sclerosis

Updated Time 12 June 2019

Patent Registration Data

Publication Number

US10000810

Application Number

US14/873385

Application Date

02 October 2015

Publication Date

19 June 2018

Current Assignee

HUMMINGBIRD DIAGNOSTICS GMBH

Original Assignee (Applicant)

COMPREHENSIVE BIOMARKER CENTER GMBH

International Classification

C12Q1/68,G06F19/20,G06F19/24

Cooperative Classification

C12Q1/6883,C12Q1/6809,C12Q1/6886,G06F19/20,G06F19/24

Inventor

KELLER, ANDREAS,MEESE, ECKART,BORRIES, ANNE,STAEHLER, PEER FRIEDRICH,BEIER, MARKUS

Patent Images

This patent contains figures and images illustrating the invention and its embodiment.

US10000810 MiRNA fingerprint diagnosis 1 US10000810 MiRNA fingerprint diagnosis 2 US10000810 MiRNA fingerprint diagnosis 3
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Abstract

The present invention provides novel methods for diagnosing diseases based on the determination of specific miRNAs that have altered expression levels in disease states compared to healthy controls.

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Claims

1. A method of diagnosing multiple sclerosis, comprising(a) obtaining blood cells from a blood sample from a patient suspected of having multiple sclerosis, wherein said blood cells consists of a mixture of erythrocytes, leukocytes and thrombocytes,(b) extracting total RNA from said mixture of blood cells,(c) determining an expression profile of a predetermined set of miRNAs in said total RNA, said predetermined set of miRNAs comprising one or more miRNAs is selected from the group consisting of hsa-miR-20b, hsa-miR-145, hsa-miR-186, hsa-miR-664, hsa-miR-584, hsa-miR-223, hsa-miR-422a, hsa-miR-142-3p, and hsa-let-7c, wherein determining said expression profile comprises nucleic acid amplification performed using real-time PCR (RT-PCR), and(d) comparing said expression profile to a reference expression profile, wherein said reference expression profile is obtained using a mixture of erythrocytes, leukocytes and thrombocytes from healthy subjects, wherein the comparison of said determined expression profile to said reference expression profile allows for the diagnosis of multiple sclerosis.

2. The method of claim 1, wherein said predetermined set of miRNAs comprises hsa-miR-20b (SEQ ID NO: 11).

3. The method of claim 1, wherein the diagnosis comprises determining survival rate, responsiveness to drugs, and/or monitoring the course of the disease or the therapy, staging of the disease, measuring the response of a patient to therapeutic intervention, segmentation of patients suffering from the disease, identifying of a patient who has a risk to develop the disease, predicting/estimating the occurrence, predicting/estimating the severity of the occurrence of the disease, or predicting the response of a patient with the disease to therapeutic intervention.

4. The method of claim 1, wherein the determination of an expression profile in step (c) comprises qualitative, quantitative or semiquantitative determination of said predetermined set of miRNAs.

5. The method of claim 1, wherein said predetermined set of miRNAs further comprises hsa-miR-186.

6. The method of claim 1, wherein said predetermined set of miRNA comprises at least one miRNA molecule or signature of miRNA molecules as shown in Table 1.

7. The method of claim 5, wherein said predetermined set of miRNAs comprises a signature selected from the group consisting of A29: hsa-miR-20a*, hsa-miR-646, hsa-miR-885-3p, hsa-miR-509-3-5p, hsa-miR-1912 and hsa-miR-20b A30: hsa-miR-509-3-5p, hsa-miR-1912, hsa-miR-20b, hsa-miR-574-5p, hsa-miR-221 and hsa-miR-365 A37: hsa-miR-20a*, hsa-miR-646, hsa-miR-885-3p, hsa-miR-509-3-5p, hsa-miR-1912, hsa-miR-20b, hsa-miR-574-5p, hsa-miR-221, hsa-miR-365 and hsa-miR-22* A38: hsa-miR-20b, hsa-miR-574-5p, hsa-miR-221, hsa-miR-365, hsa-miR-22*, hsa-miR-1275, hsa-miR-625, hsa-miR-584, hsa-miR-328 and hsa-miR-629.

8. The method of claim 1, wherein said predetermined set of miRNAs comprises at least 7, 10, 15 or 20, and/or all of the indicated miRNAs, particularly at least 1, 7, 10, 15, 20, 25, 30, 35, 40, 50, 75, 100 of the miRNAs selected from the group consisting of:(I) the first 193 miRNAs from FIG. 10A,(ii) the first 165 miRNAs from FIG. 10B, and(iii) the 308 miRNAs from FIG. 10C optionally except hsa-miR-148a, hsa-miR-18b, hsa-miR-96, hsa-miR-599, hsa-miR-493, hsa-miR-184, hsa-miR193a.

9. The method of claim 8, wherein said predetermined set of miRNAs comprises the miRNAs hsa-miR-145, hsa-miR-186, hsa-miR-664, hsa-miR-584, hsa-miR-20b, hsa-miR-223 and hsa-miR-422a.

10. The method of claim 8, wherein said predetermined set of miRNAs comprises the miRNAs hsa-miR-145, hsa-miR-186, hsa-miR-664, hsa-miR-584, hsa-miR-20b, hsa-miR-223, hsa-miR-422a, hsa-miR-142-3p, hsa-let-7c, and hsa-miR-151-3p.

11. The method of claim 8, wherein said predetermined set of miRNAs comprises the miRNAs hsa-miR-145, hsa-miR-186, hsa-miR-664, hsa-miR-584, hsa-miR-20b, hsa-miR-223, hsa-miR-422a, hsa-miR-142-3p, hsa-let-7c, hsa-miR-151-3p, hsa-miR-491-5p, hsa-miR-942, hsa-miR-361-3p, hsa-miR-22* and hsa-miR-140-5p.

12. The method of claim 8, wherein said predetermined set of miRNAs comprises the miRNAs hsa-miR-145, hsa-miR-186, hsa-miR-664, hsa-miR-584, hsa-miR-20b, hsa-miR-223, hsa-miR-422a, hsa-miR-142-3p, hsa-let-7c, hsa-miR-151-3p, hsa-miR-491-5p, hsa-miR942, hsa-miR-361-3p, hsa-miR-22*, hsa-miR-140-5p, hsa-miR-216a, hsa-miR-1275, hsa-miR-367, hsa-miR-146a, and hsa-miR-598.

13. The method of claim 3, wherein said therapy is chemotherapy.

14. The method of claim 1, wherein determining the expression profile using real-time PCR (RT-PCR), comprises: a) reverse-transcribing the total RNA isolated from the mixture of blood cells into cDNA, and(b) quantifying the cDNA, thereby determining the expression profile of said miRNAs.

15. The method of claim 8, wherein said predetermined set of miRNAs does not include hsa-miR-148a, hsa-miR-18b, hsa-miR-96, hsa-miR-599, hsa-miR-493, hsa-miR-184, or hsa-miR-193a.

16. The method of claim 2, wherein the severity of the occurrence of the disease is predicted/estimated.

17. A method for the assessment of a clinical condition related to multiple sclerosis of a patient comprising the steps:(a) obtaining blood cells from a blood sample from a patient suspected of having multiple sclerosis, wherein said blood cells consists of a mixture of erythrocytes, leukocytes and thrombocytes,(b) extracting total RNA from said mixture of blood cells,(c) determining an expression profile of a predetermined set of miRNAs in said total RNA, said predetermined set of miRNAs comprising one or more miRNAs is selected from the group consisting of hsa-miR-20b, hsa-miR-145, hsa-miR-186, hsa-miR-664, hsa-miR-584, hsa-miR-223, hsa-miR-422a, hsa-miR-142-3p, and hsa-let-7c; wherein determining said expression profile comprises nucleic acid amplification performed using real-time PCR (RT-PCR), and(d) providing a plurality of miRNA reference expression profiles characteristic for a plurality of diseases, wherein said reference expression profiles are obtained using a mixture of erythrocytes, leukocytes and thrombocytes(e) comparing said miRNA expression profile (of step (c)) with said plurality of miRNA reference expression, and(f) assessing the clinical condition of the patient based on the comparison of step (e).

18. The method of claim 17, wherein said predetermined set of miRNAs comprises hsa-miR-20b (SEQ ID NO: 11).

19. The method of claim 17, wherein said miRNA reference expression profiles in step (d) are obtained from a database such as an internet database, a centralized or a decentralized database.

20. The method of claim 17, wherein the plurality of reference expression profiles comprise one or more miRNAs that are highly deregulated in said diseases as compared to a healthy condition, and/or said miRNAs are strongly increased or decreased in said diseases as compared to a healthy condition.

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Claim Tree

  • 1
    1. A method of diagnosing multiple sclerosis, comprising
    • (a) obtaining blood cells from a blood sample from a patient suspected of having multiple sclerosis, wherein said blood cells consists of a mixture of erythrocytes, leukocytes and thrombocytes,
    • (b) extracting total RNA from said mixture of blood cells,
    • (c) determining an expression profile of a predetermined set of miRNAs in said total RNA, said predetermined set of miRNAs comprising one or more miRNAs is selected from the group consisting of hsa-miR-20b, hsa-miR-145, hsa-miR-186, hsa-miR-664, hsa-miR-584, hsa-miR-223, hsa-miR-422a, hsa-miR-142-3p, and hsa-let-7c, wherein determining said expression profile comprises nucleic acid amplification performed using real-time PCR (RT-PCR), and
    • (d) comparing said expression profile to a reference expression profile, wherein said reference expression profile is obtained using a mixture of erythrocytes, leukocytes and thrombocytes from healthy subjects, wherein the comparison of said determined expression profile to said reference expression profile allows for the diagnosis of multiple sclerosis.
    • 2. The method of claim 1, wherein
      • said predetermined set of miRNAs comprises
    • 3. The method of claim 1, wherein
      • the diagnosis comprises
    • 4. The method of claim 1, wherein
      • the determination of an expression profile in step (c) comprises
    • 5. The method of claim 1, wherein
      • said predetermined set of miRNAs further comprises
    • 6. The method of claim 1, wherein
      • said predetermined set of miRNA comprises
    • 8. The method of claim 1, wherein
      • said predetermined set of miRNAs comprises
    • 14. The method of claim 1, wherein
      • determining the expression profile using real-time PCR (RT-PCR), comprises:
  • 17
    17. A method for the assessment of a clinical condition related to multiple sclerosis of a patient comprising the steps:
    • (a) obtaining blood cells from a blood sample from a patient suspected of having multiple sclerosis, wherein said blood cells consists of a mixture of erythrocytes, leukocytes and thrombocytes,
    • (b) extracting total RNA from said mixture of blood cells,
    • (c) determining an expression profile of a predetermined set of miRNAs in said total RNA, said predetermined set of miRNAs comprising one or more miRNAs is selected from the group consisting of hsa-miR-20b, hsa-miR-145, hsa-miR-186, hsa-miR-664, hsa-miR-584, hsa-miR-223, hsa-miR-422a, hsa-miR-142-3p, and hsa-let-7c; wherein determining said expression profile comprises nucleic acid amplification performed using real-time PCR (RT-PCR), and
    • (d) providing a plurality of miRNA reference expression profiles characteristic for a plurality of diseases, wherein said reference expression profiles are obtained using a mixture of erythrocytes, leukocytes and thrombocytes
    • (e) comparing said miRNA expression profile (of step (c)) with said plurality of miRNA reference expression, and
    • (f) assessing the clinical condition of the patient based on the comparison of step (e).
    • 18. The method of claim 17, wherein
      • said predetermined set of miRNAs comprises
    • 19. The method of claim 17, wherein
      • said miRNA reference expression profiles in step (d) are obtained from a database such as an internet database, a centralized or a decentralized database.
    • 20. The method of claim 17, wherein
      • the plurality of reference expression profiles comprise
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Description

BACKGROUND OF THE INVENTION

MicroRNAs (miRNA) are a recently discovered class of small non-coding RNAs (17-14 nucleotides). Due to their function as regulators of gene expression they play a critical role both in physiological and in pathological processes, such as cancer (Calin and Croce 2006; Esquela-Kerscher and Slack 2006; Zhang, Pan et al. 2007; Sassen, Miska et al. 2008).

There is increasing evidence that miRNAs are not only found in tissues but also in human blood both as free circulating nucleic acids (also called circulating miRNAs) and in mononuclear cells. A recent proof-of-principle study demonstrated miRNA expression pattern in pooled blood sera and pooled blood cells, both in healthy individuals and in cancer patients including patients with lung cancer (Chen, Ba et al. 2008). In addition, a remarkable stability of miRNAs in human sera was recently demonstrated (Chen, Ba et al. 2008; Gilad, Meiri et al. 2008). These findings make miRNA a potential tool for diagnostics for various types of diseases based on blood analysis.

Multiple sclerosis (MS), also known as disseminated sclerosis or encephalomyelitis disseminata) is an inflammatory autoimmune disease of the central nervous system (CNS). Causing MS appears to be a combination of immunological, genetic and environmental factors. It is a chronic demyelinating disease, which primarily affects young adults and is characterized by a highly variable course. The heterogeneous presentation of MS is characterized by a variety of clinical problems arising from multiple regions of demyelination and inflammation along axonal pathways. The signs and symptoms of MS are determined by the location of the affected regions.

Mostly, the disease begins in the third or fourth decade of life. Its initial course is characterized by acute episodes of neurological dysfunction, such as decreased vision, followed by subsequent recovery. This course is known as relapsing-remitting MS. Over time, the improvement after attacks may be incomplete and the relapsing-remitting course may evolve into one of increasing progression of disability, termed secondary progressive MS.

The diagnosis of MS generally relies on the presence of a neurological problem that remits and then returns at an unrelated site. This is confirmed by magnetic resonance imaging (MRI) or functional evidence of lesions in a particular pathway by abnormal evoked potentials. The histological hallmark of MS at postmortem exam is multiple lesions at different sites showing loss of myelin and infiltration by a characteristic complement of inflammatory cells.

The key to identifying predictive markers is a deeper understanding of the factors that underlie the therapeutic response. Identification of biomarkers will in turn allow for stratification of MS patients for their response to a specific treatment, ultimately leading to improved therapeutic benefits and a personalized treatment approach for MS patients.

Identification of reliable biomarkers in MS sclerosis patients bears the potential for an improved MS diagnosis, monitoring the disease activity and progression and also to evaluate response to treatments. The field of biomarker discovery has gradually shifted from the aim to find the perfect surrogate marker to the construction of composite markers with higher performances, taking advantage of technologies allowing unbiased screening, including microarray analyses. However, suitable biomarker sets allowing for a non-invasive diagnosis of MS based on peripheral profiles have not been detected, so far.

Various markers have been proposed to indicate specific types of disorders such as cancer or MS. However, there is still a need for more efficient and effective methods and compositions for the diagnosis of diseases.

SUMMARY OF THE INVENTION

The present invention provides novel methods for diagnosing diseases based on the determination of specific miRNAs that have altered expression levels in disease states compared to healthy or other relevant controls. The present invention particularly provides novel methods for the diagnosis and/or prognosis and/or monitoring of multiple sclerosis or related diseases in human individuals based on miRNA analysis from samples derived from blood.

A first subject-matter of the invention is a method for diagnosing multiple sclerosis, comprising the steps

  • (a) determining an expression profile of a predetermined set of miRNAs in a biological sample from a patient; and
  • (b) comparing said expression profile to a reference expression profile,

    wherein the comparison of said determined expression profile to said reference expression profile allows for the diagnosis of multiple sclerosis.

A “biological sample” in terms of the invention means a sample of biological tissue or fluid. Examples of biological samples are sections of tissues, blood, blood fractions, plasma, serum, etc. A biological sample may be provided by removing a sample of cells from a subject, but can also be provided by using a previously isolated sample. For example, a tissue sample can be removed from a subject suspected of having a disease by conventional biopsy techniques. In a preferred embodiment, a blood sample is taken from the subject. In one embodiment, the blood or tissue sample is obtained from the subject prior to initiation of radiotherapy, chemotherapy or other therapeutic treatment. According to the invention, the biological sample preferably is a blood, plasma, or PBMC (peripheral blood mononuclear cell), or a serum sample. Further, it is also preferred to use blood cells, e.g. erythrocytes, leukocytes or thrombocytes.

A biological sample from a patient means a sample from a subject suspected to be affected by a disease. As used herein, the term “subject” refers to any mammal, including both human and other mammals. Preferably, the methods of the present invention are applied to human subjects.

In step (a) of the method of the invention, an expression profile of a predetermined set of miRNAs is determined. The determination may be carried out by any convenient means for determining nucleic acids. For expression profiling, qualitative, semi-quantitative and preferably quantitative detection methods can be used. A variety of techniques are well known to those of skill in the art. In particular, the determination may comprise nucleic acid hybridization and/or nucleic acid amplification steps.

Nucleic acid hybridization may for example be performed using beads, a solid phase nucleic acid biochip array, in particular a microarray, beads, or in situ hybridization. The miRNA microarray technology affords the analysis of a complex biological sample for all expressed miRNAs. Nucleotides with complementarity to the corresponding miRNAs are spotted, or synthesized on coated carriers. E.g., miRNAs isolated from the sample of interest may be labelled, e.g. fluorescently labelled, so that upon hybridization of the miRNAs to the complementary sequences on the carrier the resulting signal indicates the occurrence of a distinct miRNA. Preferably, microarray methods are employed that do not require labeling of the miRNAs prior to hybridization (FIGS. 3-4) and start directly from total RNA input. On one miRNA microarray, preferably the whole predetermined set of miRNAs can be analyzed. Examples of preferred hybridization assays are shown in FIGS. 1-4. The design of exemplary miRNA capture probes for use in hybridization assays is depicted in FIGS. 5 and 6.

Further, quantitative real-time polymerase chain reaction (RT-PCR) can be used to detect also low abandoned miRNAs. Furthermore, bead-based assays, e.g. the luminex platform, are also suitable.

Furthermore, bead-based assays, e.g. the Luminex platform, are also suited to carry out the present invention.

Alternative methods for obtaining expression profiles may also contain sequencing, next generation sequencing or mass spectroscopy.

The predetermined set of miRNAs in step (a) of the method of the invention depends on the disease to be diagnosed. The inventors found out that single miRNA biomarkers lack sufficient accuracy, specificity and sensitivity, and therefore it is preferred to analyze more complex miRNA expression patterns, so-called miRNA signatures. The predetermined set of miRNAs comprises one or more, preferably a larger number of miRNAs (miRNA signatures) that are differentially regulated in samples of a patient affected by a particular disease compared to healthy or other relevant controls.

The expression profile determined in step (a) is subsequently compared to a reference expression profile or a relevant reference in step (b). This reference may be a mathematical function or algorithm that allows for the diagnosis of the disease. This mathematical function or algorithm has been developed on the basis of a plurality of reference expression profiles. The reference expression profile is the expression profile of the same set of miRNAs in a biological sample originating from the same source as the biological sample from a patient but obtained from a healthy subject. Preferably, both the reference expression profile and the expression profile of step (a) are determined in a blood or serum sample including whole blood, plasma, serum or fractions thereof, or in a sample of peripheral blood mononuclear cells, erythrocytes, leukocytes and/or thrombocytes. It is understood that the reference expression profile is not necessarily obtained from a single healthy subject but may be an average expression profile of a plurality of healthy subjects. It is preferred to use a reference expression profile obtained from a person of the same gender, and a similar age as the patient. It is also understood that the reference expression profile is not necessarily determined for each test. Appropriate reference profiles stored in databases may also be used. These stored references profiles may, e.g., be derived from previous tests. The reference profile may also be a mathematical function or algorithm which is developed on a plurality of measured reference profiles.

The inventors succeeded in developing a generally applicable approach to arrive at miRNA signatures that are correlated with a particular disease. The general work flow is depicted in FIG. 9. In more detail, the following steps are accomplished:

  • 1. miRNAs are extracted from a biological sample of a patient, preferably a blood or serum sample or a sample comprising erythrocytes, leukocytes or thrombocytes, using suitable kits/purification methods
  • 2. The respective samples are measured using experimental techniques. These techniques include but are not restricted to:
    • Array based approaches
    • Real time quantitative polymerase chain reaction
    • Bead based assays (e.g. Luminex)
    • Sequencing
    • Next Generation Sequencing
    • Mass Spectroscopy
  • 3. Mathematical approaches are applied to gather information on the value and the redundancy of single biomarkers. These methods include, but are not restricted to:
    • basic mathematic approaches (e.g. Fold Quotients, Signal to Noise ratios, Correlation)
    • statistical methods as hypothesis tests (e.g. t-test, Wilcoxon-Mann-Whitney test), the Area under the Receiver operator Characteristics Curve
    • Information Theory approaches, (e.g. the Mutual Information, Cross-entropy)
    • Probability theory (e.g. joint and conditional probabilities)
    • Combinations and modifications of the previously mentioned examples
  • 4. The information collected in 3) are used to estimate for each biomarker the diagnostic content or value. Usually, however, this diagnostic value is too small to get a highly accurate diagnosis with accuracy rates, specificities and sensitivities beyond the 90% barrier.
    • Please note that the diagnostic content for our miRNAs can be found in FIGS. 10A, 10B and 10C. This table includes the miRNAs with the sequences, the fold quotient, the mutual information and the significance value as computed by a t-test.
  • 5. Thus statistical learning/machine learning/bioinformatics/computational approaches are applied to define subsets of biomarkers that are tailored for the detection of diseases. These techniques includes but are not restricted to
    • Wrapper subset selection techniques (e.g. forward step-wise, backward step-wise, combinatorial approaches, optimization approaches)
    • Filter subset selection methods (e.g. the methods mentioned in 3)
    • Principal Component Analysis
    • Combinations and modifications of such methods (e.g. hybrid approaches)
  • 6. The diagnostic content of each detected set can be estimated by mathematical and/or computational techniques to define the diagnostic information content of subsets.
  • 7. The subsets, detected in step 5, which may range from only a small number (at least two) to all measured biomarkers is then used to carry out a diagnosis. To this end, statistical learning/machine learning/bioinformatics/computational approaches are applied that include but are not restricted to any type of supervised or unsupervised analysis:
    • Classification techniques (e.g. naïve Bayes, Linear Discriminant Analysis, Quadratic Discriminant Analysis Neural Nets, Tree based approaches, Support Vector Machines, Nearest Neighbour Approaches)
    • Regression techniques (e.g. linear Regression, Multiple Regression, logistic regression, probit regression, ordinal logistic regression ordinal Probit-Regression, Poisson Regression, negative binomial Regression, multinomial logistic Regression, truncated regression)
    • Clustering techniques (e.g. k-means clustering, hierarchical clustering, PCA)
    • Adaptations, extensions, and combinations of the previously mentioned approaches

The inventors surprisingly found out that the described approach yields in miRNA signatures that provide high diagnostic accuracy, specificity and sensitivity in the determination of multiple sclerosis or related disease states/clinical conditions.

According to a preferred embodiment of the invention, the disease to be determined is multiple sclerosis. Surprisingly, the inventors found out that miRNAs are differentially regulated in samples from MS patients as compared to health controls. A complete overview of all miRNAs that are found to be differentially regulated in blood samples of multiple sclerosis patients is provided in the tables shown in FIGS. 10A, 10B and 10C. In one embodiment, 193 miRNAs were found to be significantly deregulated in blood cells of MS patients as compared to controls (FIG. 10A). In a further embodiment—based on additional information—165 miRNAs were found to be significantly deregulated in blood cells of MS patients as compared to controls (FIG. 10B). In a still further embodiment, 308 miRNAs were found to be significantly deregulated in blood cells of MS patients as compared to controls (FIG. 10C).

Preferably, the predetermined set of miRNAs for the diagnosis of multiple sclerosis comprises one or more nucleic acids selected from the deregulated miRNAs presented in the tables in FIG. 10A, 10B or 10C. The predetermined set of miRNAs should preferably comprise at least 7, preferably at least 10, 15, 20 or 24 of the indicated nucleic acids. It is particularly preferred to include the 24, 20, 15, 10 or at least 7 of the first mentioned miRNAs according to their order in the tables in FIG. 10A, 10B or 10C, preferably except hsa-miR-148a, hsa-miR-18b, hsa-miR-96, hsa-miR-96, hsa-miR-599, hsa-miR-493, hsa-miR-184, hsa-miR-193a.

Thus, preferably the predetermined set of miRNAs for the diagnosis of MS comprises one or more nucleic acids selected from the 24 most deregulated miRNAs hsa-miR-145, hsa-miR-186, hsa-miR-664, hsa-miR-584, hsa-miR-20b, hsa-miR-223, hsa-miR-422a, hsa-miR-142-3p, hsa-let-7c, hsa-miR-151-3p, hsa-miR-491-5p, hsa-miR-942, hsa-miR-361-3p, hsa-miR-22*, hsa-miR-140-5p, hsa-miR-216a, hsa-miR-1275, hsa-miR-367, hsa-miR-146a, hsa-miR-598, hsa-miR-613, hsa-miR-18a*, hsa-miR-302b, hsa-miR-501-5p. Preferably, the predetermined set of miRNAs comprises at least 7, preferably at least 10, 15, 20 or all of the above-indicated nucleic acids. Most preferably, the predetermined set of miRNAs comprises those miRNAs that were most significantly deregulated: hsa-miR-145, hsa-miR-186, hsa-miR-664, hsa-miR-584, hsa-miR-20b, hsa-miR-223, hsa-miR-422a, hsa-miR-142-3p, hsa-let-7c.

In another embodiment, the predetermined set of miRNAs for the diagnosis of MS comprises at least one preferred signature 1-84 as shown in Table 1. It should be noted that preferred diagnostic sets may also comprise one or more miRNAs of the miRNAs disclosed in Table 1 and any combination of the miRNAs together with one or more further diagnostically relevant miRNA from FIG. 10A, 10B or 10C. Preferred predetermined sets of miRNA based on Table 1 comprise at least 3, 4, 5, 6, 7, 8, 9 or 10 miRNAs and up to 10, 15, or 20 or more miRNAs.


TABLE 1
Signature
Signature
SEQ-ID Nos
miRNA-identifiers
1
A1
SEQ ID NO: 53, SEQ ID NO: 632, SEQ ID
hsa-let-7b, hsa-miR-574-3p, hsa-miR-500
NO: 526
2
A2
SEQ ID NO: 526, SEQ ID NO: 790, SEQ ID
hsa-miR-500, hsa-miR-1234, hsa-miR-125a-
NO: 806
5p
3
A3
SEQ ID NO: 806, SEQ ID NO: 823, SEQ ID
hsa-miR-125a-5p, hsa-miR-92b*, hsa-let-7c
NO: 15
4
A4
SEQ ID NO: 15, SEQ ID NO: 99, SEQ ID
hsa-let-7c, hsa-miR-145, hsa-miR-330-3p
NO: 641
5
A5
SEQ ID NO: 641, SEQ ID NO: 50, SEQ ID
hsa-miR-330-3p, hsa-miR-30e, hsa-miR-
NO: 75
199a-5p
6
A6
SEQ ID NO: 75, SEQ ID NO: 51, SEQ ID
hsa-miR-199a-5p, hsa-miR-223, hsa-miR-
NO: 13
195
7
A7
SEQ ID NO: 13, SEQ ID NO: 129, SEQ ID
hsa-miR-195, hsa-miR-182, hsa-miR-107
NO: 750
8
A8
SEQ ID NO: 750, SEQ ID NO: 87, SEQ ID
hsa-miR-107, hsa-miR-497, hsa-miR-593*
NO: 137
9
A9
SEQ ID NO: 137, SEQ ID NO: 826, SEQ ID
hsa-miR-593*, hsa-miR-422a, hsa-miR-1301
NO: 778
10
A10
SEQ ID NO: 778, SEQ ID NO: 232, SEQ ID
hsa-miR-1301, hsa-miR-362-5p, hsa-miR-
NO: 644
214
11
A11
SEQ ID NO: 644, SEQ ID NO: 217, SEQ ID
hsa-miR-214, hsa-miR-31*, hsa-miR-24
NO: 358
12
A12
SEQ ID NO: 358, SEQ ID NO: 800, SEQ ID
hsa-miR-24, hsa-miR-146a, hsa-miR-1908
NO: 671
13
A13
SEQ ID NO: 671, SEQ ID NO: 560, SEQ ID
hsa-miR-1908, hsa-miR-103, hsa-miR-106a
NO: 49
14
A14
SEQ ID NO: 560, SEQ ID NO: 274, SEQ ID
hsa-miR-103, hsa-miR-452*, hsa-miR-106a
NO: 49
15
A15
SEQ ID NO: 49, SEQ ID NO: 501, SEQ ID
hsa-miR-106a, hsa-miR-621, hsa-miR-1251
NO: 455
16
A16
SEQ ID NO: 53, SEQ ID NO: 632, SEQ ID
hsa-let-7b, hsa-miR-574-3p, hsa-miR-500,
NO: 526, SEQ ID NO: 790, SEQ ID NO: 806
hsa-miR-1234, hsa-miR-125a-5p
17
A17
SEQ ID NO: 526, SEQ ID NO: 790, SEQ ID
hsa-miR-500, hsa-miR-1234, hsa-miR-125a-
NO: 806, SEQ ID NO: 823, SEQ ID NO: 15
5p, hsa-miR-92b*, hsa-let-7c
18
A18
SEQ ID NO: 806, SEQ ID NO: 823, SEQ ID
hsa-miR-125a-5p, hsa-miR-92b*, hsa-let-7c,
NO: 15, SEQ ID NO: 99, SEQ ID NO: 641
hsa-miR-145, hsa-miR-330-3p
19
A19
SEQ ID NO: 823, SEQ ID NO: 15, SEQ ID
hsa-miR-92b*, hsa-let-7c, hsa-miR-145, hsa-
NO: 99, SEQ ID NO: 641, SEQ ID NO: 50
miR-330-3p, hsa-miR-30e
20
A20
SEQ ID NO: 99, SEQ ID NO: 641, SEQ ID
hsa-miR-145, hsa-miR-330-3p, hsa-miR-30e,
NO: 50, SEQ ID NO: 75, SEQ ID NO: 51
hsa-miR-199a-5p, hsa-miR-223
21
A21
SEQ ID NO: 50, SEQ ID NO: 75, SEQ ID
hsa-miR-30e, hsa-miR-199a-5p, hsa-miR-
NO: 51, SEQ ID NO: 13, SEQ ID NO: 129
223, hsa-miR-195, hsa-miR-182
22
A22
SEQ ID NO: 75, SEQ ID NO: 51, SEQ ID
hsa-miR-199a-5p, hsa-miR-223, hsa-miR-
NO: 13, SEQ ID NO: 129, SEQ ID NO: 750,
195, hsa-miR-182, hsa-miR-107, hsa-miR-
SEQ ID NO: 87
497
23
A23
SEQ ID NO: 129, SEQ ID NO: 750, SEQ ID
hsa-miR-182, hsa-miR-107, hsa-miR-497,
NO: 87, SEQ ID NO: 137, SEQ ID NO: 826,
hsa-miR-593*, hsa-miR-422a, hsa-miR-1301
SEQ ID NO: 778
24
A24
SEQ ID NO: 137, SEQ ID NO: 826, SEQ ID
hsa-miR-593*, hsa-miR-422a, hsa-miR-1301,
NO: 778, SEQ ID NO: 232, SEQ ID NO: 644,
hsa-miR-362-5p, hsa-miR-214, hsa-miR-31*
SEQ ID NO: 217
25
A25
SEQ ID NO: 232, SEQ ID NO: 644, SEQ ID
hsa-miR-362-5p, hsa-miR-214, hsa-miR-31*,
NO: 217, SEQ ID NO: 358, SEQ ID NO: 800,
hsa-miR-24, hsa-miR-146a, hsa-miR-1908
SEQ ID NO: 671
26
A26
SEQ ID NO: 358, SEQ ID NO: 800, SEQ ID
hsa-miR-24, hsa-miR-146a, hsa-miR-1908,
NO: 671, SEQ ID NO: 814, SEQ ID NO: 560,
hsa-miR-675, hsa-miR-103, hsa-miR-452*
SEQ ID NO: 274
27
A27
SEQ ID NO: 814, SEQ ID NO: 560, SEQ ID
hsa-miR-675, hsa-miR-103, hsa-miR-452*,
NO: 274, SEQ ID NO: 49, SEQ ID NO: 501,
hsa-miR-106a, hsa-miR-621, hsa-miR-1251
SEQ ID NO: 455
28
A28
SEQ ID NO: 49, SEQ ID NO: 501, SEQ ID
hsa-miR-106a, hsa-miR-621, hsa-miR-1251,
NO: 455, SEQ ID NO: 528, SEQ ID NO: 259,
hsa-miR-20a*, hsa-miR-646, hsa-miR-885-3p
SEQ ID NO: 619
29
A29
SEQ ID NO: 528, SEQ ID NO: 259, SEQ ID
hsa-miR-20a*, hsa-miR-646, hsa-miR-885-
NO: 619, SEQ ID NO: 363, SEQ ID NO: 169,
3p, hsa-miR-509-3-5p, hsa-miR-1912, hsa-
SEQ ID NO: 11
miR-20b
30
A30
SEQ ID NO: 363, SEQ ID NO: 169, SEQ ID
hsa-miR-509-3-5p, hsa-miR-1912, hsa-miR-
NO: 11, SEQ ID NO: 9, SEQ ID NO: 768,
20b, hsa-miR-574-5p, hsa-miR-221, hsa-
SEQ ID NO: 552
miR-365
31
A31
SEQ ID NO: 53, SEQ ID NO: 632, SEQ ID
hsa-let-7b, hsa-miR-574-3p, hsa-miR-500,
NO: 526, SEQ ID NO: 790, SEQ ID NO: 806,
hsa-miR-1234, hsa-miR-125a-5p, hsa-miR-
SEQ ID NO: 823, SEQ ID NO: 15, SEQ ID
92b*, hsa-let-7c, hsa-miR-145, hsa-miR-330-
NO: 99, SEQ ID NO: 641, SEQ ID NO: 50
3p, hsa-miR-30e
32
A32
SEQ ID NO: 823, SEQ ID NO: 15, SEQ ID
hsa-miR-92b*, hsa-let-7c, hsa-miR-145, hsa-
NO: 99, SEQ ID NO: 641, SEQ ID NO: 50,
miR-330-3p, hsa-miR-30e, hsa-miR-199a-5p,
SEQ ID NO: 75, SEQ ID NO: 51, SEQ ID
hsa-miR-223, hsa-miR-195, hsa-miR-182,
NO: 13, SEQ ID NO: 129, SEQ ID NO: 750,
hsa-miR-107, hsa-miR-497
SEQ ID NO: 87
33
A33
SEQ ID NO: 51, SEQ ID NO: 13, SEQ ID
hsa-miR-223, hsa-miR-195, hsa-miR-182,
NO: 129, SEQ ID NO: 750, SEQ ID NO: 87,
hsa-miR-107, hsa-miR-497, hsa-miR-593*,
SEQ ID NO: 137, SEQ ID NO: 826, SEQ ID
hsa-miR-422a, hsa-miR-1301, hsa-miR-362-
NO: 778, SEQ ID NO: 232, SEQ ID NO: 644
5p, hsa-miR-214
34
A34
SEQ ID NO: 137, SEQ ID NO: 826, SEQ ID
hsa-miR-593*, hsa-miR-422a, hsa-miR-1301,
NO: 778, SEQ ID NO: 232, SEQ ID NO: 644,
hsa-miR-362-5p, hsa-miR-214, hsa-miR-31*,
SEQ ID NO: 217, SEQ ID NO: 358, SEQ ID
hsa-miR-24, hsa-miR-146a, hsa-miR-1908,
NO: 800, SEQ ID NO: 671, SEQ ID NO: 814
hsa-miR-675
35
A35
SEQ ID NO: 217, SEQ ID NO: 358, SEQ ID
hsa-miR-31*, hsa-miR-24, hsa-miR-146a,
NO: 800, SEQ ID NO: 671, SEQ ID NO: 814,
hsa-miR-1908, hsa-miR-675, hsa-miR-103,
SEQ ID NO: 560, SEQ ID NO: 274, SEQ ID
hsa-miR-452*, hsa-miR-106a, hsa-miR-621,
NO: 49, SEQ ID NO: 501, SEQ ID NO: 455
hsa-miR-1251
36
A36
SEQ ID NO: 560, SEQ ID NO: 274, SEQ ID
hsa-miR-103, hsa-miR-452*, hsa-miR-106a,
NO: 49, SEQ ID NO: 501, SEQ ID NO: 455,
hsa-miR-621, hsa-miR-1251, hsa-miR-20a*,
SEQ ID NO: 528, SEQ ID NO: 259, SEQ ID
hsa-miR-646, hsa-miR-885-3p, hsa-miR-509-
NO: 619, SEQ ID NO: 363, SEQ ID NO: 169
3-5p, hsa-miR-1912
37
A37
SEQ ID NO: 528, SEQ ID NO: 259, SEQ ID
hsa-miR-20a*, hsa-miR-646, hsa-miR-885-
NO: 619, SEQ ID NO: 363, SEQ ID NO: 169,
3p, hsa-miR-509-3-5p, hsa-miR-1912, hsa-
SEQ ID NO: 11, SEQ ID NO: 9, SEQ ID NO:
miR-20b, hsa-miR-574-5p, hsa-miR-221,
768, SEQ ID NO: 552, SEQ ID NO: 789
hsa-miR-365, hsa-miR-22*
38
A38
SEQ ID NO: 11, SEQ ID NO: 9, SEQ ID NO:
hsa-miR-20b, hsa-miR-574-5p, hsa-miR-221,
768, SEQ ID NO: 552, SEQ ID NO: 789,
hsa-miR-365, hsa-miR-22*, hsa-miR-1275,
SEQ ID NO: 495, SEQ ID NO: 854, SEQ ID
hsa-miR-625, hsa-miR-584, hsa-miR-328,
NO: 609, SEQ ID NO: 719, SEQ ID NO: 688
hsa-miR-629
39
A39
SEQ ID NO: 495, SEQ ID NO: 854, SEQ ID
hsa-miR-1275, hsa-miR-625, hsa-miR-584,
NO: 609, SEQ ID NO: 719, SEQ ID NO: 688,
hsa-miR-328, hsa-miR-629, hsa-miR-186,
SEQ ID NO: 313, SEQ ID NO: 667, SEQ ID
hsa-miR-142-3p, hsa-miR-7, hsa-miR-891a,
NO: 491, SEQ ID NO: 320, SEQ ID NO: 84
hsa-miR-1272
40
A40
SEQ ID NO: 53, SEQ ID NO: 526, SEQ ID
hsa-let-7b, hsa-miR-500, hsa-miR-125a-5p,
NO: 806, SEQ ID NO: 15, SEQ ID NO: 641
hsa-let-7c, hsa-miR-330-3p
41
A41
SEQ ID NO: 790, SEQ ID NO: 823, SEQ ID
hsa-miR-1234, hsa-miR-92b*, hsa-miR-145,
NO: 99, SEQ ID NO: 50, SEQ ID NO: 51
hsa-miR-30e, hsa-miR-223
42
A42
SEQ ID NO: 99, SEQ ID NO: 50, SEQ ID
hsa-miR-145, hsa-miR-30e, hsa-miR-223,
NO: 51, SEQ ID NO: 129, SEQ ID NO: 87
hsa-miR-182, hsa-miR-497
43
B1
SEQ ID NO: 53, SEQ ID NO: 632, SEQ ID
hsa-let-7b, hsa-miR-574-3p, hsa-miR-454
NO: 197
44
B2
SEQ ID NO: 197, SEQ ID NO: 526, SEQ ID
hsa-miR-454, hsa-miR-500, hsa-miR-766
NO: 737
45
B3
SEQ ID NO: 737, SEQ ID NO: 14, SEQ ID
hsa-miR-766, hsa-let-7e, hsa-miR-1234
NO: 790
46
B4
SEQ ID NO: 790, SEQ ID NO: 806, SEQ ID
hsa-miR-1234, hsa-miR-125a-5p, hsa-let-7f
NO: 16
47
B5
SEQ ID NO: 16, SEQ ID NO: 823, SEQ ID
hsa-let-7f, hsa-miR-92b*, hsa-let-7c
NO: 15
48
B6
SEQ ID NO: 15, SEQ ID NO: 18, SEQ ID
hsa-let-7c, hsa-let-7g, hsa-miR-145
NO: 99
49
B7
SEQ ID NO: 99, SEQ ID NO: 3, SEQ ID NO:
hsa-miR-145, hsa-let-7i, hsa-miR-130b
622
50
B8
SEQ ID NO: 622, SEQ ID NO: 580, SEQ ID
hsa-miR-130b, hsa-miR-1260, hsa-miR-330-
NO: 641
3p
51
B9
SEQ ID NO: 641, SEQ ID NO: 50, SEQ ID
hsa-miR-330-3p, hsa-miR-30e, hsa-let-7d
NO: 4
52
B10
SEQ ID NO: 4, SEQ ID NO: 436, SEQ ID
hsa-let-7d, hsa-miR-501-3p, hsa-miR-1913
NO: 565
53
B11
SEQ ID NO: 565, SEQ ID NO: 75, SEQ ID
hsa-miR-1913, hsa-miR-199a-5p, hsa-miR-
NO: 5
22
54
B12
SEQ ID NO: 5, SEQ ID NO: 51, SEQ ID NO:
hsa-miR-22, hsa-miR-223, hsa-miR-195
13
55
B13
SEQ ID NO: 13, SEQ ID NO: 129, SEQ ID
hsa-miR-195, hsa-miR-182, hsa-miR-30c
NO: 145
56
B14
SEQ ID NO: 129, SEQ ID NO: 67, SEQ ID
hsa-miR-182, hsa-miR-192, hsa-miR-30c
NO: 145
57
B15
SEQ ID NO: 145, SEQ ID NO: 327, SEQ ID
hsa-miR-30c, hsa-miR-363, hsa-miR-107
NO: 750
58
B16
SEQ ID NO: 53, SEQ ID NO: 632, SEQ ID
hsa-let-7b, hsa-miR-574-3p, hsa-miR-454,
NO: 197, SEQ ID NO: 526, SEQ ID NO: 737
hsa-miR-500, hsa-miR-766
59
B17
SEQ ID NO: 197, SEQ ID NO: 526, SEQ ID
hsa-miR-454, hsa-miR-500, hsa-miR-766,
NO: 737, SEQ ID NO: 14, SEQ ID NO: 790
hsa-let-7e, hsa-miR-1234
60
B18
SEQ ID NO: 737, SEQ ID NO: 14, SEQ ID
hsa-miR-766, hsa-let-7e, hsa-miR-1234, hsa-
NO: 790, SEQ ID NO: 806, SEQ ID NO: 16
miR-125a-5p, hsa-let-7f
61
B19
SEQ ID NO: 14, SEQ ID NO: 790, SEQ ID
hsa-let-7e, hsa-miR-1234, hsa-miR-125a-5p,
NO: 806, SEQ ID NO: 16, SEQ ID NO: 823
hsa-let-7f, hsa-miR-92b*
62
B20
SEQ ID NO: 806, SEQ ID NO: 16, SEQ ID
hsa-miR-125a-5p, hsa-let-7f, hsa-miR-92b*,
NO: 823, SEQ ID NO: 15, SEQ ID NO: 18
hsa-let-7c, hsa-let-7g
63
B21
SEQ ID NO: 823, SEQ ID NO: 15, SEQ ID
hsa-miR-92b*, hsa-let-7c, hsa-let-7g, hsa-
NO: 18, SEQ ID NO: 99, SEQ ID NO: 3
miR-145, hsa-let-7i
64
B22
SEQ ID NO: 15, SEQ ID NO: 18, SEQ ID
hsa-let-7c, hsa-let-7g, hsa-miR-145, hsa-let-
NO: 99, SEQ ID NO: 3, SEQ ID NO: 622,
7i, hsa-miR-130b, hsa-miR-1260
SEQ ID NO: 580
65
B23
SEQ ID NO: 3, SEQ ID NO: 622, SEQ ID
hsa-let-7i, hsa-miR-130b, hsa-miR-1260,
NO: 580, SEQ ID NO: 641, SEQ ID NO: 50,
hsa-miR-330-3p, hsa-miR-30e, hsa-let-7d
SEQ ID NO: 4
66
B24
SEQ ID NO: 641, SEQ ID NO: 50, SEQ ID
hsa-miR-330-3p, hsa-miR-30e, hsa-let-7d,
NO: 4, SEQ ID NO: 436, SEQ ID NO: 565,
hsa-miR-501-3p, hsa-miR-1913, hsa-miR-
SEQ ID NO: 75
199a-5p
67
B25
SEQ ID NO: 436, SEQ ID NO: 565, SEQ ID
hsa-miR-501-3p, hsa-miR-1913, hsa-miR-
NO: 75, SEQ ID NO: 5, SEQ ID NO: 51, SEQ
199a-5p, hsa-miR-22, hsa-miR-223, hsa-
ID NO: 13
miR-195
68
B26
SEQ ID NO: 5, SEQ ID NO: 51, SEQ ID NO:
hsa-miR-22, hsa-miR-223, hsa-miR-195,
13, SEQ ID NO: 343, SEQ ID NO: 129, SEQ
hsa-miR-532-3p, hsa-miR-182, hsa-miR-192
ID NO: 67
69
B27
SEQ ID NO: 343, SEQ ID NO: 129, SEQ ID
hsa-miR-532-3p, hsa-miR-182, hsa-miR-192,
NO: 67, SEQ ID NO: 145, SEQ ID NO: 327,
hsa-miR-30c, hsa-miR-363, hsa-miR-107
SEQ ID NO: 750
70
B28
SEQ ID NO: 145, SEQ ID NO: 327, SEQ ID
hsa-miR-30c, hsa-miR-363, hsa-miR-107,
NO: 750, SEQ ID NO: 675, SEQ ID NO: 87,
hsa-miR-486-3p, hsa-miR-497, hsa-miR-339-
SEQ ID NO: 20
5p
71
B29
SEQ ID NO: 675, SEQ ID NO: 87, SEQ ID
hsa-miR-486-3p, hsa-miR-497, hsa-miR-339-
NO: 20, SEQ ID NO: 137, SEQ ID NO: 237,
5p, hsa-miR-593*, hsa-miR-194, hsa-miR-
SEQ ID NO: 670
627
72
B30
SEQ ID NO: 137, SEQ ID NO: 237, SEQ ID
hsa-miR-593*, hsa-miR-194, hsa-miR-627,
NO: 670, SEQ ID NO: 521, SEQ ID NO: 808,
hsa-miR-93, hsa-miR-197, hsa-miR-101
SEQ ID NO: 198
73
B31
SEQ ID NO: 53, SEQ ID NO: 632, SEQ ID
hsa-let-7b, hsa-miR-574-3p, hsa-miR-454,
NO: 197, SEQ ID NO: 526, SEQ ID NO: 737,
hsa-miR-500, hsa-miR-766, hsa-let-7e, hsa-
SEQ ID NO: 14, SEQ ID NO: 790, SEQ ID
miR-1234, hsa-miR-125a-5p, hsa-let-7f, hsa-
NO: 806, SEQ ID NO: 16, SEQ ID NO: 823
miR-92b*
74
B32
SEQ ID NO: 14, SEQ ID NO: 790, SEQ ID
hsa-let-7e, hsa-miR-1234, hsa-miR-125a-5p,
NO: 806, SEQ ID NO: 16, SEQ ID NO: 823,
hsa-let-7f, hsa-miR-92b*, hsa-let-7c, hsa-let-
SEQ ID NO: 15, SEQ ID NO: 18, SEQ ID
7g, hsa-miR-145, hsa-let-7i, hsa-miR-130b,
NO: 99, SEQ ID NO: 3, SEQ ID NO: 622,
hsa-miR-1260
SEQ ID NO: 580
75
B33
SEQ ID NO: 18, SEQ ID NO: 99, SEQ ID
hsa-let-7g, hsa-miR-145, hsa-let-7i, hsa-miR-
NO: 3, SEQ ID NO: 622, SEQ ID NO: 580,
130b, hsa-miR-1260, hsa-miR-330-3p, hsa-
SEQ ID NO: 641, SEQ ID NO: 50, SEQ ID
miR-30e, hsa-let-7d, hsa-miR-501-3p, hsa-
NO: 4, SEQ ID NO: 436, SEQ ID NO: 565
miR-1913
76
B34
SEQ ID NO: 641, SEQ ID NO: 50, SEQ ID
hsa-miR-330-3p, hsa-miR-30e, hsa-let-7d,
NO: 4, SEQ ID NO: 436, SEQ ID NO: 565,
hsa-miR-501-3p, hsa-miR-1913, hsa-miR-
SEQ ID NO: 75, SEQ ID NO: 5, SEQ ID NO:
199a-5p, hsa-miR-22, hsa-miR-223, hsa-
51, SEQ ID NO: 13, SEQ ID NO: 343
miR-195, hsa-miR-532-3p
77
B35
SEQ ID NO: 75, SEQ ID NO: 5, SEQ ID NO:
hsa-miR-199a-5p, hsa-miR-22, hsa-miR-223,
51, SEQ ID NO: 13, SEQ ID NO: 343, SEQ
hsa-miR-195, hsa-miR-532-3p, hsa-miR-182,
ID NO: 129, SEQ ID NO: 67, SEQ ID NO:
hsa-miR-192, hsa-miR-30c, hsa-miR-363,
145, SEQ ID NO: 327, SEQ ID NO: 750
hsa-miR-107
78
B36
SEQ ID NO: 129, SEQ ID NO: 67, SEQ ID
hsa-miR-182, hsa-miR-192, hsa-miR-30c,
NO: 145, SEQ ID NO: 327, SEQ ID NO: 750,
hsa-miR-363, hsa-miR-107, hsa-miR-486-3p,
SEQ ID NO: 675, SEQ ID NO: 87, SEQ ID
hsa-miR-497, hsa-miR-339-5p, hsa-miR-
NO: 20, SEQ ID NO: 137, SEQ ID NO: 237
593*, hsa-miR-194
79
B37
SEQ ID NO: 675, SEQ ID NO: 87, SEQ ID
hsa-miR-486-3p, hsa-miR-497, hsa-miR-339-
NO: 20, SEQ ID NO: 137, SEQ ID NO: 237,
5p, hsa-miR-593*, hsa-miR-194, hsa-miR-
SEQ ID NO: 670, SEQ ID NO: 521, SEQ ID
627, hsa-miR-93, hsa-miR-197, hsa-miR-
NO: 808, SEQ ID NO: 198, SEQ ID NO: 861
101, hsa-miR-92a
80
B38
SEQ ID NO: 670, SEQ ID NO: 521, SEQ ID
hsa-miR-627, hsa-miR-93, hsa-miR-197,
NO: 808, SEQ ID NO: 198, SEQ ID NO: 861,
hsa-miR-101, hsa-miR-92a, hsa-miR-422a,
SEQ ID NO: 826, SEQ ID NO: 850, SEQ ID
hsa-miR-1470, hsa-miR-1301, hsa-miR-550*,
NO: 778, SEQ ID NO: 43, SEQ ID NO: 232
hsa-miR-362-5p
81
B39
SEQ ID NO: 826, SEQ ID NO: 850, SEQ ID
hsa-miR-422a, hsa-miR-1470, hsa-miR-
NO: 778, SEQ ID NO: 43, SEQ ID NO: 232,
1301, hsa-miR-550*, hsa-miR-362-5p, hsa-
SEQ ID NO: 644, SEQ ID NO: 293, SEQ ID
miR-214, hsa-miR-192*, hsa-miR-31*, hsa-
NO: 217, SEQ ID NO: 720, SEQ ID NO: 358
miR-146b-5p, hsa-miR-24
82
B40
SEQ ID NO: 53, SEQ ID NO: 197, SEQ ID
hsa-let-7b, hsa-miR-454, hsa-miR-766, hsa-
NO: 737, SEQ ID NO: 790, SEQ ID NO: 16
miR-1234, hsa-let-7f
83
B41
SEQ ID NO: 526, SEQ ID NO: 14, SEQ ID
hsa-miR-500, hsa-let-7e, hsa-miR-125a-5p,
NO: 806, SEQ ID NO: 823, SEQ ID NO: 18
hsa-miR-92b*, hsa-let-7g
84
B42
SEQ ID NO: 806, SEQ ID NO: 823, SEQ ID
hsa-miR-125a-5p, hsa-miR-92b*, hsa-let-7g,
NO: 18, SEQ ID NO: 3, SEQ ID NO: 580
hsa-let-7i, hsa-miR-1260

Another embodiment of the present invention is a kit for diagnosing a disease, comprising means for determining an expression profile of a predetermined set of miRNAs in a biological sample, in particular in a blood, plasma, and/or serum sample including whole blood, plasma, serum or fractions thereof, or in a sample comprising peripheral blood mononuclear cells, erythrocytes, leukocytes and/or thrombocytes. Preferably, one or more reference expression profiles or a relevant reference which may be a mathematical function or algorithm—which allows for the diagnosis of the disease—are also provided which show the expression profile of the same set of miRNAs in the same type of biological sample, in particular in a blood and/or serum sample, obtained from one or more healthy subjects. A comparison to said reference expression profile(s) or relevant reference incl. a mathematical function or algorithm allows for the diagnosis of the disease.

The kit is preferably a test kit for detecting a predetermined set of miRNAs in sample by nucleic acid hybridisation and optionally amplification such as PCR or RT-PCR. The kit preferably comprises probes and/or primers and enzymes and reagents, including also reagent for cDNA-synthesis from miRNAs prior to real-time PCR for detecting a predetermined set of miRNAs. Further, the kit may comprise enzymes and reagents, e.g. for cDNA synthesis from miRNAs prior to RT-PCR.

A preferred embodiment of the present invention is a kit for diagnosing multiple sclerosis, comprising means for determining the expression profile of one or more relevant miRNAs presented in the table in FIG. 10A, 10B or 10C as described above, preferably one or more miRNAs selected from the group consisting of hsa-miR-145, hsa-miR-186, hsa-miR-664, hsa-miR-584, hsa-miR-20b, hsa-miR-223, hsa-miR-422a, hsa-miR-142-3p, hsa-let-7c, hsa-miR-151-3p, hsa-miR-491-5p, hsa-miR-942, hsa-miR-361-3p, hsa-miR-22*, hsa-miR-140-5p, hsa-miR-216a, hsa-miR-1275, hsa-miR-367, hsa-miR-146a, hsa-miR-598, hsa-miR-613, hsa-miR-18a*, hsa-miR-302b, hsa-miR-501-5p.

In a preferred embodiment the kit comprises means for determining at least seven, preferably at least 10, 15, 20 or all of the indicated miRNAs. It is particularly preferred to include means for determining the 24, 20, 15, 10 or at least 7 first mentioned miRNAs in the order of their diagnostic significance as represented by their order in the table in FIG. 10A, 10B, or 10C. Further, the kit may comprise means for determining the expression profile of a predetermined set of miRNAs based on Table 1 as described above. The kit for diagnosing MS is particularly suitable for diagnosing MS in a blood, plasma, and/or serum sample or in a sample comprising peripheral blood mononuclear cells, erythrocytes, leukocytes and/or thrombocytes.

The means for determining a predetermined set of miRNAs may for example comprise a microarray comprising miRNA-specific oligonucleotide probes. In a preferred embodiment, the microarray comprises miRNA-specific oligonucleotide probes for one or more miRNAs oligonucleotide probes for one or more miRNAs. Depending on the intended use of the microarray in the diagnostic of a particular disease, probes for different miRNAs may be included.

A microarray intended for use in the diagnosis of multiple sclerosis preferably comprises miRNA specific oligonucleotide probes for one or more miRNAs presented in the table in FIG. 10A, 10B or 10C as described above, preferably for one or more miRNAs selected from the group consisting of hsa-miR-145, hsa-miR-186, hsa-miR-664, hsa-miR-584, hsa-miR-20b, hsa-miR-223, hsa-miR-422a, hsa-miR-142-3p, hsa-let-7c, hsa-miR-151-3p, hsa-miR-491-5p, hsa-miR-942, hsa-miR-361-3p, hsa-miR-22*, hsa-miR-140-5p, hsa-miR-216a, hsa-miR-1275, hsa-miR-367, hsa-miR-146a, hsa-miR-598, hsa-miR-613, hsa-miR-18a*, hsa-miR-302b, hsa-miR-501-5p.

In a preferred embodiment the microarray comprises oligonucleotide probes for determining at least 7, preferably at least 10, 15, 20 or all of the indicated miRNAs. It is particularly preferred to include oligonucleotide probes for determining the most significant miRNAs, which is represented by their order in the table depicted in FIG. 10A, 10B or 10C. In a further embodiment, the microarray comprises oligonucleotide probes for determining miRNA sets based on Table 1 as described above.

The microarray can comprise oligonucleotide probes obtained from known or predicted miRNA sequences. The array may contain different oligonucleotide probes for each miRNA, for example one containing the active mature sequence and another being specific for the precursor of the miRNA. The array may also contain controls such as one or more sequences differing from the human orthologs by only a few bases, which can serve as controls for hybridization stringency conditions. It is also possible to include viral miRNAs or putative miRNAs as predicted from bioinformatic tools. Further, it is possible to include appropriate controls for non-specific hybridization on the microarray.

The invention also relates to sets of oligo- or polynucleotides for diagnosing multiple sclerosis comprising the sequences of at least 7, preferably at least 10, 15, 20 or all of the indicated miRNAs, and/or the complement of such sequences. It is particularly preferred to include oligo- or polynucleotides for detecting the most significant miRNAs, which are represented by their order in the table depicted in FIG. 10A, 10B or 10C. In a further embodiment, the set includes oligo- or polynucleotides for detecting of the miRNA sets based on Table 1 as described above. The oligo- or polynucleotides preferably have a length of 10, 15 or 20 and up to 30, 40, 50, 100 or more nucleotides. The term “oligo- or polynucleotides” includes single- or double-stranded molecules, RNA molecules, DNA molecules or nucleic acid analogs such as PNA or LNA.

Another embodiment of the present invention relates to a method for the assessment of a clinical condition related to multiple sclerosis of a patient.

Recent developments have shown that there is a tendency towards smaller sets of biomarkers for the detection of diseases. However, for single biomarkers and small biomarker sets, there is only a basic understanding whether these biomarkers are specific for only the single diseases or whether they occur in any other disease.

Therefore, the present inventors developed a novel class of diagnostic tests improving the current test scenarios. The inventors found out that a variety of diseases are correlated with a specific expression profile of miRNAs. In case a patient is affected by a particular disease, several miRNAs are present in larger amounts compared to a healthy normal control, whereas the amount of other miRNAs is decreased. Interestingly, the amount of some miRNAs is deregulated, i.e. increased or decreased, in more than one disease. The miRNA profile for a particular disease therefore shows conformity with the miRNA profile of other diseases in regard of individual miRNAs while other miRNAs show significant differences. If the expression profile of a large variety of miRNAs in a biological sample of a patient is measured, the comparison of the expression profile with a variety of reference expression profiles which are each characteristic for different diseases makes it possible to obtain information about the clinical condition of a certain patient and to determine, which disease(s) is/are present in said patient.

A further subject matter of the invention is a method for the assessment of a clinical condition related to multiple sclerosis of a patient comprising the steps

    • (a) providing a sample from the patient,
    • (b) determining a predetermined set of miRNAs in said sample to obtain a miRNA expression profile,
    • (c) comparing said miRNA expression profile with a plurality of miRNA reference expression profiles characteristic for different diseases, and
    • (d) assessing the clinical condition of the patient based on the comparison of step (c).

The inventors found out that the above method for the assessment of a clinical condition makes it possible to carry out an integrative diagnosis of a wide variety of diseases, particularly including multiple sclerosis. Comparing a miRNA profile obtained from a biological sample of a patient whose clinical condition is not known with a plurality of reference profiles characteristic for different diseases enables the diagnosis of a wide variety of diseases with high specificity and sensitivity.

A “biological sample” in terms of the invention means a sample of biological tissue or fluid as described hereinabove. Examples of biological samples are sections of tissues, blood, blood fractions, plasma, serum, urine or samples from other peripheral sources.

The set of miRNAs determined in step (d) preferably includes a large number of different miRNAs. It is particularly preferred to use at least 10, 20, 30, 50, preferably at least 100, 200, 500 or 1,000 miRNAs. Most preferably, all known miRNAs are included in the set of miRNAs determined in step (b) Such a complex set of miRNA-biomarkers enables a diagnosis with higher specificity and sensitivity compared to single biomarkers or sets of only a few dozens of such markers.

The determination of the set of miRNAs can be done as described herein above. Preferably, the determination is done on an experimental platform which shows a high degree of automation to minimize experimental variations, measure results time- and cost-efficiently, measures results highly reproduceably and be able for measuring more than one sample at once in order to ensure a high throughput.

Step (c) preferably includes a comparison of the miRNA profile measured for a patient with a large number of different reference profiles to provide information about the presence of as many different diseases as possible. The reference expression profiles may be laid down in a database, e.g. an internet database, a centralized or a decentralized database. The reference profiles do not necessarily have to include information about all miRNAs included in step (b), which are determined in the sample of the patient. It is, according to the invention, sufficient if the reference profile provides information on those miRNAs which are altered to a large extent compared to the condition of a healthy individual in case of the presence of a disease. Alternatively, the said relevant reference may be a mathematical function or algorithm.

Preferably, an miRNA reference profile or the relevant reference according to the invention provides information on miRNA expression characteristic for a particular disease in the same type of biological sample as used in step (b) for determining a predetermined set of miRNAs in a sample from a patient. This means that, if a patient with an unknown disease is to be classified with the analysis of a blood sample, the comparison is preferably made with miRNA reference expression profiles, which do also relate to the miRNA expression pattern in a blood sample.

The reference profiles or the relevant reference characteristic for particular diseases provide information on one or more miRNAs, which are, in case of the disease, highly deregulated, for example strongly increased or decreased, as compared to a healthy condition. It is not necessary for the reference profiles to provide information about all miRNAs included in the set of biomarkers determined in step (b). However, the more miRNAs are included in the reference profile or relevant reference, the more precise the diagnosis will be. If, for example, a reference profile for lung cancer is included, it is preferred to include the characteristic miRNAs for lung cancer. Equivalently, it is preferred to include into a reference profile for multiple sclerosis the characteristic miRNAs for multiple sclerosis as described hereinabove as well.

Another embodiment of this aspect of the invention is a kit for the assessment of a clinical condition related to multiple sclerosis of a patient comprising

(a) means for determining a predetermined set of miRNAs in a biological sample from a patient, and

(b) a plurality of miRNA reference expression profiles characteristic for different diseases or a mathematical function that allows for the diagnosis on the basis of the data derived from the miRNA expression profiles of a patient.

The set of miRNAs to be determined in a biological sample from a patient preferably includes a large number of different miRNAs. It is particularly preferred to include all known miRNAs in the set of miRNAs to be determined. In each case, said predetermined set of miRNAs should include those miRNAs for which information is provided in the reference profiles characteristic for particular diseases. It is understood that only in case the set of miRNAs determined in a biological sample from a patient comprises those miRNAs included in the reference profile/reference for a disease, a diagnosis regarding this particular disease can be provided or otherwise the diagnosis may be less informative.

The assessment of a clinical condition of a patient according to the invention is suitable for diagnosing any diseases which are correlated with a characteristic miRNA profile. Accordingly, the kit for the assessment of a clinical condition preferably includes reference profiles/references for a plurality of diseases that are correlated with a characteristic miRNA profile. It is understood that all miRNAs that are significantly deregulated in the disease states for which reference profiles are provided should be included in the set of miRNAs to be determined in a biological sample from a patient. If the kit for the assessment of a clinical condition of a patient should provide information regarding, e.g. lung cancer or multiple sclerosis, a reference profile should be available providing information about the significantly deregulated miRNAs compared to a normal or any other relevant control individual or any other relevant control individual(s). A kit for the assessment of a clinical condition shall provide information on the presence of multiple sclerosis, a reference profile characteristic for multiple sclerosis should be included. Said reference profile preferably includes information on those miRNAs that are most significantly deregulated in the case of MS. The relevant miRNAs are as disclosed hereinabove.

The invention will now be illustrated by the following figures and the non-limiting experimental examples.

FIGURES

FIG. 1:

Scheme of a miRNA hybridization assay for use in the invention.

    • miRNA capture probes consist of 1 miRNA probe sequence stretch that is linked to support via 3′-end or alternatively by 5′-end (not depicted here)
    • the miRNA probe sequence stretches are complementary to miRNA target sequences
    • each miRNA capture probe can bind 1 miRNA target sequences
    • the miRNA target sequences are labeled prior to hybridisation (e.g. by biotin labeling)

FIG. 2:

Scheme of an miRNA tandem hybridization assay for use in the invention

    • miRNA capture probes consist of 2 DNA-based miRNA probe sequence stretches that are linked to each other by a spacer element
    • the miRNA probe sequence stretches are complementary to miRNA target sequences
    • each miRNA capture probe can bind 2 miRNA target sequences
    • the spacer sequence consists of 0-8 nucleotides

      the miRNA target sequences are labeled prior to hybridisation (e.g. by biotin labeling)

FIG. 3:

miRNA RAKE-Assay for use in the invention (PT Nelson et al., Nature Methods, 2004, 1(2), 1)

    • the miRNA capture probes consist of one miRNA probe sequence stretch (green) and one elongation element (orange)
    • probes are oriented 5′→3′, presenting a free terminal 3′-OH
    • the miRNA probe sequence stretch (green) is complementary to miRNA target sequences (dark green)
    • the elongation sequences (orange) can be freely chosen and is typically between 1-12 nucleotides long, preferably a homomeric sequence
    • each miRNA capture probe can bind 1 miRNA target sequence
    • the miRNA target sequences are NOT labeled prior to hybridisation
    • Labeling occurs after hybridisation during elongation by polymerase extension reaction

Biochip is not reusable due to exonuclease treatment

FIG. 4:

    • miRNA MPEA-Assay for use in the invention (Vorwerk S. et al., Microfluidic-based enzymatic on-chip labeling of miRNAs, N. Biotechnol. 2008; 25(2-3):142-9. Epub 2008 Aug. 20)
    • the miRNA capture probes consist of one miRNA probe sequence stretch (green) and one elongation element (orange)
    • probes are oriented 3′→5′, presenting a free terminal 5′-OH

      the miRNA probe sequence stretch (green) is complementary to miRNA target sequences (dark green)

    • the elongation sequences (orange) can be freely chosen and is typically between 1-12 nucleotides long, preferably a homomeric sequence
    • each miRNA capture probe can bind 1 miRNA target sequences
    • the miRNA target sequences are NOT labeled prior to hybridisation
    • Labeling occurs after hybridisation during elongation by polymerase extension reaction
    • Biochip is reusable after removal of target/elongated target

FIG. 5:

miRNA capture probe design (design MPEA/RAKE)

Depicted is the design of a capture probe for the exemplary miRNA human mature miRNA let-7a for use in the various types of hybridization assays shown in FIGS. 1-4. SP=spacer element; EL=elongation element

FIG. 6:

Spacer Element.

Capture probes for use in e.g. a tandem hybridization assay as shown in FIG. 2 may comprise a spacer element SP. The spacer element represents a nucleotide sequence with n=0-12 nucleotides chosen on the basis of showing low complementarity to potential target sequences, therefore resulting in no to low degree of crosshybridization to target mixture. Preferably, n=0, i.e. there is no spacer between the 2 miRNA probe sequence stretches.

FIG. 7:

Elongation element (Design Probe MPEA/RAKE)

A capture probe, e.g. for use in a RAKE or MPEA assay as shown in FIGS. 3 and 4 may include an elongation element. The elongation element comprises a nucleotide sequence with N=0-30 nucleotides chosen on the basis of showing low complementarity to potential target sequences, therefore resulting in no to low degree of crosshybridization to target mixture. Preferred is a homomeric sequence stretch -Nn- with n=1-30, N=A or C, or T, or G. Especially preferred is a homomeric sequence stretch -Nn- with n=1-12, N=A or C, or T, or G.

FIG. 8:

Pearson Correlation Coefficient depending on the number of elongated nucleotides in capture probes in an MPEA assay.

FIG. 9:

Diagram describing the general approach for determining miRNA signatures for use as biomarkers in disease diagnosis.

FIG. 10A:

Overview of all miRNAs that are found to be differentially regulated in blood samples of MS patients, grouped according to their diagnostic information represented by the respective area under the curve (AUC) value in receiver-operator characteristic curves. The first 193 entries represent miRNAs with t-test p-values <0.05.

FIG. 10B:

Overview of all miRNAs that are found to be differentially regulated in blood samples of MS patients, grouped according to their diagnostic information represented by the t-test significance. The first 165 entries represent miRNAs with t-test p-values<0.05. The grouping is based on additional information derived from further patients (compared to FIG. 10A).

FIG. 10C:

A further list of 308 entries representing miRNAs with t-test p-values<0.05. The grouping is based on additional information derived from further patients (compared to FIGS. 10A and 10B).

FIG. 11:

Histogram plots of the logarithm of fold quotients, the raw t-test p-values and the adjusted p-values. The histogram plots show in the upper part a histogram of logarithmized fold changes, detailing a manifold up-regulated miRNAs in Multiple Sclerosis compared to healthy subjects. The middle and lower part of the Figure describe raw significance values and adjusted significance values providing evidence for a wide variety of deregulated miRNAs that are well suited for MS detection.

FIGS. 12A and 12B:

This Figure presents for two miRNAs, namely miR-145 and miR-186, the intensity values for all MS (left part) and control (right part) samples.

Both miRNAs show a significant up-regulation in MS.

FIG. 13:

The Box-plots denote the accuracy, specificity and sensitivity of the diagnostic test of the invention. In comparison, random classification results are shown, providing evidence for a decreased classification accuracy of about 50% (corresponding to random guessing). Furthermore, the graphic shows that the true classification scenario is more stable while the random classifications entail high variances.

FIG. 14:

This graph illustrates a disease network containing nodes for each disease as blue-colored rhombs (lung cancer, multiple sclerosis, pancreatic cancer, melanoma and Wilm tumor). Additionally, it contains differentially colored and sized nodes, representing biomarker sets. The size of these nodes represents the number of biomarkers inside the set (additionally the number of biomarkers is given inside the corresponding circles). The color represents the information on the number of diseases that are significant for the biomarkers in the set. The nodes are connected to the respective diseases, e.g., each green colored node contains biomarkers, significant for two diseases and thus each green node is connected to two disease nodes. (blue=significant to one disease, rose=significant for 3 diseases, purple=significant to 5 diseases).

FIGS. 15a)-c):

The bar graphs in FIGS. 15a), b) and c) depict the disease probability for a “normal” individual a), for an individual suffering from lung cancer b) and for an individual suffering from multiple sclerosis c).

EXAMPLES

Example 1

Multiple Sclerosis

1.1 Materials and Methods

1.1.1 Samples

Blood samples were obtained with patients' informed consent.

1.1.2 miRNA Microarray Screening

Blood of MS patients and volunteers without known disease was extracted in PAXgene Blood RNA tubes (BD, Franklin Lakes, N.J. USA). For each blood donor, 5 ml of peripheral blood were obtained. Total RNA was extracted from blood cells using the miRNeasy Mini Kit (Qiagen GmbH, Hilden, Germany) and the RNA has been stored at −70° C. Samples were analyzed with the Geniom Realtime Analyzer (GRTA, febit GmbH, Heidelberg, Germany) using the Geniom Biochip miRNA homo sapiens. Each array contains 7 replicates of 866 miRNAs and miRNA star sequences as annotated in the Sanger mirBase 12.0. Sample labelling with Biotine has been carried out by multifluidic-based enzymatic on-chip labelling of miRNAs (MPEA).

Following hybridization for 16 hours at 42° C. the biochip was washed automatically and a program for signal enhancement was processed with the GRTA. The resulting detection pictures were evaluated using the Geniom Wizard Software. For each array, the median signal intensity was extracted from the raw data file such that for each miRNA seven intensity values have been calculated corresponding to each replicate copy of mirBase on the array. Following background correction, the seven replicate intensity values of each miRNA were summarized by their median value. To normalize the data across different arrays, quantile normalization was applied and all further analyses were carried out using the normalized and background subtracted intensity values.

1.1.3 Statistical Analysis

After having verified the normal distribution of the measured data, a parametric t-test (unpaired, two-tailed) was carried out for each miRNA separately, to detect miRNAs that show a different behavior in different groups of blood donors. The resulting p-values were adjusted for multiple testing by Benjamini-Hochberg adjustment.

To find relations of the detected miRNAs to other diseases the Human miRNA Disease Database was used. In more detail, a bipartite network was built where nodes correspond either to a miRNA or to a diseases. Only edges between miRNA and diseases nodes are allowed, where an edge between miRNA A and disease B means that the miRNA A is differentially regulated in disease B. Since for MS no deregulated miRNAs are known the node “MultipleSclerosis” was added to this network and linked to all miRNAs that were significant in the analysis.

In addition to the single biomarker analysis and network analysis, classification of samples using miRNA patterns was carried out using Support Vector Machines (SVM) as implemented in the R e1071 package. In detail, different kernel (linear, polynomial, sigmoid, radial basis function) Support Vector Machines were evaluated, where the cost parameter was sampled from 0.01 to 10 in decimal powers. The measured miRNA profiles were classified using 100 repetitions of standard 10-fold cross-validation. As a subset selection technique we applied a filter approach based on t-test. In detail, the s miRNAs with lowest p-values were computed on the training set in each fold of the cross validation, where s was sampled from 1 to 866. The respective subset was used to train the SVM and to carry out the prediction of the test samples. As result, the mean accuracy, specificity, and sensitivity were calculated together with the 95% Confidence Intervals (95% CI) for each subset size. To check for overtraining permutation tests were applied. Here the class labels were sampled randomly and classifications were carried out using the permuted class labels. All statistical analyzes were performed using R.

1.2 Results

1.2.1 miRNA Experiments

The expression of 866 miRNAs and miRNA star sequences was analyzed in blood cells of 22 patients with MS. As a control blood cells of 22 volunteers without known disease were used.

Following RNA isolation and the novel on-chip labeling technique, the miRNA expression profiles were measured by the Geniom Bioship miRNA homo sapiens in the GRTA (febit GmbH, Heidelberg). Following intensity value computation and quantile normalization of the miRNA profiles, a mean correlation value of 0.97 for technical replicates was determined by using purchased total RNA from Ambion (four heart and four liver replicates). For the biological replicates the different tumor samples were compared between each other and the different normal samples were compared between each other. The biological replicates showed a mean correlation of 0.87 and a variance of 0.009.

1.2.2 Ruling Out the Influence of Age and Gender

To cross-check that age and gender do not have an influence on our analysis, t-tests for the normal samples were computed. In the case of males versus females there were no statistically significant deregulated miRNA. The most significant miRNA, hsa-miR-423, showed an adjusted significance level of 0.78.

To test for the influence of donor age the profiles obtained from samples obtained from the oldest versus youngest patients were compared by splitting the group in half based on age. Here, the most significant miRNA, miR-890, obtained an adjusted p-value of 0.87. As for gender, there were no deregulated miRNAs, thus providing evidence that age and gender do not have a substantial influence on the miRNA profiles.

Additionally, we checked the influence of a therapy. Patients were either treated with glatiramer acetate (n=9), or interferon-β (n=10), or did not get a therapy (n=1). We compared the group of patients treated with glatiramer acetate to the group treated with interferon-β. As for the gender and the age we did not find any significant miRNA.

1.2.3 Single Deregulated miRNAs

Hypothesis testing was applied to identify miRNAs deregulated in the blood cells of MS patients as compared to the blood cells of the controls. Following verification of an approximately normal distribution, two-tailed unpaired t-tests were performed for each miRNA. The respective p-values were adjusted for multiple testing by the Benjamini-Hochberg approach. In total 193 miRNAs significantly deregulated in blood cells of MS patients as compared to the controls were detected. Histogram plots of the logarithm of fold quotients, the raw t-test p-values and the adjusted p-values are presented in FIG. 11. A complete list of deregulated miRNAs is given in the Table in FIG. 10A. The miRNAs that were most significantly deregulated included hsa-miR-145 (5.25*10−9), hsa-miR-186 (3.42*10−7), hsa-miR-664 (1.20′10−5), hsa-miR-20b (1.98*10−5), hsa-miR-584 (1.98*10−5), hsa-miR-223 (2.14′10−5), hsa-miR-422a (2.87*10−5), hsa-miR-142-3p (3.01*10−5) and hsa-let-7c (7.68*10−5). For the two best miRNAs, hsa-miR-186 and hsa-miR-145, bar-plots showing the intensity values for all MS and control samples are presented in FIGS. 12a and 12b.

Notably, all the above-mentioned miRNAs showed a significant up-regulation in MS besides miR-20b. Table 2 shows the 24 most deregulated miRNAs. Of these 91.7% were up-regulated in MS while 8.3% were down-regulated, providing evidence for an overall up-regulation of miRNAs in MS.

Additionally for the best miRNAs receiver operator characteristic curves (ROC) and the area under the curve value (AUC) were computed. The higher the AUC, the better the miRNA biomarker is, where a maximal value of 1 for miRNA A would mean that the highest control reactivity would be lower than the lowest MS intensity of miRNA A. For the best miRNA hsa-miR-145 an AUC value of 0.96 was obtained and four of the 44 samples were wrong classified (2 Ms sera as controls, so-called False Negatives, and 2 controls classified as MS samples, so-called False Positives).


TABLE 2
24 most significant miRNAs for MS
median
median
Log
miRNA
g1
g2
qmedian
(qmedian)
raw Pval
adj. Pval
AUC
hsa-miR-145
602.719
174.344
3.457
1.240
6.08E−12
5.25E−09
0.962
hsa-miR-186
265.295
77.719
3.414
1.228
7.91E−10
3.42E−07
0.961
hsa-miR-664
707.168
285.703
2.475
0.906
4.17E−08
1.20E−05
0.916
hsa-miR-584
332.922
106.969
3.112
1.135
1.15E−07
1.98E−05
0.897
hsa-miR-20b
2689.207
5810.586
0.463
−0.770
9.83E−08
1.98E−05
0.056
hsa-miR-223
5118.574
2579.250
1.985
0.685
1.49E−07
2.14E−05
0.964
hsa-miR-422a
373.953
189.219
1.976
0.681
2.32E−07
2.87E−05
0.870
hsa-miR-142-3p
215.375
40.516
5.316
1.671
2.79E−07
3.01E−05
0.934
hsa-let-7c
1948.098
950.223
2.050
0.718
8.00E−07
7.68E−05
0.889
hsa-miR-151-3p
1021.363
571.344
1.788
0.581
1.81E−06
0.000156587
0.883
hsa-miR-491-5p
241.000
153.563
1.569
0.451
2.05E−06
0.000160884
0.876
hsa-miR-942
112.969
38.094
2.966
1.087
5.09E−06
0.000366452
0.882
hsa-miR-361-3p
325.766
181.375
1.796
0.586
5.77E−06
0.000383235
0.852
hsa-miR-22*
178.938
103.844
1.723
0.544
6.24E−06
0.000385004
0.868
hsa-miR-140-5p
105.063
48.250
2.177
0.778
7.99E−06
0.000399262
0.874
hsa-miR-216a
202.219
315.828
0.640
−0.446
8.24E−06
0.000399262
0.060
hsa-miR-1275
210.203
116.969
1.797
0.586
7.04E−06
0.000399262
0.907
hsa-miR-367
92.500
160.375
0.577
−0.550
8.32E−06
0.000399262
0.138
hsa-miR-146a
470.359
271.342
1.733
0.550
9.61E−06
0.000437137
0.862
hsa-miR-598
140.531
91.000
1.544
0.435
1.29E−05
0.000556416
0.841
hsa-miR-613
60.781
19.000
3.199
1.163
1.67E−05
0.000687276
0.862
hsa-miR-18a*
490.891
233.672
2.101
0.742
2.02E−05
0.000794863
0.876
hsa-miR-302b
54.469
21.406
2.545
0.934
2.23E−05
0.000838901
0.855
hsa-miR-501-5p
139.938
79.563
1.759
0.565
2.60E−05
0.000936279
0.866

1.2.4 Relation to Other Diseases

Since there is no evidence for de-regulated miRNAs in MS patients in the literature, it was checked whether the detected 193 miRNAs are already related to other human diseases. To this end, the Human microRNA Disease Database (HMDD) was grasped. This comprehensive database contains for over 100 human diseases information on deregulated miRNAs. Altogether, over 2000 relations are included in the HMDD. To analyze the respective data, a bipartite graph was created were nodes are either miRNAs or human diseases, and edges between a miRNA and a disease mean that the respective miRNA is deregulated in the respective disease.

Thereby, a network containing 452 nodes was created, 137 belonging to diseases and 315 to miRNAs. The network also contained 1617 unique edges (some relations between miRNAs and diseases have been published in multiple papers). As mentioned previously, MS is not included as disease in this network. Thus, the network was modified as followings: a disease node “MultipleSclerosis” was added and edges between this node and all significant miRNAs were created. Additionally, all disease nodes that are not linked to any MS miRNA and all miRNAs belonging only to removed disease nodes were removed. The novel network thus contains only those miRNAs that are significant in MS and other diseases and those that are significant in MS, only. This shrunken network contained 77 disease nodes together with the 193 significant miRNAs. Remarkably, only 43 of the 193 (22%) miRNAs were related to a disease other than MS while the remaining 78% miRNAs were only connected to MS. Of these 146 miRNAs, 36 were so-called star sequences.

Altogether, these results provide strong evidence that the detected complex miRNA profile is not disease specific but rather specific for MS.

1.2.5 Evaluating Complex Fingerprints

As discussed in Section 1.2.3, the best miRNA suffices to classify 20 of 22 MS samples and 20 of 22 control samples correctly. This obviously corresponds to a high specificity, sensitivity and accuracy of 90.8%. However, these results are not validated by a re-sampling technique as bootstrapping or cross-validation and are based only on a single marker.

In order to improve the already high classification accuracy and the statistical reliability the predictive power of multiple miRNAs was combined by using statistical learning techniques. In detail, Support Vector Machines with different kernels (linear, polynomial, sigmoid, radial basis function) were applied to the data and a hypothesis test based subset selection was carried out as described in Material and Methods. To gain statistical significance 100 repetitions of 10-fold cross validation were carried out. Likewise, 100 repetitions for the permutation tests were computed where samples with randomly assigned class labels were investigated.

The best results were obtained with radial basis function Support Vector Machines and a subset of 24 miRNAs (see Table 2). These miRNAs allowed for the discrimination between blood samples of MS patients and blood samples of controls with an accuracy of 95.5% a specificity of 95.5%, and a sensitivity of 95.5%.

The permutation tests showed significantly decreased accuracy, specificity, and sensitivity rates, as detailed in FIG. 13. These results show that the obtained results are not due to an overfit of the statistical model on the miRNA fingerprints.

Additionally, it was checked whether the relevant miRNAs were linked to one of over 100 other diseases as annotated in the HMDD. Remarkable over 80% of the respective miRNAs have not been linked to other diseases, so far.

Example 2

Molecular Clinical Thermometer

For the molecular clinical thermometer, an arbitrary machine learning (feature extraction/classification/regression/clustering) technique can be applied. The workflow does not depend on the applied method that can be seen as a black box.

First, a sophisticated large set of samples for the diseases to be investigated has to be measured using a larger amount of biomarkers. This set, consisting of a p×n matrix where n is the number of samples and p the number of biomarkers, is commonly denoted as training data set.

Now, a combination of feature extraction and supervised learning techniques (the process can be also carried out with slight modifications using unsupervised techniques) is applied to generate a statistical model, which describes the training data well. Here, it is essential to control the model complexity in order to avoid so-called overtraining of the statistical models. Although, in general, multi-class cases can be carried out, we focus on two class comparisons, i.e., normal versus cancer 1, normal versus cancer 2, cancer 1 versus cancer 2.

Given the trained models and a new biomarker profile, the statistical model can be used to compute the probability for each class and this new sample. Only one example are support vector machines, where the distance of a sample to the separating hyperplane can be used to estimate the class probability via a regression approach. The specificity and sensitivity can be trade-off by shifting the probability threshold (which usually should be 0.5 or 50%).

The probabilities in the previously described step can be used to generate so-called disease probability plots (DPP). These plots contain for each class and a single sample the probabilities to belong to a certain class. In detail, each class is described by a colored line of length 100 (representing a percentage range), where the lower rate is colored green (representing small probabilities) and the higher range red (higher probabilities). For each class, an arrow marks the probability for the patient and the respective disease. For class “normal” the minimal and maximal probability to be normal are shown.

The DPPs thus allow for visualizing the complex statistical evaluation in a simple and well interpretable way.

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<160> NUMBER OF SEQ ID NOS: 868

<210> SEQ ID NO: 1

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 1

ucguaccgug aguaauaaug cg 22

<210> SEQ ID NO: 2

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 2

ugaggggcag agagcgagac uuu 23

<210> SEQ ID NO: 3

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 3

ugagguagua guuugugcug uu 22

<210> SEQ ID NO: 4

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 4

agagguagua gguugcauag uu 22

<210> SEQ ID NO: 5

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 5

aagcugccag uugaagaacu gu 22

<210> SEQ ID NO: 6

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 6

uagcagcaca uaaugguuug ug 22

<210> SEQ ID NO: 7

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 7

ugagguagua aguuguauug uu 22

<210> SEQ ID NO: 8

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 8

ugugcaaauc uaugcaaaac uga 23

<210> SEQ ID NO: 9

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 9

ugagugugug ugugugagug ugu 23

<210> SEQ ID NO: 10

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 10

acugccccag gugcugcugg 20

<210> SEQ ID NO: 11

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 11

caaagugcuc auagugcagg uag 23

<210> SEQ ID NO: 12

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 12

cauugcacuu gucucggucu ga 22

<210> SEQ ID NO: 13

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 13

uagcagcaca gaaauauugg c 21

<210> SEQ ID NO: 14

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 14

ugagguagga gguuguauag uu 22

<210> SEQ ID NO: 15

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 15

ugagguagua gguuguaugg uu 22

<210> SEQ ID NO: 16

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 16

ugagguagua gauuguauag uu 22

<210> SEQ ID NO: 17

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 17

ugagguagua gguuguauag uu 22

<210> SEQ ID NO: 18

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 18

ugagguagua guuuguacag uu 22

<210> SEQ ID NO: 19

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 19

uaccacaggg uagaaccacg g 21

<210> SEQ ID NO: 20

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 20

ucccuguccu ccaggagcuc acg 23

<210> SEQ ID NO: 21

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 21

uuaucagaau cuccaggggu ac 22

<210> SEQ ID NO: 22

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 22

ucuacaaagg aaagcgcuuu cu 22

<210> SEQ ID NO: 23

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 23

acugcccuaa gugcuccuuc ugg 23

<210> SEQ ID NO: 24

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 24

uucaaguaau ucaggauagg u 21

<210> SEQ ID NO: 25

<211> LENGTH: 19

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 25

aggcugcgga auucaggac 19

<210> SEQ ID NO: 26

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 26

agcucggucu gaggccccuc agu 23

<210> SEQ ID NO: 27

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 27

acugcugagc uagcacuucc cg 22

<210> SEQ ID NO: 28

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 28

uagcaccauc ugaaaucggu ua 22

<210> SEQ ID NO: 29

<211> LENGTH: 27

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 29

accuucuugu auaagcacug ugcuaaa 27

<210> SEQ ID NO: 30

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 30

cugugcgugu gacagcggcu ga 22

<210> SEQ ID NO: 31

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 31

ugugcaaauc caugcaaaac uga 23

<210> SEQ ID NO: 32

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 32

agguuguccg uggugaguuc gca 23

<210> SEQ ID NO: 33

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 33

cauuauuacu uuugguacgc g 21

<210> SEQ ID NO: 34

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 34

cucccacaug caggguuugc a 21

<210> SEQ ID NO: 35

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 35

uaguaccagu accuuguguu ca 22

<210> SEQ ID NO: 36

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 36

gggagccagg aaguauugau gu 22

<210> SEQ ID NO: 37

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 37

aaugacacga ucacucccgu uga 23

<210> SEQ ID NO: 38

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 38

ugagcgccuc gacgacagag ccg 23

<210> SEQ ID NO: 39

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 39

ugucacucgg cucggcccac uac 23

<210> SEQ ID NO: 40

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 40

cggguggauc acgaugcaau uu 22

<210> SEQ ID NO: 41

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 41

cgaaucauua uuugcugcuc ua 22

<210> SEQ ID NO: 42

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 42

ugaccgauuu cuccuggugu uc 22

<210> SEQ ID NO: 43

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 43

ugucuuacuc ccucaggcac au 22

<210> SEQ ID NO: 44

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 44

aaucacuaac cacacggcca gg 22

<210> SEQ ID NO: 45

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 45

uaaagugcuu auagugcagg uag 23

<210> SEQ ID NO: 46

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 46

uuauaauaca accugauaag ug 22

<210> SEQ ID NO: 47

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 47

ggauuccugg aaauacuguu cu 22

<210> SEQ ID NO: 48

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 48

uaagugcuuc cauguuuuag uag 23

<210> SEQ ID NO: 49

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 49

aaaagugcuu acagugcagg uag 23

<210> SEQ ID NO: 50

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 50

uguaaacauc cuugacugga ag 22

<210> SEQ ID NO: 51

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 51

ugucaguuug ucaaauaccc ca 22

<210> SEQ ID NO: 52

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 52

cuggacugag ccgugcuacu gg 22

<210> SEQ ID NO: 53

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 53

ugagguagua gguugugugg uu 22

<210> SEQ ID NO: 54

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 54

ugugacagau ugauaacuga aa 22

<210> SEQ ID NO: 55

<211> LENGTH: 18

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 55

ugcuuccuuu cagagggu 18

<210> SEQ ID NO: 56

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 56

aaaccguuac cauuacugag uu 22

<210> SEQ ID NO: 57

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 57

aaagugcauc uuuuuagagg au 22

<210> SEQ ID NO: 58

<211> LENGTH: 26

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 58

aaguaguugg uuuguaugag augguu 26

<210> SEQ ID NO: 59

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 59

gacacgggcg acagcugcgg ccc 23

<210> SEQ ID NO: 60

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 60

ucccccaggu gugauucuga uuu 23

<210> SEQ ID NO: 61

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 61

aguuuugcau aguugcacua ca 22

<210> SEQ ID NO: 62

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 62

aucaugaugg gcuccucggu gu 22

<210> SEQ ID NO: 63

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 63

cuccugagcc auucugagcc uc 22

<210> SEQ ID NO: 64

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 64

aaaaugguuc ccuuuagagu gu 22

<210> SEQ ID NO: 65

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 65

aagugcuucc uuuuagaggg uu 22

<210> SEQ ID NO: 66

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 66

cucuagaggg aagcgcuuuc ug 22

<210> SEQ ID NO: 67

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 67

cugaccuaug aauugacagc c 21

<210> SEQ ID NO: 68

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 68

aagugaucua aaggccuaca u 21

<210> SEQ ID NO: 69

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 69

ucgaggagcu cacagucuag u 21

<210> SEQ ID NO: 70

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 70

uggacugccc ugaucuggag a 21

<210> SEQ ID NO: 71

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 71

uagcagcggg aacaguucug cag 23

<210> SEQ ID NO: 72

<211> LENGTH: 19

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 72

agguugacau acguuuccc 19

<210> SEQ ID NO: 73

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 73

gguggcccgg ccgugccuga gg 22

<210> SEQ ID NO: 74

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 74

cuauacgacc ugcugccuuu cu 22

<210> SEQ ID NO: 75

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 75

cccaguguuc agacuaccug uuc 23

<210> SEQ ID NO: 76

<211> LENGTH: 17

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 76

ucucgcuggg gccucca 17

<210> SEQ ID NO: 77

<211> LENGTH: 19

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 77

aauggauuuu uggagcagg 19

<210> SEQ ID NO: 78

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 78

aacaauaucc uggugcugag ug 22

<210> SEQ ID NO: 79

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 79

auguaugugu gcaugugcau g 21

<210> SEQ ID NO: 80

<211> LENGTH: 19

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 80

auggauaagg cuuuggcuu 19

<210> SEQ ID NO: 81

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 81

gcagcagaga auaggacuac guc 23

<210> SEQ ID NO: 82

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 82

uggagagaaa ggcaguuccu ga 22

<210> SEQ ID NO: 83

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 83

gcgaggaccc cucggggucu gac 23

<210> SEQ ID NO: 84

<211> LENGTH: 26

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 84

gaugaugaug gcagcaaauu cugaaa 26

<210> SEQ ID NO: 85

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 85

uucuggaauu cugugugagg ga 22

<210> SEQ ID NO: 86

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 86

uuuuucauua uugcuccuga cc 22

<210> SEQ ID NO: 87

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 87

cagcagcaca cugugguuug u 21

<210> SEQ ID NO: 88

<211> LENGTH: 18

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 88

ucagcuggcc cucauuuc 18

<210> SEQ ID NO: 89

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 89

uagcagcacg uaaauauugg cg 22

<210> SEQ ID NO: 90

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 90

uggaauguaa agaaguaugu au 22

<210> SEQ ID NO: 91

<211> LENGTH: 24

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 91

uggcccugac ugaagaccag cagu 24

<210> SEQ ID NO: 92

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 92

gcuauuucac gacaccaggg uu 22

<210> SEQ ID NO: 93

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 93

acuccauuug uuuugaugau gga 23

<210> SEQ ID NO: 94

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 94

caaaaaccac aguuucuuuu gc 22

<210> SEQ ID NO: 95

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 95

caaaguuuaa gauccuugaa gu 22

<210> SEQ ID NO: 96

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 96

aaaaguaauc gcgguuuuug uc 22

<210> SEQ ID NO: 97

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 97

gccccugggc cuauccuaga a 21

<210> SEQ ID NO: 98

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 98

gcccaaaggu gaauuuuuug gg 22

<210> SEQ ID NO: 99

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 99

guccaguuuu cccaggaauc ccu 23

<210> SEQ ID NO: 100

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 100

caaagugcuu acagugcagg uag 23

<210> SEQ ID NO: 101

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 101

uguaaacauc cuacacucag cu 22

<210> SEQ ID NO: 102

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 102

cuauacaauc uauugccuuc cc 22

<210> SEQ ID NO: 103

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 103

uuuucaacuc uaaugggaga ga 22

<210> SEQ ID NO: 104

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 104

cuuuuugcgg ucugggcuug c 21

<210> SEQ ID NO: 105

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 105

ucguggccug gucuccauua u 21

<210> SEQ ID NO: 106

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 106

ccgcacugug gguacuugcu gc 22

<210> SEQ ID NO: 107

<211> LENGTH: 24

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 107

gaccuggaca uguuugugcc cagu 24

<210> SEQ ID NO: 108

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 108

caaucagcaa guauacugcc cu 22

<210> SEQ ID NO: 109

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 109

aauggcgcca cuaggguugu g 21

<210> SEQ ID NO: 110

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 110

aggcauugac uucucacuag cu 22

<210> SEQ ID NO: 111

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 111

acuguaguau gggcacuucc ag 22

<210> SEQ ID NO: 112

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 112

caaaacguga ggcgcugcua u 21

<210> SEQ ID NO: 113

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 113

aucgugcauc ccuuuagagu gu 22

<210> SEQ ID NO: 114

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 114

ucuauacaga cccuggcuuu uc 22

<210> SEQ ID NO: 115

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 115

acaguagucu gcacauuggu ua 22

<210> SEQ ID NO: 116

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 116

guugugucag uuuaucaaac 20

<210> SEQ ID NO: 117

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 117

uaguagaccg uauagcguac g 21

<210> SEQ ID NO: 118

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 118

aucacauugc cagggauuac c 21

<210> SEQ ID NO: 119

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 119

uugggacaua cuuaugcuaa a 21

<210> SEQ ID NO: 120

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 120

uggcagugua uuguuagcug gu 22

<210> SEQ ID NO: 121

<211> LENGTH: 19

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 121

aaaaacugua auuacuuuu 19

<210> SEQ ID NO: 122

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 122

ugugucacuc gaugaccacu gu 22

<210> SEQ ID NO: 123

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 123

cacacacugc aauuacuuuu gc 22

<210> SEQ ID NO: 124

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 124

acccgucccg uucguccccg ga 22

<210> SEQ ID NO: 125

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 125

uccugcgcgu cccagaugcc c 21

<210> SEQ ID NO: 126

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 126

ugaguaccgc caugucuguu ggg 23

<210> SEQ ID NO: 127

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 127

ccuaguaggu guccaguaag ugu 23

<210> SEQ ID NO: 128

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 128

agguuacccg agcaacuuug cau 23

<210> SEQ ID NO: 129

<211> LENGTH: 24

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 129

uuuggcaaug guagaacuca cacu 24

<210> SEQ ID NO: 130

<211> LENGTH: 25

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 130

ggcggaggga aguagguccg uuggu 25

<210> SEQ ID NO: 131

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 131

augaccuaug aauugacaga c 21

<210> SEQ ID NO: 132

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 132

gugugcggaa augcuucugc ua 22

<210> SEQ ID NO: 133

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 133

uguaaacauc cccgacugga ag 22

<210> SEQ ID NO: 134

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 134

cuccugacuc cagguccugu gu 22

<210> SEQ ID NO: 135

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 135

accuggcaua caauguagau uu 22

<210> SEQ ID NO: 136

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 136

caaucacuaa cuccacugcc au 22

<210> SEQ ID NO: 137

<211> LENGTH: 25

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 137

aggcaccagc caggcauugc ucagc 25

<210> SEQ ID NO: 138

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 138

aacaggugac ugguuagaca a 21

<210> SEQ ID NO: 139

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 139

acuggacuug gagucagaag g 21

<210> SEQ ID NO: 140

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 140

ggugcagugc ugcaucucug gu 22

<210> SEQ ID NO: 141

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 141

ccucagggcu guagaacagg gcu 23

<210> SEQ ID NO: 142

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 142

gcuaguccug acucagccag u 21

<210> SEQ ID NO: 143

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 143

agaccuggcc cagaccucag c 21

<210> SEQ ID NO: 144

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 144

aggguguuuc ucucaucucu 20

<210> SEQ ID NO: 145

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 145

uguaaacauc cuacacucuc agc 23

<210> SEQ ID NO: 146

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 146

aaggagcuca cagucuauug ag 22

<210> SEQ ID NO: 147

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 147

aucacauugc cagggauuuc c 21

<210> SEQ ID NO: 148

<211> LENGTH: 19

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 148

ucuaggcugg uacugcuga 19

<210> SEQ ID NO: 149

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 149

guggcugcac ucacuuccuu c 21

<210> SEQ ID NO: 150

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 150

acuuuaacau ggaagugcuu uc 22

<210> SEQ ID NO: 151

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 151

guucaaaucc agaucuauaa c 21

<210> SEQ ID NO: 152

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 152

uggaguccag gaaucugcau uuu 23

<210> SEQ ID NO: 153

<211> LENGTH: 24

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 153

ccagacagaa uucuaugcac uuuc 24

<210> SEQ ID NO: 154

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 154

uaaauuucac cuuucugaga agg 23

<210> SEQ ID NO: 155

<211> LENGTH: 24

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 155

uggggagcug aggcucuggg ggug 24

<210> SEQ ID NO: 156

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 156

uagcaccauu ugaaaucagu guu 23

<210> SEQ ID NO: 157

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 157

accaggaggc ugaggccccu 20

<210> SEQ ID NO: 158

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 158

uaaggugcau cuagugcaga uag 23

<210> SEQ ID NO: 159

<211> LENGTH: 19

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 159

gugaggacuc gggaggugg 19

<210> SEQ ID NO: 160

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 160

caaauucgua ucuaggggaa ua 22

<210> SEQ ID NO: 161

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 161

accaucgacc guugauugua cc 22

<210> SEQ ID NO: 162

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 162

caugguucug ucaagcaccg cg 22

<210> SEQ ID NO: 163

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 163

aagugccgcc aucuuuugag ugu 23

<210> SEQ ID NO: 164

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 164

aucacacaaa ggcaacuuuu gu 22

<210> SEQ ID NO: 165

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 165

cagugguuuu acccuauggu ag 22

<210> SEQ ID NO: 166

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 166

cagugcaaua guauugucaa agc 23

<210> SEQ ID NO: 167

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 167

uacguagaua uauauguauu uu 22

<210> SEQ ID NO: 168

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 168

uucacauugu gcuacugucu gc 22

<210> SEQ ID NO: 169

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 169

uacccagagc augcagugug aa 22

<210> SEQ ID NO: 170

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 170

aacuggcccu caaagucccg cu 22

<210> SEQ ID NO: 171

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 171

ugccugucua cacuugcugu gc 22

<210> SEQ ID NO: 172

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 172

aaaucucugc aggcaaaugu ga 22

<210> SEQ ID NO: 173

<211> LENGTH: 17

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 173

uaauugcuuc cauguuu 17

<210> SEQ ID NO: 174

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 174

cucuagaggg aagcgcuuuc ug 22

<210> SEQ ID NO: 175

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 175

aaaaguaauu gcggucuuug gu 22

<210> SEQ ID NO: 176

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 176

auguauaaau guauacacac 20

<210> SEQ ID NO: 177

<211> LENGTH: 19

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 177

aagugugcag ggcacuggu 19

<210> SEQ ID NO: 178

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 178

ucccacguug uggcccagca g 21

<210> SEQ ID NO: 179

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 179

agcuacaucu ggcuacuggg u 21

<210> SEQ ID NO: 180

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 180

ugcuggauca gugguucgag uc 22

<210> SEQ ID NO: 181

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 181

ugcaacuuac cugagucauu ga 22

<210> SEQ ID NO: 182

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 182

ucucacacag aaaucgcacc cgu 23

<210> SEQ ID NO: 183

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 183

aagugcuguc auagcugagg uc 22

<210> SEQ ID NO: 184

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 184

aucccuugca ggggcuguug ggu 23

<210> SEQ ID NO: 185

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 185

auaagacgaa caaaagguuu gu 22

<210> SEQ ID NO: 186

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 186

ccaguauuaa cugugcugcu ga 22

<210> SEQ ID NO: 187

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 187

gcgacccaua cuugguuuca g 21

<210> SEQ ID NO: 188

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 188

ugcccugugg acucaguucu gg 22

<210> SEQ ID NO: 189

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 189

aaagugcuuc cuuuuagagg g 21

<210> SEQ ID NO: 190

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 190

aggcagugua uuguuagcug gc 22

<210> SEQ ID NO: 191

<211> LENGTH: 24

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 191

acaaagugcu ucccuuuaga gugu 24

<210> SEQ ID NO: 192

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 192

ugccuacuga gcugaaacac ag 22

<210> SEQ ID NO: 193

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 193

gaaagcgcuu cucuuuagag g 21

<210> SEQ ID NO: 194

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 194

aaaccugugu uguucaagag uc 22

<210> SEQ ID NO: 195

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 195

uauugcacau uacuaaguug ca 22

<210> SEQ ID NO: 196

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 196

cuagacugaa gcuccuugag g 21

<210> SEQ ID NO: 197

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 197

uagugcaaua uugcuuauag ggu 23

<210> SEQ ID NO: 198

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 198

uacaguacug ugauaacuga a 21

<210> SEQ ID NO: 199

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 199

aguuuugcag guuugcaucc agc 23

<210> SEQ ID NO: 200

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 200

uacugcagac aguggcaauc a 21

<210> SEQ ID NO: 201

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 201

uacaguauag augauguacu 20

<210> SEQ ID NO: 202

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 202

uacuccagag ggcgucacuc aug 23

<210> SEQ ID NO: 203

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 203

aguuaaugaa uccuggaaag u 21

<210> SEQ ID NO: 204

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 204

ugugcuugcu cgucccgccc gca 23

<210> SEQ ID NO: 205

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 205

auccgcgcuc ugacucucug cc 22

<210> SEQ ID NO: 206

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 206

ugucugcccg caugccugcc ucu 23

<210> SEQ ID NO: 207

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 207

uaaggcaccc uucugaguag a 21

<210> SEQ ID NO: 208

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 208

uauguaacau gguccacuaa cu 22

<210> SEQ ID NO: 209

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 209

ccugcagcga cuugauggcu ucc 23

<210> SEQ ID NO: 210

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 210

uucauuuggu auaaaccgcg auu 23

<210> SEQ ID NO: 211

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 211

uggguuccug gcaugcugau uu 22

<210> SEQ ID NO: 212

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 212

augggugaau uuguagaagg au 22

<210> SEQ ID NO: 213

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 213

uugcauaguc acaaaaguga uc 22

<210> SEQ ID NO: 214

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 214

aaagugcuuc cuuuuugagg g 21

<210> SEQ ID NO: 215

<211> LENGTH: 19

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 215

gugucugcuu ccuguggga 19

<210> SEQ ID NO: 216

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 216

cugcaaugua agcacuucuu ac 22

<210> SEQ ID NO: 217

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 217

ugcuaugcca acauauugcc au 22

<210> SEQ ID NO: 218

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 218

cagugccucg gcagugcagc cc 22

<210> SEQ ID NO: 219

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 219

uaugucugcu gaccaucacc uu 22

<210> SEQ ID NO: 220

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 220

caagcucgug ucuguggguc cg 22

<210> SEQ ID NO: 221

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 221

uaguacugug cauaucaucu au 22

<210> SEQ ID NO: 222

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 222

uauggcuuuu cauuccuaug uga 23

<210> SEQ ID NO: 223

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 223

uagaguuaca cccugggagu ua 22

<210> SEQ ID NO: 224

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 224

cuccguuugc cuguuucgcu g 21

<210> SEQ ID NO: 225

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 225

cuuagcaggu uguauuauca uu 22

<210> SEQ ID NO: 226

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 226

auugacacuu cugugaguag a 21

<210> SEQ ID NO: 227

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 227

uaauuuuaug uauaagcuag u 21

<210> SEQ ID NO: 228

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 228

aaacuacuga aaaucaaaga u 21

<210> SEQ ID NO: 229

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 229

aauaauacau gguugaucuu u 21

<210> SEQ ID NO: 230

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 230

uugaaaggcu auuucuuggu c 21

<210> SEQ ID NO: 231

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 231

ucacagugaa ccggucucuu u 21

<210> SEQ ID NO: 232

<211> LENGTH: 24

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 232

aauccuugga accuaggugu gagu 24

<210> SEQ ID NO: 233

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 233

aggaagcccu ggaggggcug gag 23

<210> SEQ ID NO: 234

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 234

cugcccuggc ccgagggacc ga 22

<210> SEQ ID NO: 235

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 235

caccaggcau uguggucucc 20

<210> SEQ ID NO: 236

<211> LENGTH: 25

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 236

ugggaacggg uuccggcaga cgcug 25

<210> SEQ ID NO: 237

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 237

uguaacagca acuccaugug ga 22

<210> SEQ ID NO: 238

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 238

uagcagcaca ucaugguuua ca 22

<210> SEQ ID NO: 239

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 239

aggggugcua ucugugauug a 21

<210> SEQ ID NO: 240

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 240

ucacaaguca ggcucuuggg ac 22

<210> SEQ ID NO: 241

<211> LENGTH: 17

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 241

uucaaguaau ucaggug 17

<210> SEQ ID NO: 242

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 242

ugugcgcagg gagaccucuc cc 22

<210> SEQ ID NO: 243

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 243

uuguacaugg uaggcuuuca uu 22

<210> SEQ ID NO: 244

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 244

ucaaaugcuc agacuccugu ggu 23

<210> SEQ ID NO: 245

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 245

uaacacuguc ugguaaagau gg 22

<210> SEQ ID NO: 246

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 246

aaccaucgac cguugagugg ac 22

<210> SEQ ID NO: 247

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 247

aacuggccua caaaguccca gu 22

<210> SEQ ID NO: 248

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 248

uaagugcuuc cauguuucag ugg 23

<210> SEQ ID NO: 249

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 249

agaggcuggc cgugaugaau uc 22

<210> SEQ ID NO: 250

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 250

aacaucacag caagucugug cu 22

<210> SEQ ID NO: 251

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 251

ucagcaaaca uuuauugugu gc 22

<210> SEQ ID NO: 252

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 252

aaaaguaauu gugguuuugg cc 22

<210> SEQ ID NO: 253

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 253

ugacaacuau ggaugagcuc u 21

<210> SEQ ID NO: 254

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 254

auucuaauuu cuccacgucu uu 22

<210> SEQ ID NO: 255

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 255

uagauaaaau auugguaccu g 21

<210> SEQ ID NO: 256

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 256

caaagaggaa ggucccauua c 21

<210> SEQ ID NO: 257

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 257

uuuccauagg ugaugaguca c 21

<210> SEQ ID NO: 258

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 258

cacaagguau ugguauuacc u 21

<210> SEQ ID NO: 259

<211> LENGTH: 19

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 259

aagcagcugc cucugaggc 19

<210> SEQ ID NO: 260

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 260

auaauacaug guuaaccucu uu 22

<210> SEQ ID NO: 261

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 261

uccauuacac uacccugccu cu 22

<210> SEQ ID NO: 262

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 262

ccaguggggc ugcuguuauc ug 22

<210> SEQ ID NO: 263

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 263

ugguuuaccg ucccacauac au 22

<210> SEQ ID NO: 264

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 264

cuccuauaug augccuuucu uc 22

<210> SEQ ID NO: 265

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 265

ugaaggucua cugugugcca gg 22

<210> SEQ ID NO: 266

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 266

caaaccacac ugugguguua ga 22

<210> SEQ ID NO: 267

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 267

aaagugcauc cuuuuagagu gu 22

<210> SEQ ID NO: 268

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 268

caagcucgcu ucuauggguc ug 22

<210> SEQ ID NO: 269

<211> LENGTH: 17

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 269

ucccaccgcu gccaccc 17

<210> SEQ ID NO: 270

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 270

cucuagaggg aagcgcuuuc ug 22

<210> SEQ ID NO: 271

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 271

gguccagagg ggagauaggu uc 22

<210> SEQ ID NO: 272

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 272

ugucuacuac uggagacacu gg 22

<210> SEQ ID NO: 273

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 273

cuuucaguca gauguuugcu gc 22

<210> SEQ ID NO: 274

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 274

cucaucugca aagaaguaag ug 22

<210> SEQ ID NO: 275

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 275

caagaaccuc aguugcuuuu gu 22

<210> SEQ ID NO: 276

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 276

uaugcauugu auuuuuaggu cc 22

<210> SEQ ID NO: 277

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 277

uauugcacuc gucccggccu cc 22

<210> SEQ ID NO: 278

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 278

ucgugcaucc cuuuagagug uu 22

<210> SEQ ID NO: 279

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 279

caaaacuggc aauuacuuuu gc 22

<210> SEQ ID NO: 280

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 280

uauaccucag uuuuaucagg ug 22

<210> SEQ ID NO: 281

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 281

caggucgucu ugcagggcuu cu 22

<210> SEQ ID NO: 282

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 282

auuccuagaa auuguucaua 20

<210> SEQ ID NO: 283

<211> LENGTH: 19

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 283

aguguggcuu ucuuagagc 19

<210> SEQ ID NO: 284

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 284

agaggauacc cuuuguaugu u 21

<210> SEQ ID NO: 285

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 285

cugguuucac augguggcuu ag 22

<210> SEQ ID NO: 286

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 286

gugacaucac auauacggca gc 22

<210> SEQ ID NO: 287

<211> LENGTH: 19

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 287

gggcgccugu gaucccaac 19

<210> SEQ ID NO: 288

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 288

cggcccgggc ugcugcuguu ccu 23

<210> SEQ ID NO: 289

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 289

cacuagauug ugagcuccug ga 22

<210> SEQ ID NO: 290

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 290

cuauacaguc uacugucuuu cc 22

<210> SEQ ID NO: 291

<211> LENGTH: 19

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 291

gaugaugcug cugaugcug 19

<210> SEQ ID NO: 292

<211> LENGTH: 18

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 292

ugaggcagua gauugaau 18

<210> SEQ ID NO: 293

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 293

cugccaauuc cauaggucac ag 22

<210> SEQ ID NO: 294

<211> LENGTH: 17

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 294

uaagugcuuc caugcuu 17

<210> SEQ ID NO: 295

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 295

uauguaacac gguccacuaa cc 22

<210> SEQ ID NO: 296

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 296

cagcagcaau ucauguuuug aa 22

<210> SEQ ID NO: 297

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 297

uaacugguug aacaacugaa cc 22

<210> SEQ ID NO: 298

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 298

guucucccaa cguaagccca gc 22

<210> SEQ ID NO: 299

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 299

cuuaugcaag auucccuucu ac 22

<210> SEQ ID NO: 300

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 300

aaagugcauc cuuuuagagg uu 22

<210> SEQ ID NO: 301

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 301

uaggacacau ggucuacuuc u 21

<210> SEQ ID NO: 302

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 302

cugaagcuca gagggcucug au 22

<210> SEQ ID NO: 303

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 303

ugcaggacca agaugagccc u 21

<210> SEQ ID NO: 304

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 304

accguggcuu ucgauuguua cu 22

<210> SEQ ID NO: 305

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 305

gugcauugcu guugcauugc 20

<210> SEQ ID NO: 306

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 306

aaaacgguga gauuuuguuu u 21

<210> SEQ ID NO: 307

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 307

auggagauag auauagaaau 20

<210> SEQ ID NO: 308

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 308

aaggagcuua caaucuagcu ggg 23

<210> SEQ ID NO: 309

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 309

cacuggcucc uuucugggua ga 22

<210> SEQ ID NO: 310

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 310

acaaagugcu ucccuuuaga gu 22

<210> SEQ ID NO: 311

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 311

augcaccugg gcaaggauuc ug 22

<210> SEQ ID NO: 312

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 312

gaaaucaagc gugggugaga cc 22

<210> SEQ ID NO: 313

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 313

caaagaauuc uccuuuuggg cu 22

<210> SEQ ID NO: 314

<211> LENGTH: 19

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 314

ugagcugcug uaccaaaau 19

<210> SEQ ID NO: 315

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 315

uucaaguaau ccaggauagg cu 22

<210> SEQ ID NO: 316

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 316

augguacccu ggcauacuga gu 22

<210> SEQ ID NO: 317

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 317

uucccuuugu cauccuucgc cu 22

<210> SEQ ID NO: 318

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 318

uuugaggcua cagugagaug ug 22

<210> SEQ ID NO: 319

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 319

ccaccaccgu gucugacacu u 21

<210> SEQ ID NO: 320

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 320

ugcaacgaac cugagccacu ga 22

<210> SEQ ID NO: 321

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 321

agagaagaag aucagccugc a 21

<210> SEQ ID NO: 322

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 322

ucugcagggu uugcuuugag 20

<210> SEQ ID NO: 323

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 323

uuauugcuua agaauacgcg uag 23

<210> SEQ ID NO: 324

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 324

aaucauacac gguugaccua uu 22

<210> SEQ ID NO: 325

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 325

aggguaagcu gaaccucuga u 21

<210> SEQ ID NO: 326

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 326

gugaacgggc gccaucccga gg 22

<210> SEQ ID NO: 327

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 327

aauugcacgg uauccaucug ua 22

<210> SEQ ID NO: 328

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 328

aaaaccgucu aguuacaguu gu 22

<210> SEQ ID NO: 329

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 329

agaguugagu cuggacgucc cg 22

<210> SEQ ID NO: 330

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 330

ccacaccgua ucugacacuu u 21

<210> SEQ ID NO: 331

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 331

cucaguagcc aguguagauc cu 22

<210> SEQ ID NO: 332

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 332

cacauuacac ggucgaccuc u 21

<210> SEQ ID NO: 333

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 333

aucauagagg aaaauccaug uu 22

<210> SEQ ID NO: 334

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 334

ccauggaucu ccaggugggu 20

<210> SEQ ID NO: 335

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 335

gaacgcgcuu cccuauagag ggu 23

<210> SEQ ID NO: 336

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 336

acuuaaacgu ggauguacuu gcu 23

<210> SEQ ID NO: 337

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 337

agagcuuagc ugauugguga ac 22

<210> SEQ ID NO: 338

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 338

agaccauggg uucucauugu 20

<210> SEQ ID NO: 339

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 339

uacucaaaaa gcugucaguc a 21

<210> SEQ ID NO: 340

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 340

guagauucuc cuucuaugag ua 22

<210> SEQ ID NO: 341

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 341

aaacucuacu uguccuucug agu 23

<210> SEQ ID NO: 342

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 342

gagggucuug ggagggaugu gac 23

<210> SEQ ID NO: 343

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 343

ccucccacac ccaaggcuug ca 22

<210> SEQ ID NO: 344

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 344

aacauucauu gcugucggug ggu 23

<210> SEQ ID NO: 345

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 345

aacgcacuuc ccuuuagagu gu 22

<210> SEQ ID NO: 346

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 346

ucaguaaaug uuuauuagau ga 22

<210> SEQ ID NO: 347

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 347

auaaagcuag auaaccgaaa gu 22

<210> SEQ ID NO: 348

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 348

ggggagcugu ggaagcagua 20

<210> SEQ ID NO: 349

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 349

ugaguuggcc aucugaguga g 21

<210> SEQ ID NO: 350

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 350

acuugggcac ugaaacaaug ucc 23

<210> SEQ ID NO: 351

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 351

uaauacugcc ugguaaugau ga 22

<210> SEQ ID NO: 352

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 352

uaugugccuu uggacuacau cg 22

<210> SEQ ID NO: 353

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 353

uggugguuua caaaguaauu ca 22

<210> SEQ ID NO: 354

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 354

acucaaaaug ggggcgcuuu cc 22

<210> SEQ ID NO: 355

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 355

ccucugaaau ucaguucuuc ag 22

<210> SEQ ID NO: 356

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 356

aacgccauua ucacacuaaa ua 22

<210> SEQ ID NO: 357

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 357

uugggaucau uuugcaucca ua 22

<210> SEQ ID NO: 358

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 358

uggcucaguu cagcaggaac ag 22

<210> SEQ ID NO: 359

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 359

ucaggcucag uccccucccg au 22

<210> SEQ ID NO: 360

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 360

ucauagcccu guacaaugcu gcu 23

<210> SEQ ID NO: 361

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 361

uauguaauau gguccacauc uu 22

<210> SEQ ID NO: 362

<211> LENGTH: 18

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 362

uucacaggga ggugucau 18

<210> SEQ ID NO: 363

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 363

uacugcagac guggcaauca ug 22

<210> SEQ ID NO: 364

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 364

gcaggaacuu gugagucucc u 21

<210> SEQ ID NO: 365

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 365

gaugagcuca uuguaauaug ag 22

<210> SEQ ID NO: 366

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 366

agaucgaccg uguuauauuc gc 22

<210> SEQ ID NO: 367

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 367

guguugaaac aaucucuacu g 21

<210> SEQ ID NO: 368

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 368

ucugcucaua ccccaugguu ucu 23

<210> SEQ ID NO: 369

<211> LENGTH: 18

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 369

ugcuuccuuu cagagggu 18

<210> SEQ ID NO: 370

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 370

aaagugcuuc cuuuuagagg gu 22

<210> SEQ ID NO: 371

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 371

caacuagacu gugagcuucu ag 22

<210> SEQ ID NO: 372

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 372

agagucuugu gaugucuugc 20

<210> SEQ ID NO: 373

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 373

cuacaaaggg aagcccuuuc 20

<210> SEQ ID NO: 374

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 374

cacucagccu ugagggcacu uuc 23

<210> SEQ ID NO: 375

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 375

cuuaucagau uguauuguaa uu 22

<210> SEQ ID NO: 376

<211> LENGTH: 25

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 376

cuagugaggg acagaaccag gauuc 25

<210> SEQ ID NO: 377

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 377

uguucaugua gauguuuaag c 21

<210> SEQ ID NO: 378

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 378

auauaugaug acuuagcuuu u 21

<210> SEQ ID NO: 379

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 379

cuccagaggg augcacuuuc u 21

<210> SEQ ID NO: 380

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 380

caucuuaccg gacagugcug ga 22

<210> SEQ ID NO: 381

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 381

uggguggucu ggagauuugu gc 22

<210> SEQ ID NO: 382

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 382

aaagugcugc gacauuugag cgu 23

<210> SEQ ID NO: 383

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 383

aaaaguaauu gcgaguuuua cc 22

<210> SEQ ID NO: 384

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 384

aaaaguacuu gcggauuuug cu 22

<210> SEQ ID NO: 385

<211> LENGTH: 18

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 385

uugagaagga ggcugcug 18

<210> SEQ ID NO: 386

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 386

caagucuuau uugagcaccu guu 23

<210> SEQ ID NO: 387

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 387

gcgacccacu cuugguuucc a 21

<210> SEQ ID NO: 388

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 388

uagguaguuu ccuguuguug gg 22

<210> SEQ ID NO: 389

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 389

caauuuagug ugugugauau uu 22

<210> SEQ ID NO: 390

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 390

gugcauugua guugcauugc a 21

<210> SEQ ID NO: 391

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 391

aaaaguaauu gugguuuuug cc 22

<210> SEQ ID NO: 392

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 392

agucauugga ggguuugagc ag 22

<210> SEQ ID NO: 393

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 393

uggauuucuu ugugaaucac ca 22

<210> SEQ ID NO: 394

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 394

ugauuguagc cuuuuggagu aga 23

<210> SEQ ID NO: 395

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 395

ccuauucuug auuacuuguu uc 22

<210> SEQ ID NO: 396

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 396

ucgugucuug uguugcagcc gg 22

<210> SEQ ID NO: 397

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 397

acaguagucu gcacauuggu ua 22

<210> SEQ ID NO: 398

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 398

aaucaugugc agugccaaua ug 22

<210> SEQ ID NO: 399

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 399

uaaggugcau cuagugcagu uag 23

<210> SEQ ID NO: 400

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 400

cuggauggcu ccuccauguc u 21

<210> SEQ ID NO: 401

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 401

ugauugguac gucugugggu ag 22

<210> SEQ ID NO: 402

<211> LENGTH: 27

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 402

cacuguaggu gauggugaga gugggca 27

<210> SEQ ID NO: 403

<211> LENGTH: 19

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 403

agcugucuga aaaugucuu 19

<210> SEQ ID NO: 404

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 404

uucacaagga ggugucauuu au 22

<210> SEQ ID NO: 405

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 405

agacuuccca uuugaaggug gc 22

<210> SEQ ID NO: 406

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 406

ucuuugguua ucuagcugua uga 23

<210> SEQ ID NO: 407

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 407

aagugccucc uuuuagagug uu 22

<210> SEQ ID NO: 408

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 408

uucccuuugu cauccuaugc cu 22

<210> SEQ ID NO: 409

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 409

uagcaccauu ugaaaucggu ua 22

<210> SEQ ID NO: 410

<211> LENGTH: 18

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 410

cgggcguggu gguggggg 18

<210> SEQ ID NO: 411

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 411

uggaguguga caaugguguu ug 22

<210> SEQ ID NO: 412

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 412

caacaaaucc cagucuaccu aa 22

<210> SEQ ID NO: 413

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 413

caggccauau ugugcugccu ca 22

<210> SEQ ID NO: 414

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 414

aacauucauu guugucggug ggu 23

<210> SEQ ID NO: 415

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 415

ugauugucca aacgcaauuc u 21

<210> SEQ ID NO: 416

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 416

uaagugcuuc cauguuugag ugu 23

<210> SEQ ID NO: 417

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 417

uggcaguguc uuagcugguu gu 22

<210> SEQ ID NO: 418

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 418

aauauaacac agauggccug u 21

<210> SEQ ID NO: 419

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 419

caauguuucc acagugcauc ac 22

<210> SEQ ID NO: 420

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 420

aaugcaccug ggcaaggauu ca 22

<210> SEQ ID NO: 421

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 421

ugguagacua uggaacguag g 21

<210> SEQ ID NO: 422

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 422

uuucaagcca gggggcguuu uuc 23

<210> SEQ ID NO: 423

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 423

cucuagaggg aagcacuuuc ug 22

<210> SEQ ID NO: 424

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 424

auauuaccau uagcucaucu uu 22

<210> SEQ ID NO: 425

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 425

auccuugcua ucugggugcu a 21

<210> SEQ ID NO: 426

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 426

aggcaagaug cuggcauagc u 21

<210> SEQ ID NO: 427

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 427

aacccguaga uccgaacuug ug 22

<210> SEQ ID NO: 428

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 428

gaggguuggg uggaggcucu cc 22

<210> SEQ ID NO: 429

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 429

gggggucccc ggugcucgga uc 22

<210> SEQ ID NO: 430

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 430

caacaccagu cgaugggcug u 21

<210> SEQ ID NO: 431

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 431

ggcagguucu cacccucucu agg 23

<210> SEQ ID NO: 432

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 432

uuuaggauaa gcuugacuuu ug 22

<210> SEQ ID NO: 433

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 433

uggaggagaa ggaaggugau g 21

<210> SEQ ID NO: 434

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 434

caaagguauu ugugguuuuu g 21

<210> SEQ ID NO: 435

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 435

agaauugugg cuggacaucu gu 22

<210> SEQ ID NO: 436

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 436

aaugcacccg ggcaaggauu cu 22

<210> SEQ ID NO: 437

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 437

uaagugcuuc cauguuuugg uga 23

<210> SEQ ID NO: 438

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 438

uuccuaugca uauacuucuu ug 22

<210> SEQ ID NO: 439

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 439

uggaauguaa ggaagugugu gg 22

<210> SEQ ID NO: 440

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 440

aaagugcuuc ucuuuggugg gu 22

<210> SEQ ID NO: 441

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 441

aaaaguaauu gcggauuuug cc 22

<210> SEQ ID NO: 442

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 442

gugucuuuug cucugcaguc a 21

<210> SEQ ID NO: 443

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 443

uguaaacauc cucgacugga ag 22

<210> SEQ ID NO: 444

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 444

ccccaccucc ucucuccuca g 21

<210> SEQ ID NO: 445

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 445

gaaggcgcuu cccuuuagag cg 22

<210> SEQ ID NO: 446

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 446

guggguacgg cccagugggg gg 22

<210> SEQ ID NO: 447

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 447

cguguauuug acaagcugag uu 22

<210> SEQ ID NO: 448

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 448

uccgagccug ggucucccuc uu 22

<210> SEQ ID NO: 449

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 449

cgaaaacagc aauuaccuuu gc 22

<210> SEQ ID NO: 450

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 450

aaaagcuggg uugagagggc ga 22

<210> SEQ ID NO: 451

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 451

uccaguacca cgugucaggg cca 23

<210> SEQ ID NO: 452

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 452

uuacaguugu ucaaccaguu acu 23

<210> SEQ ID NO: 453

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 453

gagcuuauuc auaaaagugc ag 22

<210> SEQ ID NO: 454

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 454

cuugguucag ggaggguccc ca 22

<210> SEQ ID NO: 455

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 455

acucuagcug ccaaaggcgc u 21

<210> SEQ ID NO: 456

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 456

uauucauuua uccccagccu aca 23

<210> SEQ ID NO: 457

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 457

cccagauaau ggcacucuca a 21

<210> SEQ ID NO: 458

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 458

aaaacuguaa uuacuuuugu ac 22

<210> SEQ ID NO: 459

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 459

caguaacaaa gauucauccu ugu 23

<210> SEQ ID NO: 460

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 460

ucggggauca ucaugucacg aga 23

<210> SEQ ID NO: 461

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 461

ugauauguuu gauauauuag gu 22

<210> SEQ ID NO: 462

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 462

augguuccgu caagcaccau gg 22

<210> SEQ ID NO: 463

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 463

acuguugcua auaugcaacu cu 22

<210> SEQ ID NO: 464

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 464

uuuugcgaug uguuccuaau au 22

<210> SEQ ID NO: 465

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 465

aauugcacuu uagcaauggu ga 22

<210> SEQ ID NO: 466

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 466

uaaggcacgc ggugaaugcc 20

<210> SEQ ID NO: 467

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 467

ugcaccaugg uugucugagc aug 23

<210> SEQ ID NO: 468

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 468

uaauacugcc ggguaaugau gga 23

<210> SEQ ID NO: 469

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 469

guccgcucgg cgguggccca 20

<210> SEQ ID NO: 470

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 470

cucuagaggg aagcacuuuc ug 22

<210> SEQ ID NO: 471

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 471

acaguagagg gaggaaucgc ag 22

<210> SEQ ID NO: 472

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 472

caaaaguaau uguggauuuu gu 22

<210> SEQ ID NO: 473

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 473

uagcuuauca gacugauguu ga 22

<210> SEQ ID NO: 474

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 474

ugguucuaga cuugccaacu a 21

<210> SEQ ID NO: 475

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 475

aggcagugua guuagcugau ugc 23

<210> SEQ ID NO: 476

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 476

uaauacuguc ugguaaaacc gu 22

<210> SEQ ID NO: 477

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 477

augcugacau auuuacuaga gg 22

<210> SEQ ID NO: 478

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 478

acugauuucu uuugguguuc ag 22

<210> SEQ ID NO: 479

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 479

gccugcuggg guggaaccug gu 22

<210> SEQ ID NO: 480

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 480

cuauacaauc uacugucuuu c 21

<210> SEQ ID NO: 481

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 481

caguuaucac agugcugaug cu 22

<210> SEQ ID NO: 482

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 482

uaaaguaaau augcaccaaa a 21

<210> SEQ ID NO: 483

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 483

uacugcauca ggaacugauu gga 23

<210> SEQ ID NO: 484

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 484

cucuagaggg aagcgcuuuc ug 22

<210> SEQ ID NO: 485

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 485

cuuucagucg gauguuuaca gc 22

<210> SEQ ID NO: 486

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 486

guguguggaa augcuucugc 20

<210> SEQ ID NO: 487

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 487

aaucguacag ggucauccac uu 22

<210> SEQ ID NO: 488

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 488

gacugacacc ucuuugggug aa 22

<210> SEQ ID NO: 489

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 489

uccuucauuc caccggaguc ug 22

<210> SEQ ID NO: 490

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 490

agugaaugau ggguucugac c 21

<210> SEQ ID NO: 491

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 491

uggaagacua gugauuuugu ugu 23

<210> SEQ ID NO: 492

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 492

agggcccccc cucaauccug u 21

<210> SEQ ID NO: 493

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 493

aggaugagca aagaaaguag auu 23

<210> SEQ ID NO: 494

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 494

ugguugacca uagaacaugc gc 22

<210> SEQ ID NO: 495

<211> LENGTH: 17

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 495

gugggggaga ggcuguc 17

<210> SEQ ID NO: 496

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 496

ucucugggcc ugugucuuag gc 22

<210> SEQ ID NO: 497

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 497

aacuggauca auuauaggag ug 22

<210> SEQ ID NO: 498

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 498

caucaucguc ucaaaugagu cu 22

<210> SEQ ID NO: 499

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 499

caucuuccag uacaguguug ga 22

<210> SEQ ID NO: 500

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 500

aucgugcauc cuuuuagagu gu 22

<210> SEQ ID NO: 501

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 501

ggcuagcaac agcgcuuacc u 21

<210> SEQ ID NO: 502

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 502

accuugccuu gcugcccggg cc 22

<210> SEQ ID NO: 503

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 503

uggugggcac agaaucugga cu 22

<210> SEQ ID NO: 504

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 504

aaacauucgc ggugcacuuc uu 22

<210> SEQ ID NO: 505

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 505

ucuucucugu uuuggccaug ug 22

<210> SEQ ID NO: 506

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 506

ccuauucuug guuacuugca cg 22

<210> SEQ ID NO: 507

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 507

aguauguucu uccaggacag aac 23

<210> SEQ ID NO: 508

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 508

uggacggaga acugauaagg gu 22

<210> SEQ ID NO: 509

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 509

aucauagagg aaaauccacg u 21

<210> SEQ ID NO: 510

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 510

cguguucaca gcggaccuug au 22

<210> SEQ ID NO: 511

<211> LENGTH: 24

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 511

agccuggaag cuggagccug cagu 24

<210> SEQ ID NO: 512

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 512

uggcagggag gcugggaggg g 21

<210> SEQ ID NO: 513

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 513

uugagaauga ugaaucauua gg 22

<210> SEQ ID NO: 514

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 514

cuauacaacc uacugccuuc cc 22

<210> SEQ ID NO: 515

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 515

ggagaaauua uccuuggugu gu 22

<210> SEQ ID NO: 516

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 516

aaagugcuuc ccuuuggacu gu 22

<210> SEQ ID NO: 517

<211> LENGTH: 19

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 517

ugggcguauc uguaugcua 19

<210> SEQ ID NO: 518

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 518

cuguaugccc ucaccgcuca 20

<210> SEQ ID NO: 519

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 519

cugacuguug ccguccucca g 21

<210> SEQ ID NO: 520

<211> LENGTH: 24

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 520

cugaagugau guguaacuga ucag 24

<210> SEQ ID NO: 521

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 521

caaagugcug uucgugcagg uag 23

<210> SEQ ID NO: 522

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 522

agggcuuagc ugcuugugag ca 22

<210> SEQ ID NO: 523

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 523

aggaauguuc cuucuuugcc 20

<210> SEQ ID NO: 524

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 524

acacagggcu guugugaaga cu 22

<210> SEQ ID NO: 525

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 525

gaaggcgcuu cccuuuggag u 21

<210> SEQ ID NO: 526

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 526

uaauccuugc uaccugggug aga 23

<210> SEQ ID NO: 527

<211> LENGTH: 24

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 527

agccugauua aacacaugcu cuga 24

<210> SEQ ID NO: 528

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 528

acugcauuau gagcacuuaa ag 22

<210> SEQ ID NO: 529

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 529

ggaggggucc cgcacuggga gg 22

<210> SEQ ID NO: 530

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 530

aucgggaaug ucguguccgc cc 22

<210> SEQ ID NO: 531

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 531

gagugccuuc uuuuggagcg uu 22

<210> SEQ ID NO: 532

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 532

agagguugcc cuuggugaau uc 22

<210> SEQ ID NO: 533

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 533

agacccuggu cugcacucua uc 22

<210> SEQ ID NO: 534

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 534

caaaaaucuc aauuacuuuu gc 22

<210> SEQ ID NO: 535

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 535

uaaagagccc uguggagaca 20

<210> SEQ ID NO: 536

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 536

agcugguguu gugaaucagg ccg 23

<210> SEQ ID NO: 537

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 537

ugucuugcag gccgucaugc a 21

<210> SEQ ID NO: 538

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 538

ugaaacauac acgggaaacc uc 22

<210> SEQ ID NO: 539

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 539

uugcauaugu aggauguccc au 22

<210> SEQ ID NO: 540

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 540

cuaauaguau cuaccacaau aaa 23

<210> SEQ ID NO: 541

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 541

aaucauacag ggacauccag uu 22

<210> SEQ ID NO: 542

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 542

ucuggcuccg ugucuucacu ccc 23

<210> SEQ ID NO: 543

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 543

uauacaaggg cagacucucu cu 22

<210> SEQ ID NO: 544

<211> LENGTH: 27

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 544

auugaucauc gacacuucga acgcaau 27

<210> SEQ ID NO: 545

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 545

ucggauccgu cugagcuugg cu 22

<210> SEQ ID NO: 546

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 546

uccuguacug agcugccccg ag 22

<210> SEQ ID NO: 547

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 547

ucagugcacu acagaacuuu gu 22

<210> SEQ ID NO: 548

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 548

ugugagguug gcauuguugu cu 22

<210> SEQ ID NO: 549

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 549

aaaaguauuu gcggguuuug uc 22

<210> SEQ ID NO: 550

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 550

cauaaaguag aaagcacuac u 21

<210> SEQ ID NO: 551

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 551

uuaauaucgg acaaccauug u 21

<210> SEQ ID NO: 552

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 552

uaaugccccu aaaaauccuu au 22

<210> SEQ ID NO: 553

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 553

cacccguaga accgaccuug cg 22

<210> SEQ ID NO: 554

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 554

caucuuacug ggcagcauug ga 22

<210> SEQ ID NO: 555

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 555

uaacacuguc ugguaacgau gu 22

<210> SEQ ID NO: 556

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 556

aaagcgcuuc ccuucagagu g 21

<210> SEQ ID NO: 557

<211> LENGTH: 25

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 557

gcugggcagg gcuucugagc uccuu 25

<210> SEQ ID NO: 558

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 558

gugaauuacc gaagggccau aa 22

<210> SEQ ID NO: 559

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 559

ucagugcauc acagaacuuu gu 22

<210> SEQ ID NO: 560

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 560

agcagcauug uacagggcua uga 23

<210> SEQ ID NO: 561

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 561

ccaaaacugc aguuacuuuu gc 22

<210> SEQ ID NO: 562

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 562

cccggagcca ggaugcagcu c 21

<210> SEQ ID NO: 563

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 563

uauagggauu ggagccgugg cg 22

<210> SEQ ID NO: 564

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 564

agaucagaag gugauugugg cu 22

<210> SEQ ID NO: 565

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 565

ucugcccccu ccgcugcugc ca 22

<210> SEQ ID NO: 566

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 566

gaagugcuuc gauuuugggg ugu 23

<210> SEQ ID NO: 567

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 567

acucaaacug ugggggcacu 20

<210> SEQ ID NO: 568

<211> LENGTH: 24

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 568

agcagaagca gggagguucu ccca 24

<210> SEQ ID NO: 569

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 569

uuugugaccu gguccacuaa cc 22

<210> SEQ ID NO: 570

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 570

acuucaccug guccacuagc cgu 23

<210> SEQ ID NO: 571

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 571

caaagcgcuu cucuuuagag ugu 23

<210> SEQ ID NO: 572

<211> LENGTH: 24

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 572

ucagaacaaa ugccgguucc caga 24

<210> SEQ ID NO: 573

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 573

acuuguaugc uagcucaggu ag 22

<210> SEQ ID NO: 574

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 574

uugugucaau augcgaugau gu 22

<210> SEQ ID NO: 575

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 575

cacugugucc uuucugcgua g 21

<210> SEQ ID NO: 576

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 576

aaauuauugu acaucggaug ag 22

<210> SEQ ID NO: 577

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 577

aagaugugga aaaauuggaa uc 22

<210> SEQ ID NO: 578

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 578

ucuuguguuc ucuagaucag u 21

<210> SEQ ID NO: 579

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 579

gacuauagaa cuuucccccu ca 22

<210> SEQ ID NO: 580

<211> LENGTH: 18

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 580

aucccaccuc ugccacca 18

<210> SEQ ID NO: 581

<211> LENGTH: 17

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 581

ucgccuccuc cucuccc 17

<210> SEQ ID NO: 582

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 582

gaacggcuuc auacaggagu u 21

<210> SEQ ID NO: 583

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 583

uuuggucccc uucaaccagc ua 22

<210> SEQ ID NO: 584

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 584

ggguggggau uuguugcauu ac 22

<210> SEQ ID NO: 585

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 585

caagcuugua ucuauaggua ug 22

<210> SEQ ID NO: 586

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 586

ugagaaccac gucugcucug ag 22

<210> SEQ ID NO: 587

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 587

uugugcuuga ucuaaccaug u 21

<210> SEQ ID NO: 588

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 588

caagucacua gugguuccgu u 21

<210> SEQ ID NO: 589

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 589

ccaauauuac ugugcugcuu ua 22

<210> SEQ ID NO: 590

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 590

cagugcaaug auauugucaa agc 23

<210> SEQ ID NO: 591

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 591

ugauauguuu gauauugggu u 21

<210> SEQ ID NO: 592

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 592

uuuguucguu cggcucgcgu ga 22

<210> SEQ ID NO: 593

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 593

uagcaaaaac ugcaguuacu uu 22

<210> SEQ ID NO: 594

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 594

aggggcuggc uuuccucugg uc 22

<210> SEQ ID NO: 595

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 595

caaagugccu cccuuuagag ug 22

<210> SEQ ID NO: 596

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 596

uaaaucccau ggugccuucu ccu 23

<210> SEQ ID NO: 597

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 597

guagaggaga uggcgcaggg 20

<210> SEQ ID NO: 598

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 598

acaggugagg uucuugggag cc 22

<210> SEQ ID NO: 599

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 599

cuguugccac uaaccucaac cu 22

<210> SEQ ID NO: 600

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 600

cucuagaggg aagcacuuuc ug 22

<210> SEQ ID NO: 601

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 601

aaaguucuga gacacuccga cu 22

<210> SEQ ID NO: 602

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 602

uaacagucuc cagucacggc c 21

<210> SEQ ID NO: 603

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 603

cgucaacacu ugcugguuuc cu 22

<210> SEQ ID NO: 604

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 604

ugaguauuac auggccaauc uc 22

<210> SEQ ID NO: 605

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 605

ucaaaacuga ggggcauuuu cu 22

<210> SEQ ID NO: 606

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 606

aaaaacugag acuacuuuug ca 22

<210> SEQ ID NO: 607

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 607

ucuaguaaga guggcagucg a 21

<210> SEQ ID NO: 608

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 608

cccugugccc ggcccacuuc ug 22

<210> SEQ ID NO: 609

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 609

uuaugguuug ccugggacug ag 22

<210> SEQ ID NO: 610

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 610

auguagggcu aaaagccaug gg 22

<210> SEQ ID NO: 611

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 611

uuaggccgca gaucugggug a 21

<210> SEQ ID NO: 612

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 612

uucaacgggu auuuauugag ca 22

<210> SEQ ID NO: 613

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 613

uuuggucccc uucaaccagc ug 22

<210> SEQ ID NO: 614

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 614

gucauacacg gcucuccucu cu 22

<210> SEQ ID NO: 615

<211> LENGTH: 25

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 615

aaaggauucu gcugucgguc ccacu 25

<210> SEQ ID NO: 616

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 616

auauaauaca accugcuaag ug 22

<210> SEQ ID NO: 617

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 617

aacacaccug guuaaccucu uu 22

<210> SEQ ID NO: 618

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 618

aagacgggag gaaagaaggg ag 22

<210> SEQ ID NO: 619

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 619

aggcagcggg guguagugga ua 22

<210> SEQ ID NO: 620

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 620

cugcgcaagc uacugccuug cu 22

<210> SEQ ID NO: 621

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 621

ccaguuaccg cuuccgcuac cgc 23

<210> SEQ ID NO: 622

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 622

cagugcaaug augaaagggc au 22

<210> SEQ ID NO: 623

<211> LENGTH: 18

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 623

gucccuguuc aggcgcca 18

<210> SEQ ID NO: 624

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 624

ucaccagccc uguguucccu ag 22

<210> SEQ ID NO: 625

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 625

cucuagaggg aagcgcuuuc ug 22

<210> SEQ ID NO: 626

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 626

ugagccccug ugccgccccc ag 22

<210> SEQ ID NO: 627

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 627

gucagcggag gaaaagaaac u 21

<210> SEQ ID NO: 628

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 628

cggcaacaag aaacugccug ag 22

<210> SEQ ID NO: 629

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 629

cuggagauau ggaagagcug ugu 23

<210> SEQ ID NO: 630

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 630

cuuggcaccu agcaagcacu ca 22

<210> SEQ ID NO: 631

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 631

ugagcuaaau gugugcuggg a 21

<210> SEQ ID NO: 632

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 632

cacgcucaug cacacaccca ca 22

<210> SEQ ID NO: 633

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 633

ucguuugccu uuuucugcuu 20

<210> SEQ ID NO: 634

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 634

acagauucga uucuagggga au 22

<210> SEQ ID NO: 635

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 635

uaaucucagc uggcaacugu ga 22

<210> SEQ ID NO: 636

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 636

ggauaucauc auauacugua ag 22

<210> SEQ ID NO: 637

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 637

gggguuccug gggaugggau uu 22

<210> SEQ ID NO: 638

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 638

uuaagacuug cagugauguu u 21

<210> SEQ ID NO: 639

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 639

uauggcacug guagaauuca cu 22

<210> SEQ ID NO: 640

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 640

caaccuggag gacuccaugc ug 22

<210> SEQ ID NO: 641

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 641

gcaaagcaca cggccugcag aga 23

<210> SEQ ID NO: 642

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 642

cuguacaggc cacugccuug c 21

<210> SEQ ID NO: 643

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 643

ucacuccucu ccucccgucu u 21

<210> SEQ ID NO: 644

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 644

acagcaggca cagacaggca gu 22

<210> SEQ ID NO: 645

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 645

uaggcagugu cauuagcuga uug 23

<210> SEQ ID NO: 646

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 646

acuuuaacau ggaggcacuu gc 22

<210> SEQ ID NO: 647

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 647

gaaguuguuc gugguggauu cg 22

<210> SEQ ID NO: 648

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 648

acccuaucaa uauugucucu gc 22

<210> SEQ ID NO: 649

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 649

gugccagcug caguggggga g 21

<210> SEQ ID NO: 650

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 650

agagguauag ggcaugggaa 20

<210> SEQ ID NO: 651

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 651

auucugcauu uuuagcaagu uc 22

<210> SEQ ID NO: 652

<211> LENGTH: 19

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 652

ugucucugcu gggguuucu 19

<210> SEQ ID NO: 653

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 653

cggcucuggg ucugugggga 20

<210> SEQ ID NO: 654

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 654

aaggcagggc ccccgcuccc c 21

<210> SEQ ID NO: 655

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 655

cuauacggcc uccuagcuuu cc 22

<210> SEQ ID NO: 656

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 656

uccuucugcu ccguccccca g 21

<210> SEQ ID NO: 657

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 657

ugcccuaaau gccccuucug gc 22

<210> SEQ ID NO: 658

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 658

aguauucugu accagggaag gu 22

<210> SEQ ID NO: 659

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 659

uucuccaaaa gggagcacuu uc 22

<210> SEQ ID NO: 660

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 660

aacuguuugc agaggaaacu ga 22

<210> SEQ ID NO: 661

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 661

ccuguucucc auuacuuggc uc 22

<210> SEQ ID NO: 662

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 662

aucuggaggu aagaagcacu uu 22

<210> SEQ ID NO: 663

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 663

uaugugggau gguaaaccgc uu 22

<210> SEQ ID NO: 664

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 664

uauacaaggg caagcucucu gu 22

<210> SEQ ID NO: 665

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 665

uuauaaagca augagacuga uu 22

<210> SEQ ID NO: 666

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 666

uaacagucua cagccauggu cg 22

<210> SEQ ID NO: 667

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 667

uguaguguuu ccuacuuuau gga 23

<210> SEQ ID NO: 668

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 668

acggguuagg cucuugggag cu 22

<210> SEQ ID NO: 669

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 669

cugggagaag gcuguuuacu cu 22

<210> SEQ ID NO: 670

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 670

gugagucucu aagaaaagag ga 22

<210> SEQ ID NO: 671

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 671

cggcggggac ggcgauuggu c 21

<210> SEQ ID NO: 672

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 672

ccuguugaag uguaaucccc a 21

<210> SEQ ID NO: 673

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 673

uuuugcaccu uuuggaguga a 21

<210> SEQ ID NO: 674

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 674

caucccuugc augguggagg g 21

<210> SEQ ID NO: 675

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 675

cggggcagcu caguacagga u 21

<210> SEQ ID NO: 676

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 676

aagccugccc ggcuccucgg g 21

<210> SEQ ID NO: 677

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 677

ugggucuuug cgggcgagau ga 22

<210> SEQ ID NO: 678

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 678

uccgguucuc agggcuccac c 21

<210> SEQ ID NO: 679

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 679

ugccuacuga gcugauauca gu 22

<210> SEQ ID NO: 680

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 680

aguuuugcag guuugcauuu ca 22

<210> SEQ ID NO: 681

<211> LENGTH: 18

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 681

gcaugggugg uucagugg 18

<210> SEQ ID NO: 682

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 682

auaagacgag caaaaagcuu gu 22

<210> SEQ ID NO: 683

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 683

uauggcuuuu uauuccuaug uga 23

<210> SEQ ID NO: 684

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 684

cuagguaugg ucccagggau cc 22

<210> SEQ ID NO: 685

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 685

aacauucaac cugucgguga gu 22

<210> SEQ ID NO: 686

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 686

augauccagg aaccugccuc u 21

<210> SEQ ID NO: 687

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 687

cgcaggggcc gggugcucac cg 22

<210> SEQ ID NO: 688

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 688

uggguuuacg uugggagaac u 21

<210> SEQ ID NO: 689

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 689

uacccuguag auccgaauuu gug 23

<210> SEQ ID NO: 690

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 690

aguggggaac ccuuccauga gg 22

<210> SEQ ID NO: 691

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 691

aggaccugcg ggacaagauu cuu 23

<210> SEQ ID NO: 692

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 692

uucucgagga aagaagcacu uuc 23

<210> SEQ ID NO: 693

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 693

uacucaggag aguggcaauc ac 22

<210> SEQ ID NO: 694

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 694

ccccagggcg acgcggcggg 20

<210> SEQ ID NO: 695

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 695

ucucuggagg gaagcacuuu cug 23

<210> SEQ ID NO: 696

<211> LENGTH: 25

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 696

gggcgacaaa gcaagacucu uucuu 25

<210> SEQ ID NO: 697

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 697

aggcggagac uugggcaauu g 21

<210> SEQ ID NO: 698

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 698

ugcggggcua gggcuaacag ca 22

<210> SEQ ID NO: 699

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 699

agugccugag ggaguaagag ccc 23

<210> SEQ ID NO: 700

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 700

uacuuggaaa ggcaucaguu g 21

<210> SEQ ID NO: 701

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 701

uuuagagacg gggucuugcu cu 22

<210> SEQ ID NO: 702

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 702

aggaggcagc gcucucagga c 21

<210> SEQ ID NO: 703

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 703

cgugccaccc uuuuccccag 20

<210> SEQ ID NO: 704

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 704

gaagugugcc gugguguguc u 21

<210> SEQ ID NO: 705

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 705

cggaugagca aagaaagugg uu 22

<210> SEQ ID NO: 706

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 706

agaaggaaau ugaauucauu ua 22

<210> SEQ ID NO: 707

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 707

gcaguccaug ggcauauaca c 21

<210> SEQ ID NO: 708

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 708

gcugacuccu aguccagggc uc 22

<210> SEQ ID NO: 709

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 709

uuuggcacua gcacauuuuu gcu 23

<210> SEQ ID NO: 710

<211> LENGTH: 18

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 710

cagggaggug aaugugau 18

<210> SEQ ID NO: 711

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 711

uucucaagga ggugucguuu au 22

<210> SEQ ID NO: 712

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 712

aaaaguaauu gcgguuuuug cc 22

<210> SEQ ID NO: 713

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 713

aggcggggcg ccgcgggacc gc 22

<210> SEQ ID NO: 714

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 714

aaaagcuggg uugagagggu 20

<210> SEQ ID NO: 715

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 715

aaaagcuggg uugagagggc aa 22

<210> SEQ ID NO: 716

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 716

uggugggccg cagaacaugu gc 22

<210> SEQ ID NO: 717

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 717

ccucugggcc cuuccuccag 20

<210> SEQ ID NO: 718

<211> LENGTH: 18

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 718

uccagugccc uccucucc 18

<210> SEQ ID NO: 719

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 719

cuggcccucu cugcccuucc gu 22

<210> SEQ ID NO: 720

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 720

ugagaacuga auuccauagg cu 22

<210> SEQ ID NO: 721

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 721

cgcgggugcu uacugacccu u 21

<210> SEQ ID NO: 722

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 722

ugagugccgg ugccugcccu g 21

<210> SEQ ID NO: 723

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 723

cucggcgcgg ggcgcgggcu cc 22

<210> SEQ ID NO: 724

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 724

uccagcauca gugauuuugu ug 22

<210> SEQ ID NO: 725

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 725

cgggucggag uuagcucaag cgg 23

<210> SEQ ID NO: 726

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 726

uggucuagga uuguuggagg ag 22

<210> SEQ ID NO: 727

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 727

uucauucggc uguccagaug ua 22

<210> SEQ ID NO: 728

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 728

ccaguccugu gccugccgcc u 21

<210> SEQ ID NO: 729

<211> LENGTH: 26

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 729

gugagggcau gcaggccugg augggg 26

<210> SEQ ID NO: 730

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 730

aucaacagac auuaauuggg cgc 23

<210> SEQ ID NO: 731

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 731

gcccgcgugu ggagccaggu gu 22

<210> SEQ ID NO: 732

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 732

cugguacagg ccugggggac ag 22

<210> SEQ ID NO: 733

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 733

cucucaccac ugcccuccca cag 23

<210> SEQ ID NO: 734

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 734

acugcaguga aggcacuugu ag 22

<210> SEQ ID NO: 735

<211> LENGTH: 19

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 735

aaaagcuggg uugagagga 19

<210> SEQ ID NO: 736

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 736

uacccuguag aaccgaauuu gug 23

<210> SEQ ID NO: 737

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 737

acuccagccc cacagccuca gc 22

<210> SEQ ID NO: 738

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 738

acuuacagac aagagccuug cuc 23

<210> SEQ ID NO: 739

<211> LENGTH: 24

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 739

aaagacauag gauagaguca ccuc 24

<210> SEQ ID NO: 740

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 740

uccgucucag uuacuuuaua gc 22

<210> SEQ ID NO: 741

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 741

acucaaaacc cuucagugac uu 22

<210> SEQ ID NO: 742

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 742

cuccagaggg aaguacuuuc u 21

<210> SEQ ID NO: 743

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 743

aagcauucuu ucauugguug g 21

<210> SEQ ID NO: 744

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 744

uugcucacug uucuucccua g 21

<210> SEQ ID NO: 745

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 745

cugggaggug gauguuuacu uc 22

<210> SEQ ID NO: 746

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 746

cuccuacaua uuagcauuaa ca 22

<210> SEQ ID NO: 747

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 747

gcuacuucac aacaccaggg cc 22

<210> SEQ ID NO: 748

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 748

aauccuuugu cccuggguga ga 22

<210> SEQ ID NO: 749

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 749

caacggaauc ccaaaagcag cug 23

<210> SEQ ID NO: 750

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 750

agcagcauug uacagggcua uca 23

<210> SEQ ID NO: 751

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 751

aucgcugcgg uugcgagcgc ugu 23

<210> SEQ ID NO: 752

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 752

caaagcgcuu cccuuuggag c 21

<210> SEQ ID NO: 753

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 753

uaaagugcug acagugcaga u 21

<210> SEQ ID NO: 754

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 754

aagcccuuac cccaaaaagc au 22

<210> SEQ ID NO: 755

<211> LENGTH: 18

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 755

acguuggcuc ugguggug 18

<210> SEQ ID NO: 756

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 756

ggcuacaaca caggacccgg gc 22

<210> SEQ ID NO: 757

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 757

ucccugagac ccuaacuugu ga 22

<210> SEQ ID NO: 758

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 758

gucccucucc aaaugugucu ug 22

<210> SEQ ID NO: 759

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 759

cuuucagucg gauguuugca gc 22

<210> SEQ ID NO: 760

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 760

ucuacagugc acgugucucc ag 22

<210> SEQ ID NO: 761

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 761

acucggcgug gcgucggucg ug 22

<210> SEQ ID NO: 762

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 762

cugggaucuc cggggucuug guu 23

<210> SEQ ID NO: 763

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 763

caugccuuga guguaggacc gu 22

<210> SEQ ID NO: 764

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 764

caacaaauca cagucugcca ua 22

<210> SEQ ID NO: 765

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 765

uagguaguuu cauguuguug gg 22

<210> SEQ ID NO: 766

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 766

uuagggcccu ggcuccaucu cc 22

<210> SEQ ID NO: 767

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 767

gcugcgcuug gauuucgucc cc 22

<210> SEQ ID NO: 768

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 768

agcuacauug ucugcugggu uuc 23

<210> SEQ ID NO: 769

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 769

agguugggau cgguugcaau gcu 23

<210> SEQ ID NO: 770

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 770

ucugggcaac aaagugagac cu 22

<210> SEQ ID NO: 771

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 771

cucuagaggg aagcacuuuc uc 22

<210> SEQ ID NO: 772

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 772

ugagcccugu ccucccgcag 20

<210> SEQ ID NO: 773

<211> LENGTH: 19

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 773

uggauuuuug gaucaggga 19

<210> SEQ ID NO: 774

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 774

uacgucaucg uugucaucgu ca 22

<210> SEQ ID NO: 775

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 775

ugagaccucu ggguucugag cu 22

<210> SEQ ID NO: 776

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 776

gaacgccugu ucuugccagg ugg 23

<210> SEQ ID NO: 777

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 777

cuucuugugc ucuaggauug u 21

<210> SEQ ID NO: 778

<211> LENGTH: 24

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 778

uugcagcugc cugggaguga cuuc 24

<210> SEQ ID NO: 779

<211> LENGTH: 24

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 779

uucuccaaaa gaaagcacuu ucug 24

<210> SEQ ID NO: 780

<211> LENGTH: 19

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 780

aggcacggug ucagcaggc 19

<210> SEQ ID NO: 781

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 781

aaccagcacc ccaacuuugg ac 22

<210> SEQ ID NO: 782

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 782

caaagcgcuc cccuuuagag gu 22

<210> SEQ ID NO: 783

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 783

cacccggcug ugugcacaug ugc 23

<210> SEQ ID NO: 784

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 784

aacauagagg aaauuccacg u 21

<210> SEQ ID NO: 785

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 785

ccaauauugg cugugcugcu cc 22

<210> SEQ ID NO: 786

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 786

cugcaaaggg aagcccuuuc 20

<210> SEQ ID NO: 787

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 787

guuugcacgg gugggccuug ucu 23

<210> SEQ ID NO: 788

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 788

gugggcgggg gcaggugugu g 21

<210> SEQ ID NO: 789

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 789

aguucuucag uggcaagcuu ua 22

<210> SEQ ID NO: 790

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 790

ucggccugac cacccacccc ac 22

<210> SEQ ID NO: 791

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 791

agggagggac gggggcugug c 21

<210> SEQ ID NO: 792

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 792

cugggagagg guuguuuacu cc 22

<210> SEQ ID NO: 793

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 793

cgucuuaccc agcaguguuu gg 22

<210> SEQ ID NO: 794

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 794

ccgucgccgc cacccgagcc g 21

<210> SEQ ID NO: 795

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 795

aggugguccg uggcgcguuc gc 22

<210> SEQ ID NO: 796

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 796

gugucugggc ggacagcugc 20

<210> SEQ ID NO: 797

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 797

gugaaauguu uaggaccacu ag 22

<210> SEQ ID NO: 798

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 798

uuuaacaugg ggguaccugc ug 22

<210> SEQ ID NO: 799

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 799

aacccguaga uccgaucuug ug 22

<210> SEQ ID NO: 800

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 800

ugagaacuga auuccauggg uu 22

<210> SEQ ID NO: 801

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 801

aauauuauac agucaaccuc u 21

<210> SEQ ID NO: 802

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 802

gaaagugcuu ccuuuuagag gc 22

<210> SEQ ID NO: 803

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 803

aaguucuguu auacacucag gc 22

<210> SEQ ID NO: 804

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 804

aacauucaac gcugucggug agu 23

<210> SEQ ID NO: 805

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 805

acagucugcu gagguuggag c 21

<210> SEQ ID NO: 806

<211> LENGTH: 24

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 806

ucccugagac ccuuuaaccu guga 24

<210> SEQ ID NO: 807

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 807

ucagugcaug acagaacuug g 21

<210> SEQ ID NO: 808

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 808

uucaccaccu ucuccaccca gc 22

<210> SEQ ID NO: 809

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 809

uucacagugg cuaaguucug c 21

<210> SEQ ID NO: 810

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 810

ccucuucccc uugucucucc ag 22

<210> SEQ ID NO: 811

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 811

aaacaaacau ggugcacuuc uu 22

<210> SEQ ID NO: 812

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 812

ugagaugaag cacuguagcu c 21

<210> SEQ ID NO: 813

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 813

aacacaccua uucaaggauu ca 22

<210> SEQ ID NO: 814

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 814

uggugcggag agggcccaca gug 23

<210> SEQ ID NO: 815

<211> LENGTH: 17

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 815

ucccuguucg ggcgcca 17

<210> SEQ ID NO: 816

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 816

ggagacgcgg cccuguugga gu 22

<210> SEQ ID NO: 817

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 817

acucuuuccc uguugcacua c 21

<210> SEQ ID NO: 818

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 818

ucacaccugc cucgcccccc 20

<210> SEQ ID NO: 819

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 819

uuuccggcuc gcgugggugu gu 22

<210> SEQ ID NO: 820

<211> LENGTH: 19

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 820

gagccaguug gacaggagc 19

<210> SEQ ID NO: 821

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 821

ugugacuggu ugaccagagg gg 22

<210> SEQ ID NO: 822

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 822

ccuggaaaca cugagguugu g 21

<210> SEQ ID NO: 823

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 823

agggacggga cgcggugcag ug 22

<210> SEQ ID NO: 824

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 824

uacccauugc auaucggagu ug 22

<210> SEQ ID NO: 825

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 825

cucuugaggg aagcacuuuc ugu 23

<210> SEQ ID NO: 826

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 826

acuggacuua gggucagaag gc 22

<210> SEQ ID NO: 827

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 827

acggugcugg auguggccuu u 21

<210> SEQ ID NO: 828

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 828

ugcccuuaaa ggugaaccca gu 22

<210> SEQ ID NO: 829

<211> LENGTH: 25

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 829

agggguggug uugggacagc uccgu 25

<210> SEQ ID NO: 830

<211> LENGTH: 17

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 830

ucauauugcu ucuuucu 17

<210> SEQ ID NO: 831

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 831

acgcccuucc cccccuucuu ca 22

<210> SEQ ID NO: 832

<211> LENGTH: 24

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 832

ugccuggguc ucuggccugc gcgu 24

<210> SEQ ID NO: 833

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 833

ucacuguuca gacaggcgga 20

<210> SEQ ID NO: 834

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 834

cagugcaaug uuaaaagggc au 22

<210> SEQ ID NO: 835

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 835

uuuugcaaua uguuccugaa ua 22

<210> SEQ ID NO: 836

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 836

ucuuggagua ggucauuggg ugg 23

<210> SEQ ID NO: 837

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 837

gaauguugcu cggugaaccc cu 22

<210> SEQ ID NO: 838

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 838

cugcaaaggg aagcccuuuc 20

<210> SEQ ID NO: 839

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 839

uccucuucuc ccuccuccca g 21

<210> SEQ ID NO: 840

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 840

cuuccucguc ugucugcccc 20

<210> SEQ ID NO: 841

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 841

ccucuagaug gaagcacugu cu 22

<210> SEQ ID NO: 842

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 842

cgggguuuug agggcgagau ga 22

<210> SEQ ID NO: 843

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 843

cuacaaaggg aagcacuuuc uc 22

<210> SEQ ID NO: 844

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 844

aguuaggauu aggucgugga a 21

<210> SEQ ID NO: 845

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 845

uagguuaucc guguugccuu cg 22

<210> SEQ ID NO: 846

<211> LENGTH: 24

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 846

acugggggcu uucgggcucu gcgu 24

<210> SEQ ID NO: 847

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 847

uuggccacaa uggguuagaa c 21

<210> SEQ ID NO: 848

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 848

uuaaugcuaa ucgugauagg ggu 23

<210> SEQ ID NO: 849

<211> LENGTH: 24

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 849

acuggcuagg gaaaaugauu ggau 24

<210> SEQ ID NO: 850

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 850

gcccuccgcc cgugcacccc g 21

<210> SEQ ID NO: 851

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 851

acggauguuu gagcaugugc ua 22

<210> SEQ ID NO: 852

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 852

cgcauccccu agggcauugg ugu 23

<210> SEQ ID NO: 853

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 853

aagcccuuac cccaaaaagu au 22

<210> SEQ ID NO: 854

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 854

agggggaaag uucuauaguc c 21

<210> SEQ ID NO: 855

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 855

cucuagaggg aagcgcuuuc ug 22

<210> SEQ ID NO: 856

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 856

accacugacc guugacugua cc 22

<210> SEQ ID NO: 857

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 857

cccaguguuu agacuaucug uuc 23

<210> SEQ ID NO: 858

<211> LENGTH: 21

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 858

uucacagugg cuaaguuccg c 21

<210> SEQ ID NO: 859

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 859

gaaagcgcuu cccuuugcug ga 22

<210> SEQ ID NO: 860

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 860

caggaugugg ucaaguguug uu 22

<210> SEQ ID NO: 861

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 861

uauugcacuu gucccggccu gu 22

<210> SEQ ID NO: 862

<211> LENGTH: 24

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 862

gcugguuuca uauggugguu uaga 24

<210> SEQ ID NO: 863

<211> LENGTH: 22

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 863

ucucccaacc cuuguaccag ug 22

<210> SEQ ID NO: 864

<211> LENGTH: 23

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 864

ucaagagcaa uaacgaaaaa ugu 23

<210> SEQ ID NO: 865

<211> LENGTH: 25

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 865

agggaucgcg ggcggguggc ggccu 25

<210> SEQ ID NO: 866

<211> LENGTH: 20

<212> TYPE: RNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 866

aaaguagcug uaccauuugc 20

<210> SEQ ID NO: 867

<211> LENGTH: 22

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 867

actccatcat ccaacatatc aa 22

<210> SEQ ID NO: 868

<211> LENGTH: 22

<212> TYPE: DNA

<213> ORGANISM: Homo sapiens

<400> SEQENCE: 868

aactatacaa cctactacct ca 22

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Patent Valuation

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20.03/100 Score

Market Attractiveness

It shows from an IP point of view how many competitors are active and innovations are made in the different technical fields of the company. On a company level, the market attractiveness is often also an indicator of how diversified a company is. Here we look into the commercial relevance of the market.

100.0/100 Score

Market Coverage

It shows the sizes of the market that is covered with the IP and in how many countries the IP guarantees protection. It reflects a market size that is potentially addressable with the invented technology/formulation with a legal protection which also includes a freedom to operate. Here we look into the size of the impacted market.

67.72/100 Score

Technology Quality

It shows the degree of innovation that can be derived from a company’s IP. Here we look into ease of detection, ability to design around and significance of the patented feature to the product/service.

40.08/100 Score

Assignee Score

It takes the R&D behavior of the company itself into account that results in IP. During the invention phase, larger companies are considered to assign a higher R&D budget on a certain technology field, these companies have a better influence on their market, on what is marketable and what might lead to a standard.

21.74/100 Score

Legal Score

It shows the legal strength of IP in terms of its degree of protecting effect. Here we look into claim scope, claim breadth, claim quality, stability and priority.

Citation

Patents Cited in This Cited by
Title Current Assignee Application Date Publication Date
miRNA fingerprint in the diagnosis of multiple sclerosis HUMMINGBIRD DIAGNOSTICS GMBH 07 June 2010 17 November 2015
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