SPLICE VARIANTS ASSOCIATED WITH NEOMORPHIC SF3B1 MUTANTS

Abstract
Splice variants associated with neomorphic SF3B1 mutations are described herein. This application also relates to methods of detecting the described splice variants, and uses for diagnosing cancer, evaluating modulators of SF3B1, and methods of treating cancer associated with mutations in SF3B1.
Description

The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. The ASCII copy, created on May 16, 2014, is named 12636.6-304_SL.txt and is 183 kilobytes in size.


RNA splicing, a highly regulated molecular event orchestrated by the spliceosome, results in the removal of intronic sequences from pre-mRNA to generate mature mRNA. Dysregulation of RNA splicing has been identified as a causative defect in several diseases. In addition, dysregulated splicing has been proposed to play an important role in tumorigenesis and resistance to therapy; however, the molecular causes of dysregulated splicing in cancer have remained elusive.


SF3B1 is a protein involved in RNA splicing. It forms part of the U2 snRNP complex which binds to the pre-mRNA at a region containing the branchpoint site and is involved in early recognition and stabilization of the spliceosome at the 3′ splice site (3′ ss). A thorough and systematic analysis of the effects of SF3B1 mutations is needed to define their effects on RNA splicing in cells and may lead to novel therapeutic approaches for SF3B1 mutant cancers.


The description provided herein demonstrates that certain SF3B1 mutations result in neomorphic activity with the production of known and novel splicing alterations. In addition, lineage-specific splicing aberrations were identified in chronic lymphocytic leukemia (CLL), melanoma, and breast cancer. Furthermore, treatment of SF3B1-mutant cancer cell lines, xenografts, and CLL patient samples with modulators of SF3B1 reduced aberrant splicing and induced tumor regression.


SUMMARY

The methods described herein involve detecting or quantifying the expression of one or more splice variants in a cell containing a neomorphic mutant SF3B1 protein. Various embodiments of the invention include detecting or quantifying splice variants to determine whether a patient has a cancer with one or more neomorphic SF3B1 mutations. Additional embodiments include measuring the amount of a splice variant to evaluate the effects of a compound on a mutant SF3B1 protein. Further embodiments include methods of treating a patient who has cancer cells with a neomorphic mutant SF3B1 protein.


Various embodiments encompass a method of detecting one or more splice variants selected from rows 1-790 of Table 1 in a biological sample, comprising:


a) providing a biological sample suspected of containing one or more splice variants;


b) contacting the biological sample with one or more nucleic acid probes capable of specifically hybridizing to the one or more splice variants, and


c) detecting the binding of the one or more probes to the one or more splice variants.


In some embodiments, the one or more nucleic acid probes capable of specifically hybridizing to the one or more splice variants each comprise a label. In some embodiments, the method of detecting one or more splice variants selected from rows 1-790 of Table 1 in a biological sample further comprises contacting the biological sample with one or more additional nucleic acid probes, wherein the additional probes are each labeled with a molecular barcode.


Embodiments further encompass a method of modulating the activity of a neomorphic mutant SF3B1 protein in a target cell, comprising applying an SF3B1-modulating compound to the target cell, wherein the target cell has been determined to express one or more aberrant splice variants selected from rows 1-790 of Table 1 at a level that is increased or decreased relative to the level in a cell not having the neomorphic mutant SF3B1 protein.


Embodiments also encompass a method for evaluating the ability of a compound to modulate the activity of a neomorphic mutant SF3B1 protein in a target cell, comprising the steps of:


a) providing a target cell having a mutant SF3B1 protein;


b) applying the compound to the target cell; and


c) measuring the expression level of one or more splice variants selected from row 1-790 of Table 1.


In some embodiments, the method for evaluating the ability of a compound to modulate the activity of a neomorphic mutant SF3B1 protein in a target cell further comprises the step of measuring the expression level of one or more splice variants selected from row 1-790 of Table 1 before step (b).


In some embodiments, the neomorphic mutant SF3B1 protein is selected from K700E, K666N, R625C, G742D, R625H, E622D, H662Q, K666T, K666E, K666R, G740E, Y623C, T663I, K741N, N626Y, T663P, H662R, G740V, D781E, or R625L. In some embodiments, the neomorphic mutant SF3B1 protein is selected from E622D, E622K, E622Q, E622V, Y623C, Y623H, Y623S, R625C, R625G, R625H, R625L, R625P, R625S, N626D, N626H, N626I, N626S, N626Y, H662D, H662L, H662Q, H662R, H662Y, T663I, T663P, K666E, K666M, K666N, K666Q, K666R, K666S, K666T, K700E, V701A, V701F, V701I, I704F, I704N, I704S, I704V, G740E, G740K, G740R, G740V, K741N, K741Q, K741T, G742D, D781E, D781G, or D781N.


In some embodiments, the step of measuring the expression level of one or more splice variants comprises using an assay to quantify nucleic acid selected from nucleic acid barcoding (e.g. NanoString®), RT-PCR, microarray, nucleic acid sequencing, nanoparticle probes (e.g. SmartFlare™), and in situ hybridization (e.g. RNAscope®).


In some embodiments, the step of measuring the expression level of one or more splice variants comprises measuring the number of copies of the one or more splice variant RNAs in the target cell.


In further embodiments, the compound is selected from a small molecule, an antibody, an antisense molecule, an aptamer, an RNA molecule, and a peptide. In further embodiments, the small molecule is selected from pladienolide and a pladienolide analog. In additional embodiments, the pladienolide analog is selected from pladienolide B, pladienolide D, E7107, a compound of formula 1:




embedded image


a compound of formula 2:




embedded image


a compound of formula 3:




embedded image


or a compound of formula 4:




embedded image


In some embodiments, the target cell is obtained from a patient suspected of having myelodysplastic syndrome, chronic lymphocytic leukemia, chronic myelomonocytic leukemia, or acute myeloid leukemia. In some embodiments, the target cell is obtained from a sample selected from blood or a blood fraction or is a cultured cell derived from a cell obtained from a sample chosen from blood or a blood fraction. In some embodiments, the target cell is a lymphocyte.


In further embodiments, the target cell is obtained from a solid tumor. In some embodiments, the target cell is a breast tissue cell, pancreatic cell, lung cell, or skin cell.


In some embodiments, one or more of the aberrant variants are selected from rows 1, 7, 9, 10, 13, 15, 16, 18, 21, 24, 27, 28, 30, 31, 33, 34, 48, 51, 62, 65, 66, 71, 72, 81, 84, 89, 91, 105, 107, 121, 135, 136, 152, 178, 235, 240, 247, 265, 267, 272, 276, 279, 282, 283, 286, 292, 295, 296, 298, 302, 306, 329, 330, 331, 343, 350, 355, 356, 360, 364, 372, 378, 390, 391, 423, 424, 425, 426, 431, 433, 438, 439, 443, 445, 447, 448, 451, 452, 458, 459, 460, 462, 468, 469, 472, 500, 508, 517, 519, 521, 524, 525, 527, 528, 530, 533, 536, 540, 543, 548, 545, 554, 556, 559, 571, 573, 580, 582, 583, 597, 601, 615, 617, 618, 639, 640, 654, 657, 666, 670, 680, 727, 730, 750, 758, 767, or 774 of Table 1.


In some embodiments, one or more of the aberrant variants are selected from rows 21, 31, 51, 81, 118, 279, 372, 401, 426, 443, 528, 543, 545, 548 or 566 of Table 1.


Embodiments further encompass a method for treating a patient with a neoplastic disorder, comprising administering a therapeutically effective amount of an SF3B1-modulating compound to the patient, wherein a cell from the patient has been determined to:

    • a) contain a neomorphic mutant SF3B1 protein; and
    • b) express one or more aberrant splice variants selected from rows 1-790 of Table 1 at a level that is increased or decreased relative to the level in a cell not having the neomorphic mutant SF3B1 protein.


Additional embodiments are set forth in the description which follows.


It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed.





BRIEF DESCRIPTION OF THE DRAWINGS


FIG. 1 is a schematic diagram depicting modes of alternative splicing.



FIG. 2 is a graph depicting levels of gene expression for abnormally spliced genes across different cancers in patient samples.



FIG. 3 is a schematic diagram showing the locations of certain neomorphic mutations in the SF3B1 protein and corresponding coding regions of the SF3B1 gene.



FIG. 4 is a graph depicting levels of aberrant splice variants detected in RNA isolated from pancreatic, lung cancer, and Nalm-6 isogenic cell lines using a NanoString® assay. Data are represented as the mean of three replicates.



FIG. 5 is a set of western blot images that confirm overexpression of SF3B1 proteins in 293FT cells.



FIG. 6 is a graph depicting levels of aberrant splice variants in RNA isolated from 293FT cells expressing wild type SF3B1 (SF3B1WT) or mutant SF3B1 proteins, as measured in a NanoString® assay. Data are represented as the mean of three replicates.



FIG. 7 is a set of western blot images that confirm overexpression of SF3B1 proteins in 293FT cells.



FIG. 8 is a graph depicting levels of aberrant splice variants in RNA isolated from 293FT cells expressing SF3B1WT or mutant SF3B1 proteins, as measured in a NanoString® assay.



FIG. 9A depicts a set of western blot images showing expression of SF3B1 alleles before and after shRNA-knockdown in Panc 05.04 cells. FIG. 9B depicts a graph showing levels of SF3B1 RNA detected by qPCR in Panc 05.04 cells before and after shRNA-knockdown of all SF3B1 alleles (“SF3B1PAN) or SF3B1WT or mutant SF3B1 (SF3B1MUT) alleles. qPCR data are represented as fold change relative to pLKO non-treated with doxycycline (mean±SD, n=3). Solid black, outlined, and gray bars indicate SF3B1PAN, SF3B1WT, and SF3B1MUT allele-specific qPCR data, respectively.



FIG. 10A depicts a set of western blot images showing expression of SF3B1 alleles before and after shRNA-knockdown in Panc 10.05 cells. FIG. 10B depicts a graph showing levels of SF3B1 RNA detected by qPCR in Panc 10.05 cells before and after shRNA-knockdown of SF3B1 alleles. qPCR data are represented as fold change relative to pLKO non-treated with doxycycline (mean±SD, n=3). Solid black, outlined, and gray bars indicate SF3B1PAN, SF3B1WT, and SF3B1MUT allele-specific qPCR data, respectively.



FIGS. 11A and 11B are a set of graphs depicting levels of splice variants in Panc 05.04 (FIG. 11A) and Panc 10.05 cells (FIG. 11B) before and after shRNA-knockdown of SF3B1 alleles, as measured in a NanoString® assay. Data are represented as mean of three biological replicates.



FIG. 12 is a set of graphs depicting growth curves of Panc 05.04 cells before (circles) and after (squares) shRNA-knockdown of SF3B1 alleles.



FIG. 13 is a set of graphs depicting growth curves of Panc 10.05 cells before (circles) and after (squares) shRNA-knockdown of SF3B1 alleles.



FIGS. 14A and 14B are a set of images of culture plates showing colony formation of Panc 05.04 cells (FIG. 14A) and Panc 10.05 (FIG. 14B) cells before and after shRNA-knockdown of SF3B1 alleles.



FIGS. 15A and 15B are a set of graphs showing the level of splicing of pre-mRNA Ad2 substrate in nuclear extracts from (FIG. 15A) 293F cells expressing Flag-tag SF3B1WT or SF3B1K700E (left and right panels [circles and triangles], respectively) and (FIG. 15B) Nalm-6 (SF3B1WT) and Nalm-6 SF3B1700E cells (left and right panels [circles and triangles], respectively) treated with varying concentrations of E7101. Data are represented as mean±SD, n=2.



FIG. 16A depicts a pair of graphs showing the binding of a radiolabeled E7107 analog to either SF3B1WT (circles, left panel) or SF3B1K700E (triangles, right panel) after incubation of the proteins with varying concentrations of E7107. FIG. 16B depicts upper panels, a pair of graphs showing the levels of EIF4A1 pre-mRNA (squares) and SLC25A19 mature RNA (inverted triangles) in Nalm-6 SF3B1K700K cells (left panel) and Nalm-6 SF3B1K700E cells (right panel) treated with varying concentrations of E7107, as measured by qPCR. FIG. 16B depicts lower panels, a pair of graphs showing the levels of abnormally spliced isoforms of abnormally spliced genes COASY (triangles) and ZDHHC16 (diamonds) in Nalm-6 SF3B1K700K cells (left panel) and Nalm-6 SF3B1K700E cells (right panel) treated with varying concentrations of E7107, as measured by qPCR. qPCR data in (FIG. 16B) are represented as mean±SD (n=3).



FIG. 17 is a set of graphs depicting levels of splice variants in Nalm-6 SF3B1K700K and Nalm-6 SF3B1K700E cells after treatment of cells with E7107 for two or six hours, as measured in a NanoString® assay. Data are expressed as fold change from DMSO-only treatment



FIG. 18 is a set of graphs depicting levels of splice variants in Nalm-6 SF3B1K700K and Nalm-6 SF3B1K700E cells after treatment of cells with E7107 for six hours, as measured by RNA-Seq analysis.



FIG. 19 is a set of graphs depicting levels of splice variants in Nalm-6 SF3B1K700K and Nalm-6 SF3B1K700E cells after treatment of cells with the numbered compounds indicated above the graphs, as measured by RNA-Seq analysis.



FIG. 20 is set of graphs depicting levels of splice variants in Nalm-6 SF3B1K700K and Nalm-6 SF3B1K700E cells at varying times following treatment of cells with E7107, as measured by qPCR of RNA. Data are represented as mean±SD (n=3). The upper panels of FIG. 20 depict the levels of EIF4A1 pre-mRNA (squares) and SLC25A19 mature RNA (inverted triangles) in Nalm-6 SF3B1K700K cells (left panel) and Nalm-6 SF3B1K700E cells (right panel) detected at certain times after treatment with E7107. The lower panels of FIG. 20 depict the levels of abnormally spliced isoforms of abnormally spliced genes COASY (triangles) and ZDHHC16 (diamonds) in Nalm-6 SF3B1K700K cells (left panel) and Nalm-6 SF3B1K700E cells (right panel) detected at certain times after treatment with E7107. Open circles show the concentration of E7107 (in μg/ml [right vertical axis]) as determined by mass spectrometry of tumor samples.



FIG. 21 is a set of graphs depicting levels of canonical and aberrant splice variants in Nalm-6 SF3B1K700K- and Nalm-6 SF3B1K700E-xenograft tumors (left and right sets of panels, respectively) at certain timepoints after treatment of xenograft mice with E7107, as measured in a NanoString® assay. Data are represented as mean of three replicates.



FIG. 22 is a set of graphs depicting levels of canonical and aberrant splice variants in Panc 05.04-xenograft tumors at certain timepoints after treatment of xenograft mice with E7107 at various concentrations, as measured in a NanoString® assay (n=4 mice for each group).



FIG. 23 is a graph depicting tumor volume (shown as mean±SEM) in Nalm-6 SF3B1K700E-xenograft mice following treatment with E7107, with control mice treated with vehicle shown by open circles (n=10 animals for each group). For E7107-treated animals, inverted triangles=1.25 mg/kg, triangles=2.5 mg/kg, and squares=5 mg/kg.



FIG. 24 is a graph depicting survival rates in 10-animal cohorts of Nalm-6 SF3B1K700E-xenograft mice following treatment with E7107, with an untreated cohort shown by the solid black line. For E7107-treated animals, dashed line=1.25 mg/kg, gray line=2.5 mg/kg, and dotted line=5 mg/kg.



FIG. 25 is set of graphs depicting levels of splice variants in SF3B1WT and neomorphic SF3B1 mutant CLL cell samples following treatment with 10 nM E7107 for 6 hours, as measured by analysis. Data are represented as mean values (n=3).





DESCRIPTION OF THE EMBODIMENTS

In certain aspects, the methods of the invention provide assays for measuring the amount of a splice variant in a cell, thereby determining whether a patient has a cancer with a neomorphic SF3B1 mutation. In some embodiments, at least one of the measured splice variants is an aberrant splice variant associated with a neomorphic mutation in an SF3B1 protein. In additional aspects, the measurement of a splice variant in a cell may be used to evaluate the ability of a compound to modulate a mutant neomorphic SF3B1 protein in a cell.


To assist in understanding the present invention, certain terms are first defined. Additional definitions are provided throughout the application.


As used herein, the term “mutant SF3B1 protein” includes SF3B1 proteins that differ in amino acid sequence from the human wild type SF3B1 protein set forth in SEQ ID NO:1200 (GenBank Accession Number NP_036565, Version NP_036565.2) (S. Bonnal, L. Vigevani, and J. Valcarcel, “The spliceosome as a target of novel antitumour drugs,” Nat. Rev. Drug Discov. 11:847-59 [2012]). Certain mutant SF3B1 proteins are “neomorphic” mutants, which refers to mutant SF3B1 proteins that are associated with differential expression of aberrant splice variants. In certain embodiments, neomorphic SF3B1 mutants include K700E, K666N, R625C, G742D, R625H, E622D, H662Q, K666T, K666E, K666R, G740E, Y623C, T663I, K741N, N626Y, T663P, H662R, G740V, D781E, or R625L. In other embodiments, neomophic SF3B1 mutants include E622D, E622K, E622Q, E622V, Y623C, Y623H, Y623S, R625C, R625G, R625H, R625L, R625P, R625S, N626D, N626H, N626I, N626S, N626Y, H662D, H662L, H662Q, H662R, H662Y, T663I, T663P, K666E, K666M, K666N, K666Q, K666R, K666S, K666T, K700E, V701A, V701F, V701I, I704F, I704N, I704S, I704V, G740E, G740K, G740R, G740V, K741N, K741Q, K741T, G742D, D781E, D781G, or D781N. Certain SF3B1 mutations are not associated with expression of aberrant splice variants, including K700R.


The term “splice variant” as used herein includes nucleic acid sequences that span a junction either between two exon sequences or across an intron-exon boundary in a gene, where the junction can be alternatively spliced. Alternative splicing includes alternate 3′ splice site selection (“3′ss”), alternate 5′ splice site selection (“5′ss”), differential exon inclusion, exon skipping, and intron retention (FIG. 1). Certain splice variants associated with a given genomic location may be referred to as wild type, or “canonical,” variants. These splice variants are most abundantly expressed in cells that do not contain a neomorphic SF3B1 mutant protein. Additional splice variants may be referred to as “aberrant” splice variants, which differ from the canonical splice variant and are primarily associated with the presence of a neomorphic SF3B1 mutant protein in a cell. Aberrant splice variants may alternatively be referred to as “abnormal” or “noncanonical” splice variants. In certain circumstances, cells with a wild type or non-neomorphic SF3B1 protein have low or undetected amounts of an aberrant splice variant, while cells with a neomorphic SF3B1 protein have levels of an aberrant splice variant that are elevated relative to the low or undetected levels in the wild type SF3B1 cells. In some cases, an aberrant splice variant is a splice variant that is present in a wild type SF3B1 cell but is differentially expressed in a cell that has a neomorphic SF3B1 mutant, whereby the latter cell has a level of the aberrant splice variant that is elevated or reduced relative to the level in the wild type SF3B1 cell. Different types of cells containing a neomorphic SF3B1 mutant, such as different types of cancer cells, may have differing levels of expression of certain aberrant splice variants. In addition, certain aberrant splice variants present in one type of cell containing a neomorphic SF3B1 mutant may not be present in other types of cells containing a neomorphic SF3B1 mutant. In some cases, patients with a neomorphic SF3B1 mutant protein may not express an aberrant splice variant or may express an aberrant splice variant at lower levels, due to low allelic frequency of the neomorphic SF3B1 allele. The identity and relative expression levels of aberrant splice variants associated with various types of cells containing neomorphic SF3B1 mutants, such as certain cancer cells, will be apparent from the description and examples provided herein.


The term “evaluating” includes determining the ability of a compound to treat a disease associated with a neomorphic SF3B1 mutation. In some instances, “evaluating” includes determining whether or to what degree a compound modulates aberrant splicing events associated with a neomorphic SF3B1 protein. Modulation of the activity of an SF3B1 protein may encompass up-regulation or down-regulation of aberrant splice variant expression associated with a neomorphic SF3B1 protein. Additionally, “evaluating” includes distinguishing patients that may be successfully treated with a compound that modulates the expression of splice variants associated with a neomorphic SF3B1 protein.


The use of the word “a”, “an” or “the” when used in conjunction with the term “comprising” in the claims or the specification may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.” “Or” is to be read inclusively to mean “and/or” unless explicitly indicated to refer to alternatives only, such as where alternatives are mutually exclusive.


Splice Variants


Splice variants of the invention are listed in Table 1. Table 1 provides the genomic location of each canonical (“WT”) and aberrant (“Ab.”) splice junction, as well as the sequence. Each sequence listed in the table contains 20 nucleotides from each of the 3′ and 5′ sides of a splice junction (i.e., the splice junction is at the midpoint of the listed nucleotide sequence). The “Avg WT %” and “Avg Ab. %” columns provide the average percentage count that the canonical (WT) or aberrant splice variant, respectively, represented out of the total counts of all splice variants that utilize a shared splice site, where the counts were determined as set forth in Example 1. The “Log2 Fold Change” column provides the log2 of the fold change observed between percentage counts of canonical and aberrant cohorts (see Example 1). The “FDR Q-Value” column provides, as a measure of statistical significance, q-values calculated using the Benjamini-Hochberg procedure from p-values, which in turn were determined using the moderated t-test defined in the Bioconductor's limma package (available at http://www.bioconductor.org) (see Example 1). The “Event” column indicates the nature of the aberrant splice variant, where “3′ss” indicates alternate 3′ splice site selection, “5′ss” indicates alternate 5′ splice site selection, “exon incl.” indicates differential exon inclusion, and “exon skip” indicates exon skipping. The “Type” column refers to the cancer type of the sample in which the aberrant splice variant was identified, where “Br.” indicates breast cancer, “CLL” indicates chronic lymphocytic leukemia, and “Mel.” indicates melanoma.



















TABLE 1








Aberrant

Avg
Avg
Log2






Aberrant

sequence (SEQ
WT sequence
WT
Ab.
Fold
FDR Q-



junction
WT junction
ID NO)
(SEQ ID NO)
%
%
Diff.
Value
Event
Type

























1
chr2:
chr2:
AGCAAGTAGAAG
AGCAAGTAGAAG
0
56
5.83
6.30E−07
3′ss
Br.



109102364-109102954
109102364-109102966
TCTATAAAATTT
TCTATAAAATAC





ACCCCCAGATAC
AGCTGGCTGAAA





AGCT (1)
TAAC (2)





2
chr16:
chr16:
CGGGCCGCATCA
CGGGCCGCATCA
0
51
5.70
2.38E−07
3′ss
Br.



708344-708509
708344-708524
TCCGGGAGAGCA
TCCGGGAGCTGC





CTGTGTTCCAGC
CCGGTGTCCACC





TGCC (3)
CTGA (4)





3
chr3:
chr3:
CTGGAGCCGGCG
CTGGAGCCGGCG
0
51
5.70
2.19E−07
3′ss
Br.



50380021-50380348
50380000-50380348
GGAAGGAGTGTG
GGAAGGAGGCAA





CTGGTTCCTCTC
GCTGCAGCAGTT





CCCA (5)
CGAG (6)





4
chr19:
chr19:
GGCCCTTTTGTC
GGCCCTTTTGTC
0
48
5.61
2.32E−06
3′ss
Br.



57908542-57909780
57908542-57909797
CTCACTAGCATT
CTCACTAGGTTC





TCTGTTCTGACA
TTGGCATGGAGC





GGTT (7)
TGAG (8)





5
chr2:
chr2:
TGGGAGGAGCAT
TGGGAGGAGCAT
0
47
5.58
7.79E−07
3′ss
Br.



97285513-97297048
97285499-97297048
GTCAACAGAGTT
GTCAACAGGACT





TCCCTTATAGGA
GGCTGGACAATG





CTGG (9)
GCCC (10)





6
chr19:
chr19:
GATGGTGGATGA
GATGGTGGATGA
0
46
5.55
1.10E−05
3′ss
Br.



23545541-23556543
23545527-23556543
ACCCACAGTTTT
ACCCACAGGTAT





TTTTTTTCAGGT
ATGTCCTCATTT





ATAT (11)
TCCT (12)





7
chr10:
chr10:
TACCTCTGGTTC
TACCTCTGGTTC
0
46
5.55
3.63E−09
3′ss
Br.



99214556-99215395
99214556-99215416
CTGTGCAGTCTT
CTGTGCAGTTCT





CGCCCCTCTTTT
GTGGCACTTGCC





CTTA (13)
CTGG (14)





8
chr18:
chr18:
TTGGACCGGAAA
TTGGACCGGAAA
0
44
5.49
4.30E−09
3′ss
Br.



683395-685920
683380-685920
AGACTTTGAGTC
AGACTTTGATGA





TCTTTTTGCAGA
TGGATGCCAACC





TGAT (15)
AGCG (16)





9
chr17:
chr17:
ACCCAAGCCTTG
ACCCAAGCCTTG
0
44
5.49
1.50E−07
exon
Br.



40714237-40714373
40714237-40714629
AGGTTTCATTTC
AGGTTTCAGCCT




incl.





CCCCTCCCAGGA
GGGCAGCATGGC





TTTC (17)
CGTA (18)





10
chr5:
chr5:
AGCATTGCTAGA
AGCATTGCTAGA
0
41
5.39
4.86E−09
3′ss
Br.



139815842-139818078
139815842-139818045
AGCAGCAGCTTT
AGCAGCAGGAAT





TGCAGATCCTGA
TGGCAAATTGTC





GGTA (19)
AACT (20)





11
chr1:
chr1:
CAAGTATATGAC
CAAGTATATGAC
0
39
5.32
1.31E−10
3′ss
Br.



245246990-245288006
245246990-245250546
TGAAGAAGATCC
TGAAGAAGGTGA





TGAATTCCAGCA
GCCTTTTTCTCA





AAAC (21)
AGAG (22)





12
chr3:
chr3:
TGCAGTTTGGTC
TGCAGTTTGGTC
0
36
5.21
9.63E−09
3′ss
Br.



9960293-9962150
9960293-9962174
AGTCTGTGCCTT
AGTCTGTGGGCT





CCTCACCCCTCT
CTGTGGTATATG





CCTC (23)
ACTG (24)





13
chr1:
chr1:
TCTTTGGAAAAT
TCTTTGGAAAAT
0
29
4.91
3.27E−07
3′ss
Br.



101458310-101460665
101458296-101460665
CTAATCAATTTT
CTAATCAAGGGA





CTGCCTATAGGG
AGGAAGATCTAT





GAAG (25)
GAAC (26)





14
chr7:
chr7:
GTATCAAAGTGT
GTATCAAAGTGT
0
28
4.86
5.02E−05
3′ss
Br.



94157562-94162500
94157562-94162516
GGACTGAGATTT
GGACTGAGGATT





GTCTTCCTTTAG
CCATTGCAAAGC





GATT (27)
CACA (28)





15
chr20:
chr20:
AGAACTGCACCT
AGAACTGCACCT
0
27
4.81
1.50E−07
3′ss
Br.



62701988-62703210
62701988-62703222
ACACACAGCCCT
ACACACAGGTGC





GTTCACAGGTGC
AGACCCGCAGCT





AGAC (29)
CTGA (30)





16
chr17:
chr17:
GGAGCAGTGCAG
GGAGCAGTGCAG
0
25
4.70
9.63E−06
3′ss
Br.



71198039-71199162
71198039-71199138
TTGTGAAATCAT
TTGTGAAAGTTT





TACTTCTAGATG
TGATTCATGGAT





ATGC (31)
TCAC (32)





17
chr17:
chr17:
CTATTTCACTCT
CTATTTCACTCT
0
25
4.70
5.99E−08
3′ss
Br.



7131030-7131295
7131102-7131295
CCCCCGAACCTA
CCCCCGAAATGA





TCCAGGTTCCTC
GCCCATCCAGCC





CTCC (33)
AATT (34)





18
chr20:
chr20:
TTTGCAGGGAAT
TTTGCAGGGAAT
0
25
4.70
2.72E−07
3′ss
Br.



35282126-35284762
35282104-35284762
GGGCTACATCCC
GGGCTACATACC





CTTGGTTCTCTG
ATCTGCCAGCAT





TTAC (35)
GACT (36)





19
chr2:
chr2:
TGACCACGGAGT
TGACCACGGAGT
0
25
4.70
1.61E−06
3′ss
Br.



232196609-232209660
232196609-232209686
ACCTGGGGCCCT
ACCTGGGGATCA





TTTTTCTCTTTC
TGACCAACACGG





CTTC (37)
GGAA (38)





20
chr17:
chr17:
AGACCTACCAGA
AGACCTACCAGA
0
24
4.64
7.16E−06
3′ss
Br.



62574712-62576906
62574694-62576906
AGGCTATGTGTT
AGGCTATGAACA





TATTAATTTTAC
GAGGACAACGCA





AGAA (39)
ACAA (40)





21
chr12:
chr12:
ATTTGGACTCGC
ATTTGGACTCGC
0
23
4.58
8.14E−08
3′ss
Br.



105601825-105601935
105601807-105601935
TAGCAATGATGT
TAGCAATGAGCA





CTGTTTATTTTT
TGACCTCTCAAT





AGAG (41)
GGCA (42)





22
chr12:
chr12:
CATGTGGAATCC
CATGTGGAATCC
0
22
4.52
1.87E−04
3′ss
Br.



53836517-53837270
53836517-53837174
CAATGCCGGCCC
CAATGCCGGGCA





CTGTCCTCCTCC
GCCAGGGCCAAA





CCCA (43)
TCCA (44)





23
chr22:
chr22:
CTGGGAGGTGGC
CTGGGAGGTGGC
0
22
4.52
2.76E−08
3′ss
Br.



19044699-19050714
19044675-19050714
ATTCAAAGCCCC
ATTCAAAGGCTC





ACCTTTTGTCTC
TTCAGAGGTGTT





CCCA (45)
CCTG (46)





24
chr11:
chr11:
GGATGACCGGGA
GGATGACCGGGA
0
21
4.46
4.61E−08
3′ss
Br.



71939542-71939690
71939542-71939770
TGCCTCAGTCAC
TGCCTCAGATGG





TTTACAGCTGCA
GGAGGATGAGAA





TCGT (47)
GCCC (48)





25
chr20:
chr20:
ACATGAAGGTGG
ACATGAAGGTGG
0
21
4.46
2.63E−08
3′ss
Br.



34144042-34144725
34144042-34144743
ACGGAGAGGCTC
ACGGAGAGGTAC





CCCTCCCACCCC
TGAGGACAAATC





AGGT (49)
AGTT (50)





26
chr6:
chr6:
AGAGAAGTCGTT
AGAGAAGTCGTT
2
64
4.44
2.91E−10
3′ss
Br.



31919381-31919565
31919381-31919651
TCATTCAAGTCA
TCATTCAAGTTG





GCTAAGACACAA
GTGTAATCAGCT





GCAG (51)
GGGG (52)





27
chr1:
chr1:
TCACTCAAACAG
TCACTCAAACAG
0
20
4.39
9.99E−07
3′ss
Br.



179835004-179846373
179834989-179846373
TAAACGAGTTTT
TAAACGAGGTAT





ATCATTTACAGG
GTGACGCATTCC





TATG (53)
CAGA (54)





28
chr1:
chr1:
CGATCTCCCAAA
CGATCTCCCAAA
0
20
4.39
1.35E−09
3′ss
Br.



52880319-52880412
52880319-52880433
AGGAGAAGTCTG
AGGAGAAGCCCC





ACCAGTCTTTTC
TCCCCTCGCCGA





TACA (55)
GAAA (56)





29
chr8:
chr8:
TTATTTTACACA
TTATTTTACACA
0
20
4.39
1.49E−09
3′ss
Br.



38095145-38095624
38095145-38095606
ATCCAAAGCCAG
ATCCAAAGCTTA





TTGCAGGGTCTG
TGGTGCATTACC





ATGA (57)
AGCC (58)





30
chr19:
chr19:
TGCCTGTGGACA
TGCCTGTGGACA
0
19
4.32
2.37E−05
3′ss
Br.



14031735-14034130
14031735-14034145
TCACCAAGCCTC
TCACCAAGGTGC





GTCCTCCCCAGG
CGCCTGCCCCTG





TGCC (59)
TCAA (60)





31
chr14:
chr14:
AGTTAGAATCCA
AGTTAGAATCCA
0
18
4.25
1.65E−10
3′ss
Br.



74358911-74360478
74358911-74360499
AACCAGAGTGTT
AACCAGAGCTCC





GTCTTTTCTCCC
TGGTACAGTTTG





CCCA (61)
TTCA (62)





32
chr19:
chr19:
ATATGCTGGAAT
ATATGCTGGAAT
0
18
4.25
8.07E−08
3′ss
Br.



45314603-45315482
45314603-45315419
GGTTCCTTGTCA
GGTTCCTTACCG





CAATGCACGACA
ACCGCTCGGGAG





CCCG (63)
CTCG (64)





33
chr1:
chr1:
ATCAGAAATTCG
ATCAGAAATTCG
0
18
4.25
4.25E−08
3′ss
Br.



212515622-212519131
212515622-212519144
TACAACAGGTTT
TACAACAGCTCC





CTTTTAAAGCTC
TGGAGCTTTTTG





CTGG (65)
ATAG (66)





34
chr9:
chr9:
AAATGAAGAAAC
AAATGAAGAAAC
0
18
4.25
1.31E−10
3′ss
Br.



125759640-125760854
125759640-125760875
TCCTAAAGCCTC
TCCTAAAGATAA





TCTCTTTCTTTG
AGTCCTGTTTAT





TTTA (67)
GACC (68)





35
chr11:
chr11:
CATAAAATTCTA
CATAAAATTCTA
0
17
4.17
1.35E−06
3′ss
Br.



4104212-4104471
4104212-4104492
ACAGCTAATTCT
ACAGCTAAGCAA





CTTTCCTCTGTC
GCACTGAGCGAG





TTCA (69)
GTGA (70)





36
chr12:
chr12:
GCCTGCCTTTGA
GCCTGCCTTTGA
0
17
4.17
3.58E−07
3′ss
Br.



113346629-113348840
113346629-113348855
TGCCCTGGATTT
TGCCCTGGGTCA





TGCCCGAACAGG
GTTGACTGGCGG





TCAG (71)
CTAT (72)





37
chr17:
chr17:
CCAAGCTGGTGT
CCAAGCTGGTGT
0
17
4.17
4.19E−04
3′ss
Br.



78188582-78188831
78188564-78188831
GCGCACAGGCCT
GCGCACAGGCAT





CTCTTCCCGCCC
CATCGGGAAGAA





AGGC (73)
GCAC (74)





38
chr20:
chr20:
CTCCTTTGGGTT
CTCCTTTGGGTT
0
17
4.17
2.67E−07
3′ss
Br.



45354963-45355453
45354963-45355502
TGGGCCAGGCCC
TGGGCCAGTGAC





CAGGTCCCACCA
CTGGCTTGTCCT





CAGC (75)
CAGC (76)





39
chr12:
chr12:
AATATTGCTTTA
AATATTGCTTTA
0
16
4.09
2.79E−07
3′ss
Br.



116413154-116413319
116413118-116413319
CCAAACAGGGAC
CCAAACAGGTCA





CCCTTCCCCTTC
CGGAGGAGTAAA





CCCA (77)
GTAT (78)





40
chr14:
chr14:
CAGTTATAAACT
CAGTTATAAACT
0
16
4.09
4.46E−07
3′ss
Br.



71059726-71060012
71059705-71060012
CTAGAGTGAGTT
CTAGAGTGCTTA





TATTTTCCTTTT
CTGCAGTGCATG





ACAA (79)
GTAT (80)





41
chr16:
chr16:
GCCTGCCCCGGA
GCCTGCCCCGGA
0
15
4.00
7.77E−06
3′ss
Br.



30012851-30016688
30012851-30016541
AACTCAAGATGT
AACTCAAGATGG





TCAGCGATGCAG
CGGTGGGACCCC





GTAG (81)
CCGA (82)





42
chr17:
chr17:
TTCAGGAGGTGG
TTCAGGAGGTGG
0
15
4.00
3.26E−05
3′ss
Br.



57148329-57153007
57148308-57153007
AGCACCAGATAA
AGCACCAGTTGC





TTTTTTTCCTCA
GGTCTTGTAGTA





CACA (83)
AGAG (84)





43
chr16:
chr16:
GGATCCTTCACC
GGATCCTTCACC
0
14
3.91
3.01E−07
3′ss
Br.



1402307-1411686
1402307-1411743
CGTGTCTGTCTT
CGTGTCTGGACC





TGCAGACAGGTT
CGTGCATCTCTT





CTGT (85)
CCGA (86)





44
chr3:
chr3:
ATTTGGATCCTG
ATTTGGATCCTG
0
14
3.91
8.71E−07
3′ss
Br.



196792335-196792578
196792319-196792578
TGTTCCTCTTTT
TGTTCCTCATAC





TTTCTGTTAAAG
AACTAGACCAAA





ATAC (87)
ACGA (88)





45
chr14:
chr14:
AGATGTCAGGTG
AGATGTCAGGTG
0
13
3.81
1.55E−05
3′ss
Br.



75356052-75356580
75356052-75356599
GGAGAAAGCCTT
GGAGAAAGCTGT





TGATTGTCTTTT
TGGAGACACAGT





CAGC (89)
TGCA (90)





46
chr18:
chr18:
AGAAAGAGCATA
AGAAAGAGCATA
0
13
3.81
9.84E−07
3′ss
Br.



33605641-33606862
33573263-33606862
AATTGGAAATAT
AATTGGAAGAGT





TGGACATGGGCG
ACAAGCGCAAGC





TATC (91)
TAGC (92)





47
chr1:
chr1:
TCAGCCCTCTGA
TCAGCCCTCTGA
0
13
3.81
6.10E−07
3′ss
Br.



226036315-226036597
226036255-226036597
ACTACAAAGGTG
ACTACAAAACAG





TTTGTTCACAGA
AAGAGCCTGCAA





GATC (93)
GTGA (94)





48
chr6:
chr6:
CCGGGGCCTTCG
CCGGGGCCTTCG
3
51
3.70
1.35E−09
3′ss
Br.



10723474-10724788
10723474-10724802
TGAGACCGCTTG
TGAGACCGGTGC





TTTTCTGCAGGT
AGGCCTGGGGTA





GCAG (95)
GTCT (96)





49
chr2:
chr2:
CAAGTCCATCTC
CAAGTCCATCTC
0
12
3.70
5.71E−03
3′ss
Br.



132288400-132289210
132288400-132289236
TAATTCAGGGTC
TAATTCAGGCAA





TGACTTGCAGCC
GGCCAGGCCCCA





AACT (97)
GCCC (98)





50
chr2:
chr2:
CAAGATAGATAT
CAAGATAGATAT
0
12
3.70
4.26E−06
3′ss
Br.



170669034-170671986
170669016-170671986
TATAGCAGGTGG
TATAGCAGAACT





CTTTTGTTTTAC
TCGATATGACCT





AGAA (99)
GCCA (100)





51
chr15:
chr15:
GAAACCAACTAA
GAAACCAACTAA
1
24
3.64
4.30E−09
3′ss
Br.



59209219-59224554
59209198-59224554
AGGCAAAGCCCA
AGGCAAAGGTAA





TTTTCCTTCTTT
AAAACATGAAGC





CGCA (101)
AGAT (102)





52
chr11:
chr11:
GGGGACAGTGAA
GGGGACAGTGAA
0
11
3.58
5.99E−08
3′ss
Br.



57100545-57100908
57100623-57100908
ATTTGGTGGCAA
ATTTGGTGGGCA





GAATGAGGTGAC
GCTGCTTTCCTT





ACTG (103)
TGAC (104)





53
chr1:
chr1:
CTCAGAGCCAGG
CTCAGAGCCAGG
0
11
3.58
3.15E−07
3′ss
Br.



35871069-35873587
35871069-35873608
CTGTAGAGATGT
CTGTAGAGTCCG





TTTCTACCTTTC
CTCTATCAAGCT





CACA (105)
GAAG (106)





54
chr2:
chr2:
GAGGAGCCACAC
GAGGAGCCACAC
0
11
3.58
2.22E−07
3′ss
Br.



220044485-220044888
220044485-220044831
TCTGACAGATAC
TCTGACAGTGAG





CTGGCTGAGAGC
GGTGCGGGGTCA





TGGC (107)
GGCG (108)





55
chr5:
chr5:
ACTCGCGCCTCT
ACTCGCGCCTCT
0
11
3.58
7.04E−07
3′ss
Br.



150411955-150413168
150411944-150413168
TCCATCTGTTTT
TCCATCTGCCGG





GTCGCAGCCGGA
AATACACCTGGC





ATAC (109)
GTCT (110)





56
chrX:
chrX:
ACTTCCTTAGTG
ACTTCCTTAGTG
0
11
3.58
7.37E−07
3′ss
Br.



47059013-47059808
47059013-47060292
GTTTCCAGGTTG
GTTTCCAGGTGG





CCAGGGCACTGC
TGGTGCTCACCA





AGCT (111)
ACAC (112)





57
chrX:
chrX:
GTCTTGAGAATT
ACTTCCTTAGTG
0
11
3.58
6.70E−06
5′ss
Br.



47059943-47060292
47059013-47060292
GGAAGCAGGTGG
GTTTCCAGGTGG





TGGTGCTCACCA
TGGTGCTCACCA





ACAC (113)
ACAC (112)





58
chr20:
chr20:
TCCAGAGCCCAC
TCCAGAGCCCAC
2
34
3.54
4.87E−09
3′ss
Br.



330007-330259
330007-330281
AGTCCCAGCTGC
AGTCCCAGGGGT





ACCTTACCTGCT
CCATGATGCCGA





CCCC (114)
GCTG (115)





59
chr18:
chr18:
CCAAGTTTTGTG
CCAAGTTTTGTG
1
22
3.52
1.96E−05
3′ss
Br.



224200-224923
224179-224923
AAAGAAAGTGTA
AAAGAAAGAACA





TGTTTTGTTCAC
TCAGATACCAAA





GACA (116)
CCTA (117)





60
chr11:
chr11:
TCTTCACAGAAC
TCTTCACAGAAC
0
10
3.46
2.99E−08
3′ss
Br.



47195466-47196565
47195391-47196565
ACACTCAAGTGC
ACACTCAACCCC





TTGTAGGTCTTG
CTGCCTGGGATG





GTGC (118)
CGCC (119)





61
chr12:
chr12:
GAGAAGCTCACG
TCTTGGAGGAGC
0
10
3.46
4.11E−02
exon
Br.



56604352-56606779
56604352-56607741
ATTACCAGGCAC
CAGTACAGGCAC




incl.





CTCATTGTGAAC
CTCATTGTGAAC





ATGC (120)
ATGC (121)





62
chr14:
chr14:
GTGGGGGGCCAT
GTGGGGGGCCAT
0
10
3.46
3.25E−08
3′ss
Br.



23237380-23238985
23237380-23238999
TGCTGCATTTTG
TGCTGCATGTAC





TATTTTCCAGGT
AGTCTTTGCCCG





ACAG (122)
CTGC (123)





63
chr17:
chr17:
TACTGAAATGTG
TACTGAAATGTG
0
10
3.46
2.49E−05
3′ss
Br.



34942628-34943454
34942628-34943426
ATGAACATATCC
ATGAACATATCC





AGGTAATCGAGA
AGAAGCTTGGAA





GACC (124)
GCTG (125)





64
chr1:
chr1:
GAATCTCTTATC
GAATCTCTTATC
0
10
3.46
2.93E−06
3′ss
Br.



145581564-145583935
145581564-145583914
ATTGATGGTTCC
ATTGATGGTTTA





TGTTCAGATTGT
TTTATGGAGATT





GATG (126)
CTTA (127)





65
chr5:
chr5:
CTCCATGCTCAG
CTCCATGCTCAG
1
20
3.39
6.76E−06
3′ss
Br.



869519-870587
865696-870587
CTCTCTGGTTTC
CTCTCTGGGGAA





TTTCAGGGCCTG
GGTGAAGAAGGA





CCAT (128)
GCTG (129)





66
chr12:
chr12:
CTTGGAGCTGAC
CTTGGAGCTGAC
7
79
3.32
1.30E−08
3′ss
Br.



107378993-107380746
107379003-107380746
GCCGACGGGGAA
GCCGACGGTTTA





CTGACAAGATCA
TTGCAGGGAACT





CATT (130)
GACA (131)





67
chr7:
chr7:
TCCAGCCTGGGC
CTATCAAAAGAG
1
19
3.32
4.35E−08
exon
Br.



8261028-8267267
8261028-8268230
GACAGAAGTCTT
GATATGTTTCTT




incl.





GTCTCAAGAAGA
GTCTCAAGAAGA





AAAC (132)
AAAC (133)





68
chr10:
chr10:
TGCGGAGCAAGA
TGCGGAGCAAGA
0
9
3.32
1.37E−04
3′ss
Br.



5497081-5498027
5497081-5498049
GTGGACATCGTT
GTGGACATAAAC





TGTTTCCCATTT
TTTACATTTTCC





CTCC (134)
TGTT (135)





69
chr11:
chr11:
AGTCCAGCCCCA
AGTCCAGCCCCA
0
9
3.32
4.66E−07
3′ss
Br.



64900740-64900940
64900723-64900940
GCATGGCACCTC
GCATGGCAGTCC





TCCCCACTCCTA
TGTACATCCAGG





GGTC (136)
CCTT (137)





70
chr19:
chr19:
CAAGCAGGTCCA
CAAGCAGGTCCA
0
9
3.32
1.49E−09
3′ss
Br.



5595521-5598803
5595508-5598803
AAGAGAGATTTT
AAGAGAGAAGCT





GGTAAACAGAGC
CCAAGAGTCAGG





TCCA (138)
ATCG (139)





71
chr22:
chr22:
CTCTCTCCAACC
CTCTCTCCAACC
0
9
3.32
8.58E−06
3′ss
Br.



39064137-39066874
39064137-39066888
TGCATTCTCATC
TGCATTCTTTGG





TCGCCCACAGTT
ATCGATCAACCC





GGAT (140)
GGGA (141)





72
chr9:
chr9:
CACCACGCCGAG
CACCACGCCGAG
2
28
3.27
2.13E−08
3′ss
Br.



125023777-125026993
125023787-125026993
GCCACGAGACAT
GCCACGAGTATT





TGATGGAAGCAG
TCATAGACATTG





AAAC (142)
ATGG (143)





73
chr15:
chr15:
GCCTCACTGAGC
GCCTCACTGAGC
1
18
3.25
5.94E−09
exon
Br.



25207356-25212175
25207356-25213078
AACCAAGAGTAG
AACCAAGAGTGT




incl.





TGACTTGTCAGG
CAGTTGTACCCG





AGGA (144)
AGGC (145)





74
chr9:
chr9:
GGGAGATGGATA
GGGAGATGGATA
3
35
3.17
6.19E−08
3′ss
Br.



35813153-35813262
35813142-35813262
CCGACTTGCTCA
CCGACTTGTGAT





ATTTCAGTGATC
CAACGATGGGAA





AACG (146)
GCTG (147)





75
chr6:
chr6:
AGGATGTGGCTG
AGGATGTGGCTG
1
17
3.17
5.18E−06
3′ss
Br.



31602334-31602574
31602334-31602529
GCACAGAAGTGT
GCACAGAAATGA





CATCAGGTCCCT
GTCAGTCTGACA





GCAG (148)
GTGG (149)





76
chr11:
chr11:
TTCTCCAGGACC
TTCTCCAGGACC
0
8
3.17
6.00E−04
3′ss
Br.



125442465-125445146
125442465-125445158
TTGCCAGACCTT
TTGCCAGAGGAA





TTCTATAGGGAA
TCAAAGACTCCA





TCAA (150)
TCTG (151)





77
chr13:
chr13:
AGCTGAAATTTC
AGCTGAAATTTC
0
8
3.17
1.20E−06
3′ss
Br.



113915073-113917776
113915073-113917800
CAGTAAAGGGGG
CAGTAAAGCCTG





GTTTTATTCTTC
GAGATTTGAAAA





TTTT (152)
AGAG (153)





78
chr16:
chr16:
GATGTCACTGTG
GATGTCACTGTG
0
8
3.17
4.76E−02
3′ss
Br.



14966186-14968874
14966186-14968892
ACTATCAAGGGC
ACTATCAAGTCT





CGTCTTTCTTCT
TCCATCGACAGT





AGGT (154)
GAAC (155)





79
chr2:
chr2:
TATCCATTCCTG
TATCCATTCCTG
0
8
3.17
2.22E−07
3′ss
Br.



178096758-178097119
178096736-178097119
AGTTACAGTATA
AGTTACAGTGTC





AACTTCCTTCTC
TTAATATTGAAA





ATGC (156)
ATGA (157)





80
chrX:
chrX:
TACAAGAGCTGG
TACAAGAGCTGG
0
8
3.17
2.14E−05
3′ss
Br.



153699660-153699819
153699660-153699830
GTGGAGAGGGTC
GTGGAGAGGTAT





CCAACAGGTATT
TATCGAGACATT





ATCG (158)
GCAA (159)





81
chr19:
chr19:
AGCCATTTATTT
AGCCATTTATTT
3
31
3.00
7.42E−06
3′ss
Br.



9728842-9730107
9728855-9730107
GTCCCGTGGGAA
GTCCCGTGGGTT





CCAATCTGCCCT
TTTTTCCAGGGA





TTTG (160)
ACCA (161)





82
chr1:
chr1:
AGTTACAACGAA
AGTTACAACGAA
2
23
3.00
8.51E−06
3′ss
Br.



185056772-185060696
185056772-185060710
CACCTCAGTGAC
CACCTCAGGAGG





TCTTTTACAGGA
CAATAACAGATG





GGCA (162)
GCTT (163)





83
chr15:
chr15:
TCACACAGGATA
GCCTCACTGAGC
1
15
3.00
3.25E−08
exon
Br.



25212299-25213078
25207356-25213078
ATTTGAAAGTGT
AACCAAGAGTGT




incl.





CAGTTGTACCCG
CAGTTGTACCCG





AGGC (164)
AGGC (145)





84
chr11:
chr11:
CGGCGCGGGCAA
CGGCGCGGGCAA
0
7
3.00
1.28E−08
3′ss
Br.



62648919-62649352
62648919-62649364
CCTGGCGGCCCC
CCTGGCGGGTCT





CATTTCAGGTCT
GAAGGGGCGTCT





GAAG (165)
CGAT (166)





85
chr11:
chr11:
CCACCGCCATCG
CCACCGCCATCG
0
7
3.00
4.87E−09
3′ss
Br.



64877395-64877934
64877395-64877953
ACGTGCAGTACC
ACGTGCAGGTGG





TCTTTTTACCAC
GGCTCCTGTACG





CAGG (167)
AAGA (168)





86
chr19:
chr19:
CTATGGGCTCAC
CTATGGGCTCAC
0
7
3.00
1.24E−03
3′ss
Br.



41084118-41084353
41084118-41084367
TCCTCTGGTCCT
TCCTCTGGTTCG





CCTGTTGCAGTT
TCGCCTGCAGCT





CGTC (169)
TCGA (170)





87
chr1:
chr1:
TATCTCTGGGAA
TATCTCTGGGAA
0
7
3.00
3.66E−06
3′ss
Br.



35917392-35919157
35917377-35919157
AAAACACATTTC
AAAACACAGGGA





TTTTTTTGCAGG
CCTGATGGGGTG





GGAC (171)
CAGC (172)





88
chr22:
chr22:
TCATCCAGAGCC
TCATCCAGAGCC
0
7
3.00
1.95E−06
3′ss
Br.



50966161-50966940
50966146-50966940
CAGAGCAGGGGA
CAGAGCAGATGC





TGTCTGACCAGA
AAGTGCTGCTGG





TGCA (173)
ACCA (174)





89
chr9:
chr9:
CCAAGGACTGCA
CCAAGGACTGCA
0
7
3.00
8.14E−08
3′ss
Br.



139837449-139837800
139837395-139837800
CTGTGAAGGCCC
CTGTGAAGATCT





CCGCCCCGCGAC
GGAGCAACGACC





CTGG (175)
TGAC (176)





90
chr1:
chr1:
CCCGAGCTCAGA
CCCGAGCTCAGA
4
38
2.96
2.79E−08
3′ss
Br.



3548881-3549961
3548902-3549961
GAGTAAATTCTC
GAGTAAATATGA





CTTACAGACACT
GATCGCCTCTGT





GAAA (177)
CCCA (178)





91
chr19:
chr19:
GTGCTTGGAGCC
GTGCTTGGAGCC
3
29
2.91
3.56E−07
3′ss
Br.



55776746-55777253
55776757-55777253
CTGTGCAGACTT
CTGTGCAGCCTG





TCCGCAGGGTGT
GTGACAGACTTT





GCGC (179)
CCGC (180)





92
chr1:
chr1:
GCTGGACACGCT
GCTGGACACGCT
1
14
2.91
2.38E−07
exon
Br.



39332671-39338689
39333282-39338689
GACCAAGGCATC
GACCAAGGTGTT




skip





ACTTAGGAGCTG
GGTAGCCTTATA





CTAC (181)
TGAA (182)





93
chr2:
chr2:
CCCCTGAGATGA
CCCCTGAGATGA
1
14
2.91
1.82E−07
exon
Br.



27260570-27260682
27260570-27261013
AGAAAGAGCTCC
AGAAAGAGCTCC




incl.





CTGTTGACAGCT
TGAGCAGCCTGA





GCCT (183)
CTGA (184)





94
chr2:
chr2:
CTGAACTTTGGG
CTGAACTTTGGG
3
28
2.86
7.09E−06
3′ss
Br.



233599948-233600472
233599948-233612324
CCTGAATGATGT
CCTGAATGGCTC





GTTTGGACCCCG
CGAGCTCTGTCC





AATA (185)
AGTG (186)





95
chr11:
chr11:
AGATCGCCTGGC
AGATCGCCTGGC
0
6
2.81
4.87E−09
3′ss
Br.



3697619-3697738
3697606-3697738
TCAGTCAGTTTT
TCAGTCAGACAT





TCTCTCTAGACA
GGCCAAACGTGT





TGGC (187)
AGCC (188)





96
chr11:
chr11:
GGAGGTGGACCT
GGAGGTGGACCT
0
6
2.81
1.25E−06
3′ss
Br.



68363686-68367788
68363686-68367808
GAGTGAACAATT
GAGTGAACCACC





TCTCCCCTCTTT
CAACTGGTCAGC





TTAG (189)
TAAC (190)





97
chr12:
chr12:
TACAGATGGTAA
TACAGATGGTAA
0
6
2.81
8.19E−07
3′ss
Br.



72315234-72316743
72315234-72316762
AATGCAAGTTTG
AATGCAAGGAAT





ATTTTTCATATC
TGCCACAAGCAG





CAGG (191)
TCTG (192)





98
chr16:
chr16:
CCCTGCTCATCA
CCCTGCTCATCA
0
6
2.81
5.11E−07
3′ss
Br.



685022-685280
684956-685280
CCTACGGGTCTG
CCTACGGGCCCT





TCCCAGGCTCTC
ATGCCATCAATG





TGGG (193)
GGAA (194)





99
chr1:
chr1:
GGCTCCCATTCT
GGCTCCCATTCT
0
6
2.81
3.43E−04
3′ss
Br.



155630724-155631097
155630704-155631097
GGTTAAAGAGTG
GGTTAAAGGCCA





TTCTCATTTCCA
GTCTGCCATCCA





ATAG (195)
TCCA (196)





100
chr1:
chr1:
CTGCACTTATAA
CTGCACTTATAA
0
6
2.81
1.50E−06
3′ss
Br.



47108988-47110832
47108973-47110832
ATATTCAGTGTT
ATATTCAGACCC





CCACCTTGCAGA
GAGGGGAAGCTG





CCCG (197)
CAGC (198)





101
chr22:
chr22:
CGCTGGCACCAT
CGCTGGCACCAT
0
6
2.81
1.29E−02
3′ss
Br.



36627480-36629198
36627512-36629198
GAACCCAGTATT
GAACCCAGAGAG





TCCAGGACCAAG
CAGTATCTTTAT





TGAG (199)
TGAG (200)





102
chr6:
chr6:
CCCTAGTCTGAT
AGAGAAGTCGTT
0
6
2.81
6.01E−04
5′ss
Br.



31919565-31919651
31919381-31919651
TCCTTTAGGTTG
TCATTCAAGTTG





GTGTAATCAGCT
GTGTAATCAGCT





GGGG (201)
GGGG (52)





103
chr1:
chr1:
TTCCCCATCAAC
TTCCCCATCAAC
3
26
2.75
6.26E−07
3′ss
Br.



19480448-19481411
19480433-19481411
ATCAAAAGTTTT
ATCAAAAGTTCC





GTTGTCTGCAGT
AATGGTGGCAGT





TCCA (202)
AAGA (203)





104
chr11:
chr11:
CCAGCTGCATTG
CCAGCTGCATTG
4
32
2.72
6.93E−04
3′ss
Br.



67161081-67161193
67161081-67161161
CAAGTTCGGACT
CAAGTTCGGGGT





GTGAGTCCCTGC
GCGGAAGACTCA





AGGC (204)
CAAC (205)





105
chr12:
chr12:
GGCCAGCCCCCT
GGCCAGCCCCCT
6
41
2.58
1.26E−09
3′ss
Br.



120934019-120934204
120934019-120934218
TCTCCACGGCCT
TCTCCACGGTAA





TGCCCACTAGGT
CCATGTGCGACC





AACC (206)
GAAA (207)





106
chr14:
chr14:
CGCTCTCCGCCT
AGGGAGACGTTC
2
17
2.58
1.96E−05
exon
Br.



75348719-75352288
75349327-75352288
TCCAGAAGGGGT
CCTGCCTGGGGT




skip





CTCCTTATGCCA
CTCCTTATGCCA





GGGA (208)
GGGA (209)





107
chr1:
chr1:
TTGGAAGCGAAT
TTGGAAGCGAAT
1
11
2.58
1.14E−07
3′ss
Br.



23398690-23399766
23398690-23399784
CCCCCAAGTCCT
CCCCCAAGTGAT





TTGTTCTTTTGC
GTATATCTCTCA





AGTG (210)
TCAA (211)





108
chr11:
chr11:
CTACGGCGGTGC
CTACGGCGGTGC
0
5
2.58
1.09E−07
3′ss
Br.



44957237-44958353
44957213-44958353
CCTCCTCACCCC
CCTCCTCAGCAT





CTTTTCATCCCC
CTCCCTGATCAT





CGCC (212)
GTGG (213)





109
chr12:
chr12:
CCTGGTCGCAGT
CCTGGTCGCAGT
0
5
2.58
9.89E−04
exon
Br.



57494682-57496072
57493873-57496072
TCAACAAGATGA
TCAACAAGGAGA




incl.





GGAATCTGATGC
TCCTGCTGGGCC





TCAG (214)
GTGG (215)





110
chr16:
chr16:
CACCAAGCAGAG
CACCAAGCAGAG
0
5
2.58
1.04E−07
3′ss
Br.



15129410-15129852
15129410-15129872
GCTTCCAGTCTG
GCTTCCAGGCCA





TCTGCCCTTTCT
GAAGCCTTTTAA





GTAG (216)
AAGG (217)





111
chr17:
chr17:
GGGACTCCCCCA
GGGACTCCCCCA
0
5
2.58
9.75E−05
3′ss
Br.



41164294-41164946
41164294-41165063
AAGACAAGCTTT
AAGACAAGGTCC





TCTTTCAGTAAA
CATTTTCAGTGC





TGTA (218)
CCAA (219)





112
chr17:
chr17:
GCACTGCTGTTC
GCACTGCTGTTC
0
5
2.58
1.25E−05
3′ss
Br.



61511981-61512446
61511955-61512446
AACCTCGGCTTC
AACCTCGGGGGC





TCCCTTCCTCTC
AAGTATAGCGCA





ACCC (220)
TTTG (221)





113
chr19:
chr19:
ACGAGACCATTG
ACGAGACCATTG
0
5
2.58
1.71E−05
3′ss
Br.



2247021-2247564
2247021-2247592
CCTTCAAGGAGC
CCTTCAAGGTGC





CCTCTCTGTCCC
CGAGCAGAGAGA





CCGC (222)
TCGA (223)





114
chr21:
chr21:
AAGATGTCCCTG
AAGATGTCCCTG
0
5
2.58
5.11E−07
3′ss
Br.



38570326-38572514
38570326-38572532
TGAGGATTGTGT
TGAGGATTGCAC





GTTTGTTTCCAC
TGGGTGCAAGTT





AGGC (224)
CCTG (225)





115
chr6:
chr6:
AGAGAAGTCGTT
AGAGAAGTCGTT
0
5
2.58
2.67E−07
3′ss
Br.



31919381-31919551
31919381-31919651
TCATTCAATCTG
TCATTCAAGTTG





ATTCCTTTAGGT
GTGTAATCAGCT





CAGC (226)
GGGG (52)





116
chrX:
chrX:
AGCCCAGCAGTT
AGCCCAGCAGTT
0
5
2.58
5.15E−07
3′ss
Br.



48751114-48751182
48751100-48751182
CCGAAATGTCTC
CCGAAATGCGCC





CCTTCTCCAGCG
CCCATTCCTGGA





CCCC (227)
GGAC (228)





117
chr17:
chr17:
CCCTCCCCCGGC
ACCCAAGCCTTG
2
16
2.50
3.35E−04
exon
Br.



40714505-40714629
40714237-40714629
TCCTGTCGGCCT
AGGTTTCAGCCT




incl.





GGGCAGCATGGC
GGGCAGCATGGC





CGTA (229)
CGTA (18)





118
chr15:
chr15:
TGATTCCAAGCA
TGATTCCAAGCA
1
10
2.46
1.54E−06
3′ss
Br.



25213229-25219533
25213229-25219457
AAAACCAGCCTT
AAAACCAGGCTC





CCCCTAGGTCTT
CATCTACTCTTT





CAGA (230)
GAAG (231)





119
chr2:
chr2:
CAAGTCCATCTC
CAAGTCCATCTC
2
15
2.42
6.24E−03
3′ss
Br.



132288400-132289224
132288400-132289236
TAATTCAGCCAA
TAATTCAGGCAA





CTCTCAAGGCAA
GGCCAGGCCCCA





GGCC (232)
GCCC (98)





120
chr7:
chr7:
CTATCAAAAGAG
CTATCAAAAGAG
2
15
2.42
9.00E−05
exon
Br.



8267481-8268230
8261028-8268230
GATATGTTCATT
GATATGTTTCTT




incl.





TTAGGAGGCCAA
GTCTCAAGAAGA





GGCA (233)
AAAC (133)





121
chr3:
chr3:
GTCTTCCAATGG
GTCTTCCAATGG
7
41
2.39
2.38E−07
3′ss
Br.



148759467-148759952
148759455-148759952
CCCCTCAGCCTT
CCCCTCAGGAAA





TTCTCTAGGAAA
TGATACACCTGA





TGAT (234)
AGAA (235)





122
chr8:
chr8:
GCACCTCCCCGG
GCACCTCCCCGG
4
25
2.38
3.96E−02
exon
Br.



144873910-144874045
144873610-144874045
GACGCCTGCCCT
GACGCCTGTCAC




incl.





TGTCTGGAAAGA
CGGACTTTGCTG





AGTT (236)
AGGA (237)





123
chr17:
chr17:
TGGACCCCAGAC
GTCCCGGAACCA
1
9
2.32
5.71E−03
exon
Br.



3828735-3831533
3828735-3831956
CACACCGGAAGA
CATGCACGAAGA




incl.





AATGAGCCAGAA
AATGAGCCAGAA





GTGA (238)
GTGA (239)





124
chr11:
chr11:
TCTGTGTTCCCA
TGTATGACGTCA
0
4
2.32
2.08E−03
5′ss
Br.



66040546-66043274
66039931-66043274
TCGCACAGGAAT
CTGACCAGGAAT





CCTACGCCAACG
CCTACGCCAACG





TGAA (240)
TGAA (241)





125
chr12:
chr12:
GGAATATGATCC
GGAATATGATCC
0
4
2.32
6.10E−04
3′ss
Br.



15272132-15273996
15264351-15273996
CACCCTCGTACT
CACCCTCGAATC





TCTCAAAGAGGA
AACCTACCGACA





TGGC (242)
CCAA (243)





126
chr16:
chr16:
GAACTGGCACCG
GAACTGGCACCG
0
4
2.32
1.02E−06
3′ss
Br.



313774-313996
313774-314014
ACAGACAGTGTC
ACAGACAGATCC





CCCTCCCTCCCC
TGTTTCTGGACC





AGAT (244)
TTGG (245)





127
chr19:
chr19:
TGATGAAGACCT
TGATGAAGACCT
0
4
2.32
1.48E−03
3′ss
Br.



44116292-44118380
44112259-44118380
TTCCCCAGATCT
TTCCCCAGGCCC





CTTAGGTGAAGA
CGAGCATTCCTC





CATG (246)
TGAT (247)





128
chr1:
chr1:
CCAGGCCGACAT
CCAGGCCGACAT
0
4
2.32
4.27E−07
3′ss
Br.



228335400-228336058
228335400-228336071
GGAGAGCAGCCC
GGAGAGCAGCAA





CACCCACAGGCA
GGAGCCCGGCCT





AGGA (248)
GTTT (249)





129
chr20:
chr20:
ACATGAAGGTGG
ACATGAAGGTGG
0
4
2.32
5.15E−07
3′ss
Br.



34144042-34144761
34144042-34144743
ACGGAGAGTTCT
ACGGAGAGGTAC





CTGTGACCAGAC
TGAGGACAAATC





ATGA (250)
AGTT (50)





130
chr2:
chr2:
TTCGTCCATATG
TTCGTCCATATG
0
4
2.32
2.38E−03
3′ss
Br.



198267783-198268308
198267759-198268308
TGCATAAGCTTC
TGCATAAGATCC





TTCTCTTTTCTC
TCGTGGTCATTG





TTTT (251)
AACC (252)





131
chr3:
chr3:
AGGGATGGCCAG
AGAAGGGAGCGA
0
4
2.32
8.01E−04
5′ss
Br.



47969840-47981988
47969840-48019354
TGGTAGTGGGTC
TACTACAGGGTC





TCCAACTGAATT
TCCAACTGAATT





CCTT (253)
CCTT (254)





132
chr4:
chr4:
CCAATGTGGTTC
CCAATGTGGTTC
0
4
2.32
1.00E−05
3′ss
Br.



38907482-38910197
38907482-38910212
AAAACACATTAT
AAAACACAGGTA





CTCATCTGCAGG
AAAGTGTCTTAA





GTAA (255)
CTGG (256)





133
chr7:
chr7:
CCATTGATGCAA
CCATTGATGCAA
0
4
2.32
7.45E−03
exon
Br.



94227316-94228086
94218044-94228086
ACGCAGCAATGG
ACGCAGCAGAAC




incl.





AGTTTCGCTCCT
TTGCCACATCAG





GTTG (257)
ACTC (258)





134
chr8:
chr8:
GCTGCATCTGGA
CAGTGTTAGTGA
0
4
2.32
6.84E−03
5′ss
Br.



17873340-17882869
17872349-17882869
GGTCCTGGGAAG
ATGACTATGAAG





CAGAATCTGGTA
CAGAATCTGGTA





ATAT (259)
ATAT (260)





135
chr17:
chr17:
ACAAGGACACAG
ACAAGGACACAG
10
53
2.30
5.76E−06
3′ss
Br.



73518592-73519333
73518292-73519333
AAAACAAGCCTT
AAAACAAGCTGG





CCCACACAGGCC
AGCACCGCTGCA





CTGC (261)
CCTC (262)





136
chr16:
chr16:
AGCTCGGACCAA
AGCTCGGACCAA
9
48
2.29
1.29E−03
3′ss
Br.



47495337-47497792
47495337-47497809
GCGCTCAGTTTT
GCGCTCAGCTTA





AAAATTGCTATA
GCCTGCGACGCT





GCTT (263)
TATG (264)





137
chr6:
chr6:
AGGGGGCTCTTT
AGGGGGCTCTTT
6
32
2.24
3.39E−03
3′ss
Br.



91269953-91271340
91269933-91271340
ATATAATGTTTG
ATATAATGTGCT





TGCCTTTCTTTC
GCATGGTGCTGA





GCAG (265)
ACCA (266)





138
chr15:
chr15:
GCCCCCAACTGA
GCCCCCAACTGA
2
13
2.22
4.76E−03
exon
Br.



41130464-41130740
41128480-41130740
GAAGCTGGGCTG
GAAGCTGGTGCC




incl.





GAGTGCTGTGGC
CTTGGTGTGGTG





ACAA (267)
GAAG (268)





139
chr17:
chr17:
GAACGAGATCTC
AGTATCAGAAGG
4
21
2.14
6.40E−03
5′ss
Br.



2276080-2276246
2275782-2276246
ATCCCACTAACT
ACAAAAAGAACT





ACAAAGAGCTGG
ACAAAGAGCTGG





AGCT (269)
AGCT (270)





140
chr17:
chr17:
TGAAGGTCCAGG
TGAAGGTCCAGG
8
35
2.00
4.45E−02
3′ss
Br.



4885470-4886051
4885455-4886051
GCATGGAGCCTG
GCATGGAGTGTC





TCTCCTGGCAGT
TCTATGGCTGCT





GTCT (271)
ACGT (272)





141
chr16:
chr16:
GGCGGCCGCGCC
GGCGGCCGCGCC
2
11
2.00
3.29E−02
exon
Br.



1728357-1733509
1728357-1735439
GGCTCCAGGAAA
GGCTCCAGGGCC




incl.





TGGCAACTGCTG
ATGAAGCCCCCA





ACAG (273)
GGAG (274)





142
chr11:
chr11:
CCTTCCAGCTAC
CCTTCCAGCTAC
1
7
2.00
1.25E−04
3′ss
Br.



2993509-2997253
2993473-2997253
ATCGAAACGCAT
ATCGAAACTTTA





GAGGATGTTGTA
CCTAAAGCAGTA





TTTC (275)
AAAA (276)





143
chr10:
chr10:
CTTTTCTCTTCT
GATGTGATGAAC
0
3
2.00
2.72E−03
5′ss
Br.



69583150-69595149
69583150-69597691
TTTTATAGGTTG
TATCTTCGGTTG





AACAAATCCTGG
AACAAATCCTGG





CAGA (277)
CAGA (278)





144
chr11:
chr11:
GCACTGGGCATT
GCACTGGGCATT
0
3
2.00
1.28E−07
3′ss
Br.



66053068-66053171
66053007-66053171
CAGAAAAGTCTC
CAGAAAAGGTTC





TCTTCCTCACCC
TCCCCGGAGGTG





CTGC (279)
CTGG (280)





145
chr11:
chr11:
CTGTCACAGGGG
CTGTCACAGGGG
0
3
2.00
2.18E−03
3′ss
Br.



77090454-77090938
77090433-77090938
AGTTTACGTCTT
AGTTTACGGGAA





GCATGTCTCTCT
TGCCAGAGCAGT





TACA (281)
GGGC (282)





146
chr12:
chr12:
GGGTGCAAAAGA
GGGTGCAAAAGA
0
3
2.00
2.66E−07
3′ss
Br.



57032980-57033763
57033091-57033763
TCCTGCAGCCAT
TCCTGCAGGACT





TCCAGGTTGCTG
ACAAATCCCTCC





AGGT (283)
AGGA (284)





147
chr12:
chr12:
GGCACCCCAAAA
GGCACCCCAAAA
0
3
2.00
9.82E−07
3′ss
Br.



58109976-58110164
58109976-58110194
GATGGCAGATCA
GATGGCAGGTGC





GTCTCTCCCTGT
GAGCCCGACCAA





TCTC (285)
GGAT (286)





148
chr17:
chr17:
GCATCTCAGCCC
GCATCTCAGCCC
0
3
2.00
2.72E−07
3′ss
Br.



16344444-16344670
16344444-16344681
AAGAGAAGTTTC
AAGAGAAGGTTA





TTTGCAGGTTAT
TATTCCCAGAGG





ATTC (287)
ATGT (288)





149
chr1:
chr1:
CTTGCCTTCCCA
CTTGCCTTCCCA
0
3
2.00
2.32E−04
3′ss
Br.



154246074-154246225
154246074-154246249
TCCTCCTGCAAA
TCCTCCTGAACT





CACCTGCCACCT
TCCAGGTCCTGA





TTCT (289)
GTCA (290)





150
chr1:
chr1:
CTACACAGAGCT
CTACACAGAGCT
0
3
2.00
8.14E−08
3′ss
Br.



32096333-32098095
32096443-32098095
GCAGCAAGGTGT
GCAGCAAGCTCT





GCACCCAGCTGC
GTCCCAAATGGG





AGGT (291)
CTAC (292)





151
chr2:
chr2:
ACCTGTTACCAC
ACCTGTTACCAC
0
3
2.00
1.17E−04
3′ss
Br.



101622533-101635459
101622533-101622811
TTTCAAAATTTC
TTTCAAAAATCT





TGTGCTAAACAG
ACAGACAGTCAA





TGTT (293)
TGTG (294)





152
chr2:
chr2:
AGACAAGGGATT
AGACAAGGGATT
0
3
2.00
3.82E−06
3′ss
Br.



26437445-26437921
26437430-26437921
GGTGGAAACATT
GGTGGAAAAATT





TTATTTTACAGA
GACAGCGTATGC





ATTG (295)
CATG (296)





153
chr3:
chr3:
CAACGAGAACAA
CAACGAGAACAA
0
3
2.00
2.29E−07
3′ss
Br.



101401353-101401614
101401336-101401614
GCTATCAGTTAC
GCTATCAGGGCT





TTTTACCCCACA
GCTAAGGAAGCA





GGGC (297)
AAAA (298)





154
chr5:
chr5:
TCTATATCCCCT
TCTATATCCCCT
0
3
2.00
1.27E−06
3′ss
Br.



177576859-177577888
177576839-177577888
CTAAGACGCACT
CTAAGACGGACC





TCTTTCCCCTCT
TGGGTGCAGCCG





GTAG (299)
CAGG (300)





155
chr6:
chr6:
TGGAGCCAGTTA
TGGAGCCAGTTA
0
3
2.00
9.28E−04
3′ss
Br.



31506716-31506923
31506632-31506923
CTGGGCAGGTGT
CTGGGCAGGTGT





GTTTTTGTGACA
CTGTACTGGTGA





GTCA (301)
TGTG (302)





156
chrX:
chrX:
AAAAGAAACTGA
AAAAGAAACTGA
13
54
1.97
1.08E−05
3′ss
Br.



129771378-129790554
129771384-129790554
GGAATCAGTATC
GGAATCAGCCTT





ACAGGCAGAAGC
AGTATCACAGGC





TCTG (303)
AGAA (304)





157
chrX:
chrX:
CAGCACTAGGTT
CAGCACTAGGTT
7
30
1.95
8.04E−04
exon
Br.



135758876-135761693
135760115-135761693
ATAAAGAGGAGT
ATAAAGAGAGGA




skip





CTAGTAAAAGCC
TGTCTTATATCT





CTAA (305)
TAAA (306)





158
chr6:
chr6:
GCCCCCGTTTTC
GCCCCCGTTTTC
4
18
1.93
9.28E−05
3′ss
Br.



31936315-31936399
31936315-31936462
CTGCCCAGCCCT
CTGCCCAGTACC





TGTCCTCAGTGC
TGAAGCTGCGGG





ACCC (307)
AGCG (308)





159
chr2:
chr2:
GCCGCCGCCGCC
CACCTTATGAAG
10
40
1.90
4.22E−03
5′ss
Br.



97757449-97760437
97757449-97757599
GCCGCCAGGCTC
TATAGCAGGCTC





TGATGCTGGTGT
TGATGCTGGTGT





CTGG (309)
CTGG (310)





160
chr19:
chr19:
AGTGGCAGTGGC
AGTGGCAGTGGC
6
25
1.89
2.97E−03
3′ss
Br.



6731065-6731209
6731122-6731209
TGTACCAGCCCA
TGTACCAGCTCT





CAGGAAACAACC
TGGTGGAGGGCT





CGTA (311)
CCAC (312)





161
chr16:
chr16:
GAGATTCTGAAG
GAGATTCTGAAG
4
16
1.77
5.02E−05
3′ss
Br.



54954250-54957496
54954322-54957496
ATAAGGAGTTCT
ATAAGGAGGTAA





CTTGTAGGATGC
AACCTGTTTAGA





CACT (313)
AATT (314)





162
chr2:
chr2:
CCAAGAGACAGC
CCCCTGAGATGA
4
16
1.77
3.39E−06
exon
Br.



27260760-27261013
27260570-27261013
ACATTCAGCTCC
AGAAAGAGCTCC




incl.





TGAGCAGCCTGA
TGAGCAGCCTGA





CTGA (315)
CTGA (184)





163
chr10:
chr10:
TCAGAGCAGTCG
CTACGACAGTGA
10
35
1.71
1.55E−02
5′ss
Br.



75290593-75294357
75290593-75296026
GGACACAGGACA
AGATTCAGGACA





CCTGACTGATAG
CCTGACTGATAG





TGAA (316)
TGAA (317)





164
chr1:
chr1:
CTGTTGTGTCCG
CTGTTGTGTCCG
19
63
1.68
5.06E−05
3′ss
Br.



155278867-155279833
155278867-155279854
TTTTGAAGAGCC
TTTTGAAGAATG





CTTTGCTCCTCC
AACGGAGACCAG





CTCA (318)
AATT (319)





165
chr16:
chr16:
CCGGCCCTACAG
CCCTCCGCCTCC
6
21
1.65
3.26E−02
exon
Br.



630972-632882
632309-632882
GCTGGCGGATAA
TGATGCAGATAA




skip





ACCCACTGCCCT
ACCCACTGCCCT





ACAG (320)
ACAG (321)





166
chr16:
chr16:
GAGATTCTGAAG
GAGATTCTGAAG
18
57
1.61
6.30E−07
3′ss
Br.



54954239-54957496
54954322-54957496
ATAAGGAGGATG
ATAAGGAGGTAA





CCACTGGAAATG
AACCTGTTTAGA





TTGA (322)
AATT (314)





167
chr14:
chr14:
TGAAAAGTCCAG
TCCTGGAGGAGC
15
47
1.58
1.41E−02
5′ss
Br.



39734625-39746137
39736726-39746137
AGGAAGAGGTTG
TACGCAGGGTTG





TGGCAGCACTGC
TGGCAGCACTGC





CTGA (323)
CTGA (324)





168
chr13:
chr13:
GTCATGGCAGAA
CTATAGCTACTG
10
32
1.58
1.25E−02
exon
Br.



21157158-21165105
21164006-21165105
GACCTCCATCCA
GATATGGGTCCA




skip





AGACATCTCTGG
AGACATCTCTGG





CATC (325)
CATC (326)





169
chr17:
chr17:
CCGGAGCCCCTT
CCGGAGCCCCTT
5
17
1.58
4.45E−02
3′ss
Br.



45229302-45232037
45229284-45232037
CAAAAAAGACTT
CAAAAAAGTCTG





TTCGTGTTTTAC
TTGCCAGAATCG





AGTC (327)
GCCA (328)





170
chr16:
chr16:
CCACAGATACTA
CCACAGATACTA
3
11
1.58
1.99E−02
3′ss
Br.



47484364-47485306
47462809-47485306
TTAGGAGGCCAT
TTAGGAGGGAAT





ACCACCCTGAAC
TTATCATGGCAT





GCGC (329)
CCAG (330)





171
chr12:
chr12:
TGTTCAAGTTCC
CCTGGTCGCAGT
1
5
1.58
1.50E−04
exon
Br.



57493873-57494628
57493873-57496072
CAAAGCAGGAGA
TCAACAAGGAGA




incl.





TCCTGCTGGGCC
TCCTGCTGGGCC





GTGG (331)
GTGG (215)





172
chr16:
chr16:
ACTCCCAGCTCA
ACTCCCAGCTCA
0
2
1.58
6.10E−05
3′ss
Br.



56403209-56419830
56403239-56419830
ATGCAATGGTTC
ATGCAATGGCTC





CATACCATCTGG
ATCAGATTCAAG





TACT (332)
AGAT (333)





173
chr17:
chr17:
ATCACTGTGACT
ATCACTGTGACT
0
2
1.58
4.98E−05
3′ss
Br.



80013701-80013861
80013701-80013876
TCCCTGAGGTCT
TCCCTGAGCTGC





CTGCTCCTCAGC
TGTCCCCCAGCA





TGCT (334)
ACGT (335)





174
chr18:
chr18:
ATCCTCTCAATC
ATCCTCTCAATC
0
2
1.58
4.76E−02
3′ss
Br.



51729496-51731367
51715381-51731367
AAAATAAGTTTG
AAAATAAGGGTA





TGTGCACTTTTC
AACCAGACTTGA





TGCT (336)
ATAC (337)





175
chr1:
chr1:
CTATTCCTTTAT
CTATTCCTTTAT
0
2
1.58
5.34E−04
3′ss
Br.



145109684-145112354
145109684-145112372
TGAATTTGTTTT
TGAATTTGATAC





CTTCATCATTCT
TTTCATTCAGAA





AGAT (338)
AACC (339)





176
chr2:
chr2:
AGTCATACCTGG
AGTCATACCTGG
0
2
1.58
3.46E−03
3′ss
Br.



242274627-242275373
242274627-242275389
AGCAGCAGTTTG
AGCAGCAGAAAA





TTTCTTTTCTAG
AATTGAAAGAAC





AAAA (340)
TGTC (341)





177
chr3:
chr3:
GCAACCAGTTTG
GCAACCAGTTTG
0
2
1.58
1.37E−04
3′ss
Br.



49395199-49395459
49395180-49395459
GGCATCAGCTGC
GGCATCAGGAGA





CCTTCTCTCCTG
ACGCCAAGAACG





TAGG (342)
AAGA (343)





178
chr4:
chr4:
CCATGGTCAAAA
CCATGGTCAAAA
0
2
1.58
3.60E−05
3′ss
Br.



152022314-152024139
152022314-152024022
AATGGCAGCACC
AATGGCAGACAA





AACAGGTCCGCC
TGATTGAAGCTC





AAAT (344)
ACGT (345)





179
chr5:
chr5:
GCCTGATGCCCG
GCCTGATGCCCG
0
2
1.58
1.29E−02
exon
Br.



1323984-1325865
1324928-1325865
AATTTCAGGCCA
AATTTCAGTTTG




skip





TGAAGTACTTGT
GCACTTACAGCG





CATA (346)
AATC (347)





180
chr5:
chr5:
AGATTGAAGCTA
AGATTGAAGCTA
0
2
1.58
6.18E−06
3′ss
Br.



132439718-132439902
132439718-132439924
AAATTAAGTTTT
AAATTAAGGAGC





CTGTCTTACCCA
TGACAAGTACTT





TTCC (348)
GTAG (349)





181
chr5:
chr5:
AGCACAAGCTAT
AGCACAAGCTAT
0
2
1.58
5.76E−06
3′ss
Br.



44813384-44814996
44813384-44815014
GTATCAAGCATA
GTATCAAGGATT





ACTTTCTTCTAC
CTGGAGTGAAGC





AGGA (350)
AGAT (351)





182
chr6:
chr6:
AGATGTAAAAGT
AGATGTAAAAGT
0
2
1.58
5.43E−04
3′ss
Br.



52546712-52548863
52546712-52548875
GTCACTGTTTTG
GTCACTGTTTAC





GTTTTCAGTTAC
AGCTTTCTTCCT





AGCT (352)
GGCT (353)





183
chr7:
chr7:
CTGCAGCCTCCG
CCATTGATGCAA
0
2
1.58
8.78E−03
exon
Br.



94218044-94227241
94218044-94228086
CCTCCCAGGAAC
ACGCAGCAGAAC




incl.





TTGCCACATCAG
TTGCCACATCAG





ACTC (354)
ACTC (258)





184
chr15:
chr15:
AGGATGATGCAG
AGGATGATGCAG
10
28
1.40
1.70E−03
3′ss
Br.



59373483-59376300
59373483-59376327
CATCCAACTGGT
CATCCAACGCGG





CTTTTTGTGTTC
GCACATGAACGC





TGTG (355)
CCCC (356)





185
chr1:
chr1:
TGGTGAAATGGA
TGGTGAAATGGA
12
33
1.39
1.25E−03
3′ss
Br.



153925126-153925280
153925111-153925280
CCCCAAAGTCTT
CCCCAAAGTACC





TCTCTTTCAAGT
TGCTATTGAGGA





ACCT (357)
GAAC (358)





186
chr1:
chr1:
AGCTTAAAGAAC
GATCAAGGCAAC
9
25
1.38
3.31E−02
exon
Br.



151739775-151742647
151740709-151742647
TGTATTCGTTTG
CGGGAAAGTTTG




skip





ACTGCAACCCTG
ACTGCAACCCTG





GAGT (359)
GAGT (360)





187
chr19:
chr19:
AACACACCAACT
AACACACCAACT
1
4
1.32
8.52E−04
3′ss
Br.



47342877-47349249
47342835-47349249
TTGTGGAGGTCC
TTGTGGAGTTCC





TGGCAATCTCCG
GGAACTTTAAGA





TTGC (361)
TCAT (362)





188
chr15:
chr15:
GCGGGTCTGCAG
GTTCCAGGTCCT
5
13
1.22
5.55E−04
exon
Br.



75631685-75632305
75632219-75632305
CCTACGCAAACT
CCTGGCAGAACT




skip





GAAGCAGGCCCA
GAAGCAGGCCCA





GACC (363)
GACC (364)





189
chr1:
chr1:
CCCGCTGCCCCA
ATTCTGATATAG
5
13
1.22
1.52E−02
exon
Br.



212459633-212506838
212502673-212506838
GCTCAAAGATCA
TAAAAATGATCA




skip





GTGCTAACATCT
GTGCTAACATCT





TCCG (365)
TCCG (366)





190
chr22:
chr22:
ATGAGTTTCCCA
ATGAGTTTCCCA
2
6
1.22
1.59E−03
3′ss
Br.



30976673-30976998
30976688-30976998
CCGATGGGGAGG
CCGATGGGGAGA





AAGACCGCAGGA
TGTCAGCGCAGG





AGGA (367)
AGGA (368)





191
chr7:
chr7:
AGTTTATTTAAC
AGTTTATTTAAC
2
6
1.22
3.40E−02
exon
Br.



80535232-80545994
80458061-80545994
ATTTGATGAGCC
ATTTGATGAACT




incl.





TACCTTGTACAA
TCGAGAAACCAA





TGCT (369)
GACC (370)





192
chr8:
chr8:
CCACCTAGCAGC
CCACCTAGCAGC
2
6
1.22
1.17E−03
intron
Br.



145153766-145153768
145153691-145153768
CACCAGAGACCA
CACCAGAGGTTA




reten-





GAGGTGGCACAG
CAAGGGGAGAGT




tion





GCAG (371)
GGCC (372)





193
chr9:
chr9:
TCCAGGATCCTG
GGCAGCGGAGGG
2
6
1.22
8.61E−03
exon
Br.



96285645-96289436
96278551-96289436
AGGCATGGCCAT
GCGACAAACCAT




incl.





ATCAGCGGGAAC
ATCAGCGGGAAC





AAGA (373)
AAGA (374)





194
chr2:
chr2:
GGCAACTTCGTT
GGCAACTTCGTT
20
47
1.19
5.26E−03
3′ss
Br.



106781255-106782511
106781240-106782511
AATATGAGCTTT
AATATGAGGTCT





CTACTCAACAGG
ATCCAGGAAAAT





TCTA (375)
GGTG (376)





195
chr19:
chr19:
GGAGCCTGGGCA
GGAGCCTGGGCA
6
15
1.19
1.98E−02
3′ss
Br.



7976215-7976299
7976215-7976320
TCTCGTTGCCCT
TCTCGTTGGTGG





GCCCGTCTCCCT
AGCTGGCAACAG





CCCA (377)
GACA (378)





196
chr11:
chr11:
CTGGTGTGCTTG
CTGGTGTGCTTG
3
8
1.17
4.87E−02
exon
Br.



9161795-9163486
9161401-9163486
GGAGCCAGGGTT
GGAGCCAGAGAT




incl.





ATCATGAAGATT
CACCTCCTACAC





AAAT (379)
CACT (380)





197
chr1:
chr1:
ATTGGAGGAGCT
ATTGGAGGAGCT
10
23
1.13
3.12E−03
exon
Br.



160252899-160254844
160253429-160254844
TCTGGAAAGATG
TCTGGAAAGTGC




skip





CCCTCTTCGCTT
TCTTGATGATTT





CCCA (381)
CGAT (382)





198
chr19:
chr19:
AATGACGTGCTG
AATGACGTGCTG
7
16
1.09
1.69E−02
3′ss
Br.



16641724-16643408
16641691-16643408
CACCACTGGGCC
CACCACTGCCAG





CTGACGCGCGGA
CGCAAGCAGGCC





AAGT (383)
CGGG (384)





199
chr3:
chr3:
GCCTGGGGTGGA
GCCTGGGGTGGA
9
20
1.07
3.01E−02
exon
Br.



39141945-39142237
39141994-39142237
GAGGGCAGCCCC
GAGGGCAGTCTG




skip





CCAGCTACCACA
GGATGTGGCATT





AGAA (385)
GGCT (386)





200
chr2:
chr2:
GGAAATGGGACA
GGAAATGGGACA
11
24
1.06
3.05E−03
3′ss
Br.



230657846-230659894
230657861-230659894
GGAGGCAGAGGA
GGAGGCAGCTTT





TCACAGGCTTTA
TCTCTCAACAGA





AAAT (387)
GGAT (388)





201
chr10:
chr10:
AGACCGACTGCC
AGACCGACTGCC
5
11
1.00
2.09E−02
exon
Br.



123718925-123719872
123719110-123719872
AGTAATAGGAGA
AGTAATAGAGCC




skip





TTGTGAAGACCT
TGTTAGTATTAA





TTGA (389)
TGAA (390)





202
chr1:
chr1:
TCATGCTAGCCG
TCATGCTAGCCG
5
11
1.00
3.31E−02
exon
Br.



44064584-44067741
44064584-44069086
AGGCCCAGTGGC
AGGCCCAGGAAA




incl.





GGCCAGAGGAGT
CCACTATCAGCG





CCGA (391)
GCCT (392)





203
chr1:
chr1:
GAAGGCAGCTGA
GAAGGCAGCTGA
4
9
1.00
1.37E−03
3′ss
Br.



11131045-11132143
11131030-11132143
GCAAACAGTTCT
GCAAACAGCTGC





CTCCCTTGCAGC
CCGGGAACAGGC





TGCC (393)
AAAG (394)





204
chr6:
chr6:
GCCAACAGCCAA
GCCAACAGCCAA
3
7
1.00
6.32E−03
exon
Br.



109690220-109697276
109691670-109697276
TTCTACAGGTAC
TTCTACAGCTAA




skip





AACAAATAACAC
ACCCACAGTTCA





TGTG (395)
GCCC (396)





205
chr17:
chr17:
CCCATCAACTGC
CCCATCAACTGC
2
5
1.00
4.46E−02
exon
Br.



37873733-37879571
37873733-37876039
ACCCACTCCCCT
ACCCACTCCTGT




skip





CTGACGTCCATC
GTGGACCTGGAT





ATCT (397)
GACA (398)





206
chr17:
chr17:
GCGGAAAGAATT
GCGGAAAGAATT
2
5
1.00
4.49E−02
3′ss
Br.



5250220-5253766
5250220-5253745
GCATGAAGAGCG
GCATGAAGTTTG





ACAACAACACAA
CCATCTCTTGGA





CCAG (399)
GCAA (400)





207
chr1:
chr1:
TGTGGGAATTAC
AAGAAGGGATGG
2
5
1.00
7.58E−03
exon
Br.



27260910-27267947
27250657-27267947
AATTCAAGCTTA
CAGAGAAGCTTA




incl.





TCACACAGACTT
TCACACAGACTT





TCAG (401)
TCAG (402)





208
chr5:
chr5:
CTTCCTCAAGTC
CTTCCTCAAGTC
1
3
1.00
1.35E−02
3′ss
Br.



176759270-176761284
176759247-176761284
GCCCAAAGCTCC
GCCCAAAGACAA





CCCGTTTCTTCT
CGTGGACGACCC





CCCC (403)
CACG (404)





209
chr7:
chr7:
TCTTCGCTGGTG
TCTTCGCTGGTG
1
3
1.00
8.43E−03
exon
Br.



44619227-44621047
44620838-44621047
GCAAACTGTATC
GCAAACTGCGGG




skip





GTGAAGAGCGCT
TGCATCTCGACA





TCCG (405)
TCCA (406)





210
chr1:
chr1:
GCAAGAAGTACA
GCAAGAAGTACA
0
1
1.00
9.69E−03
3′ss
Br.



165619201-165620230
165619201-165620250
AAGTGGAGTATG
AAGTGGAGTATC





TGCTTTGTTGTG
CTATCATGTACA





ACAG (407)
GCAC (408)





211
chr3:
chr3:
TGTAGGAGCAAT
TGTAGGAGCAAT
0
1
1.00
2.54E−04
3′ss
Br.



42826828-42827519
42826812-42827519
GACTGTTGCATT
GACTGTTGGTAT





CTTTTTCTTTAG
GGGCTATTCCAT





GTAT (409)
GTAT (410)





212
chr8:
chr8:
CCTTCCTGGATC
AAGTGCAGATAG
0
1
1.00
5.33E−04
exon
Br.



117738411-117746515
117738411-117767904
CCCCTAAGGTGG
ATGGCCTTGTGG




incl.





TATTAAAGATAA
TATTAAAGATAA





TCAA (411)
TCAA (412)





213
chrX:
chrX:
CAGGTCTAACTC
CAGGTCTAACTC
0
1
1.00
1.53E−02
3′ss
Br.



54835809-54836550
54835809-54836154
GCTTCCAGGCCC
GCTTCCAGGCTG





CAGCAGATGAAC
AAGCTTCAGAAA





CTGA (413)
AGGA (414)





214
chr16:
chr16:
CCTCCCCATACC
GCCTGCCCCGGA
10
20
0.93
3.40E−02
exon
Br.



30012361-30016541
30012851-30016541
TGAGCTCGATGG
AACTCAAGATGG




skip





CGGTGGGACCCC
CGGTGGGACCCC





CCGA (415)
CCGA (82)





215
chr6:
chr6:
GCAAAAGGATAT
GCAAAAGGATAT
10
20
0.93
2.78E−02
3′ss
Br.



43006222-43006303
43006210-43006303
ACCAGGAGCATT
ACCAGGAGGGGT





TATTTCAGGGGT
CCTCAAGATTCG





CCTC (416)
AGAT (417)





216
chr6:
chr6:
CACTCCAATTTA
CACTCCAATTTA
9
18
0.93
1.40E−02
exon
Br.



135517140-135518098
135517140-135520045
TAGATTCTGATT
TAGATTCTTTCT




incl.





CTTCATCATGGT
TAAACACTTCCA





GTGA (418)
GTAA (419)





217
chr7:
chr7:
TGAGAGTCTTCA
TGAGAGTCTTCA
45
85
0.90
3.07E−04
3′ss
Br.



99943591-99947339
99943591-99947421
GTTACTAGTTTG
GTTACTAGAGGC





TCTTTCCTAGAT
GGATTTCCCTGA





CCAG (420)
CTGA (421)





218
chr12:
chr12:
TTAACAGCATTT
CCCAGTCATTCA
10
19
0.86
1.21E−02
intron
Br.



111085013-111085015
111082934-111085015
TGTTTTGCGATT
ACAGGAAGGATT




reten-





CCTGCCAGCTCC
CCTGCCAGCTCC




tion





CAGG (422)
CAGG (423)





219
chr4:
chr4:
GATGAATGCTGA
GATGAATGCTGA
4
8
0.85
2.40E−02
exon
Br.



141300346-141302115
141300346-141300722
CATGGATGATCT
CATGGATGCAGT




skip





CTCTGCAAGAGT
TGATGCTGAAAA





AGAT (424)
TCAA (425)





220
chr10:
chr10:
GTCAATGCTTCC
GTCAATGCTTCC
18
33
0.84
3.71E−02
3′ss
Br.



114905856-114910741
114905856-114910756
ATGTCCAGCTTT
ATGTCCAGGTTC





CTGTCTTCTAGG
CCTCCCCATATG





TTCC (426)
GTCC (427)





221
chr16:
chr16:
TATGGCAAGGAG
TATGGCAAGGAG
7
13
0.81
2.25E−02
3′ss
Br.



30767593-30767675
30767593-30767687
GTCGACCTTCTC
GTCGACCTCTGG





TTTCCCAGCTGG
GCCTGTGGGGTG





GCCT (428)
ATCT (429)





222
chr3:
chr3:
TGGTTTTACCTC
TGGTTTTACCTC
7
13
0.81
5.98E−03
3′ss
Br.



128890351-128890476
128890381-128890476
GGATAGAGACAT
GGATAGAGGTTT





TTGTTATCGCTG
CCAGTTTGTTTC





TGGT (430)
CTCG (431)





223
chr1:
chr1:
GAATCCGTATCT
GAATCCGTATCT
34
60
0.80
2.74E−04
3′ss
Br.



155278756-155279833
155278756-155279854
GGGAACAGAGCC
GGGAACAGAATG





CTTTGCTCCTCC
AACGGAGACCAG





CTCA (432)
AATT (433)





224
chr20:
chr20:
TCCAGGAGTTCC
TTTGACTAGGGT
22
39
0.80
1.59E−02
exon
Br.



264722-270899
264722-270199
AGGTTCCGTGTT
CCAACCAGTGTT




skip





TCACTTCAAGCC
TCACTTCAAGCC





CACT (434)
CACT (435)





225
chr1:
chr1:
GGGCCTGATGAA
GGGCCTGATGAA
30
52
0.77
2.84E−03
exon
Br.



53370762-53373539
53372283-53373539
TGACATCGCTTC
TGACATCGCAGC




skip





CTCGGCAGTCAT
CTTCCCTGCACC





GGGA (436)
CACC (437)





226
chr4:
chr4:
AGCCCCAGGATG
AGCCCCAGGATG
16
28
0.77
1.45E−02
exon
Br.



5815889-5825343
5815889-5819937
CCTCGCAGCTCT
CCTCGCAGACGT




skip





CGGAAGAACTGG
GCCTTCTGCCAT





TTGT (438)
GATT (439)





227
chr20:
chr20:
ACTTGCCTGTGA
ACTTGCCTGTGA
15
26
0.75
1.83E−03
3′ss
Br.



47741142-47752369
47741124-47752369
ATTTCGAGTCTT
ATTTCGAGGTGG





TCCCTCTGAAAC
CCCGGGAGAGTG





AGGT (440)
GCCC (441)





228
chrX:
chrX:
TACCCGGGACAA
TACCCGGGACAA
2
4
0.74
4.57E−02
3′ss
Br.



48933637-48934088
48933604-48934088
CCCCAAGGCCGC
CCCCAAGGGGCT





CCACCCCACCCC
CTGTGACCTCTG





CCAT (442)
CCCC (443)





229
chr1:
chr1:
CATAGTGGAAGT
CATAGTGGAAGT
39
64
0.70
4.20E−07
3′ss
Br.



67890660-67890765
67890642-67890765
GATAGATCTTCT
GATAGATCTGGC





TTTTCACATTAC
CTGAAGCACGAG





AGTG (444)
GACA (445)





230
chr1:
chr1:
GCTGTACCTTCA
GCTGTACCTTCA
18
29
0.66
2.84E−03
3′ss
Br.



156705701-156706410
156705701-156706423
GGAACAGGCCCT
GGAACAGGGTTT





TTCTCCCAGGTT
CCATGCTGAGCT





TCCA (446)
CCTG (447)





231
chr10:
chr10:
TAAAGCGACTCA
TAAAGCGACTCA
29
46
0.65
1.78E−02
exon
Br.



101507147-101514285
101507147-101510125
TTGAGCAGGAGG
TTGAGCAGGCAA




skip





TGGTATAACAGA
AAGGCAGGATTG





CAGA (448)
TGGT (449)





232
chr12:
chr12:
TGGGAATCTGGC
TGGGAATCTGGC
31
49
0.64
3.09E−04
3′ss
Br.



117595889-117603289
117595868-117603289
CAGAGAAGTCTT
CAGAGAAGGTGC





TCTGTCTTGTTT
TTGACATCCTCC





TGAA (450)
AGCA (451)





233
chr2:
chr2:
AGAAAACATCGA
AGAAAACATCGA
8
13
0.64
2.66E−02
exon
Br.



114472772-114476730
114475427-114476730
ATTCAGAGCTTG
ATTCAGAGAGTT




skip





ATAATGGAACTA
CCAGAAGACAGC





TACA (452)
GAAC (453)





234
chr11:
chr11:
CGTCCGCCAGTC
AGCCGGGCGTTG
34
53
0.63
1.78E−02
5′ss
Br.



504996-507112
504996-506608
GTCCCGAGGCAT
GGGGAAAGGCAT





GAAGAACTCTTG
GAAGAACTCTTG





ACTG (454)
ACTG (455)





235
chrX:
chrX:
ACTAATCTTCAG
CAAACACCTCTT
14
22
0.62
2.22E−04
exon
Br.



123224814-123227867
123224614-123227867
CATGCCATTCGG
GATTATAATCGG




incl.





CGTGGCACAAGC
CGTGGCACAAGC





CTAA (456)
CTAA (457)





236
chr9:
chr9:
CACCACAAAATC
CACCACAAAATC
37
57
0.61
6.00E−04
3′ss
Br.



140622981-140637822
140622981-140637843
ACAGACAGCTTG
ACAGACAGCAGC





CTTGCCTTTTGT
TGCAGTATCTCG





TTTA (458)
GAAG (459)





237
chr2:
chr2:
CTCCTACTACAC
AGAGCTCAAAGA
34
52
0.60
2.66E−02
exon
Br.



152324660-152325154
152325065-152325154
AATCTAAGATTT
AGTGTTTAATTT




skip





CAGAAATGGCCA
CAGAAATGGCCA





AAGA (460)
AAGA (461)





238
chr12:
chr12:
ATTTCCAGAGGA
ATTTCCAGAGGA
49
74
0.58
1.10E−04
3′ss
Br.



95660408-95663814
95660408-95663826
TTTACACTTTTG
TTTACACTGGTC





CTTGACAGGGTC
AGTGCTGCTTGC





AGTG (462)
CCAT (463)





239
chr7:
chr7:
GAGTCGGCGCCG
CACAGAGAGCTG
5
8
0.58
4.45E−02
exon
Br.



44880611-44887567
44880611-44882875
AGAACATGTTTC
GGCTACAGTTTC




skip





CTGTGGGCCGCA
CTGTGGGCCGCA





TCCA (464)
TCCA (465)





240
chr10:
chr10:
TGACGTTCTCTG
TGACGTTCTCTG
46
68
0.55
4.09E−04
3′ss
Br.



75554088-75554298
75554088-75554313
TGCTCCAGTGGT
TGCTCCAGGTTC





TTCTCCCACAGG
CCGGCCCCCAAG





TTCC (466)
TCGC (467)





241
chrX:
chrX:
CAAACACCTCTT
CAAACACCTCTT
14
21
0.55
2.21E−02
exon
Br.



123224614-123224703
123224614-123227867
GATTATAACACG
GATTATAATCGG




incl.





CAGGTAACATGG
CGTGGCACAAGC





ATGT (468)
CTAA (457)





242
chr2:
chr2:
TACTCCAGCTTC
TACTCCAGCTTC
30
44
0.54
8.18E−03
3′ss
Br.



86398468-86400772
86398435-86400772
AGCAACAGCACC
AGCAACAGCAGG





TACAGAAGCGGC
TGATACCCTGTC





TCAA (469)
GGTC (470)





243
chr17:
chr17:
TCTCAGCTGACG
GGCATGCAACCA
13
19
0.51
4.21E−03
exon
Br.



47882807-47888837
47886570-47888837
AATGCAAGGCAC
GGCACCAGGCAC




skip





CAACGGAGAGAC
CAACGGAGAGAC





AGCT (471)
AGCT (472)





244
chr1:
chr1:
TCAAATCATTTA
TCAAATCATTTA
9
13
0.49
3.77E−02
3′ss
Br.



109743522-109745534
109743522-109745565
CCTCCAAGCAGC
CCTCCAAGAGGA





CAGCTCCTGTCA
CTCCTGATGGAT





CCAT (473)
TTGA (474)





245
chr11:
chr11:
AGCAAAAAGGGG
AGCAAAAAGGGG
35
49
0.47
2.40E−02
3′ss
Br.



502249-504823
502181-504823
TGTCTCAGAATC
TGTCTCAGGCCA





TCCGGCCTGTGA
CTCTTCACCTCC





AACT (475)
ACCA (476)





246
chr6:
chr6:
TGTTGCCTCCGC
TGGTCATGGCCA
44
60
0.44
5.91E−04
exon
Br.



31611971-31612083
31611971-31612301
GGCCGCAGGACA
AACCCTGGGACA




incl.





GCAGGTGCCAGG
GCAGGTGCCAGG





CTTC (477)
CTTC (478)





247
chr20:
chr20:
TGCCTAAGGCGG
TGCCTAAGGCGG
63
84
0.41
4.16E−05
3′ss
Br.



30310151-30310420
30310133-30310420
ATTTGAATCTCT
ATTTGAATAATC





TTCTCTCCCTTC
TTATCTTGGCTT





AGAA (479)
TGGA (480)





248
chr6:
chr6:
TGGTCATGGCCA
TGGTCATGGCCA
51
68
0.41
4.27E−03
exon
Br.



31612191-31612301
31611971-31612301
AACCCTGGGCTC
AACCCTGGGACA




incl.





CACCCTCATCCA
GCAGGTGCCAGG





GCTG (481)
CTTC (478)





249
chr10:
chr10:
TGCAGATTCCAA
CCTTCCACCCAA
49
63
0.36
4.56E−02
exon
Br.



34649187-34661425
34649187-34663801
AAGAAACGAAAG
GGGAACTGAAAG




incl.





CAGAAGATGAGG
CAGAAGATGAGG





ATAT (482)
ATAT (483)





250
chr4:
chr4:
AGGAGGGCCCCC
AGGAGGGCCCCC
43
54
0.32
1.35E−02
3′ss
Br.



860289-860743
860322-860743
TGCCGCTGGCAA
TGCCGCTGCTGA





CAACTCCCAGCC
CCCCTTTGGCCC





CTGC (484)
GCTT (485)





251
chr8:
chr8:
AACAACTGCCCA
AACAACTGCCCA
3
4
0.32
4.44E−02
3′ss
Br.



99054946-99057170
99055003-99057170
GCTTTGAGTGGC
GCTTTGAGGAAA





AATAATATTGAA
TCTGAAATAGAG





CTGG (486)
TACT (487)





252
chr8:
chr8:
GTTGTGCCCATG
GTTGTGCCCATG
66
81
0.29
4.37E−02
exon
Br.



48694815-48694938
48691654-48694938
ACCTCCAGGTTA
ACCTCCAGTGAT




incl.





GGATTAATTGAG
CCCAGGGCACCG





TGGC (488)
CCGT (489)





253
chr20:
chr20:
GTTAATGGGTTT
GTTAATGGGTTT
57
68
0.25
2.24E−02
exon
Br.



57470739-57473995
57470739-57478585
AATGGAGAGGGC
AATGGAGATGAG




incl.





GGCGAAGAGGAC
AAGGCAACCAAA





CCGC (490)
GTGC (491)





254
chr20:
chr20:
GCAAGGAGCAAC
GTTAATGGGTTT
59
69
0.22
4.34E−03
exon
Br.



57474040-57478585
57470739-57478585
AGCGATGGTGAG
AATGGAGATGAG




incl.





AAGGCAACCAAA
AAGGCAACCAAA





GTGC (492)
GTGC (491)





255
chr19:
chr19:
AGTTTGAGATGA
AGTTTGAGATGA
79
91
0.20
2.28E−02
exon
Br.



17339118-17339611
17339118-17339817
AGCGAATGGATC
AGCGAATGCTCC




incl.





CTGGCTTCCTGG
CCCTACCAGGGG





ACAA (493)
TCGC (494)





256
chrX:
chrX:
AGAAACCTTGAA
AGAAACCTTGAA
84
95
0.18
4.29E−02
exon
Br.



2209644-2326785
2310515-2326785
CGACAAAGTGGA
CGACAAAGAGAC




skip





ATTTTTATACTG
GTGAGTCTTGCT





TGAC (495)
GTGT (496)





257
chrY:
chrY:
AGAAACCTTGAA
AGAAACCTTGAA
84
95
0.18
4.29E−02
exon
Br.



2159644-2276785
2260515-2276785
CGACAAAGTGGA
CGACAAAGAGAC




skip





ATTTTTATACTG
GTGAGTCTTGCT





TGAC (495)
GTGT (496)





258
chr11:
chr11:
ACCCCTTTGGCA
ACCCCTTTGGCA
0
60
5.93
5.12E−05
3′ss
CLL



67815439-67815553
67815439-67816345
TCGATCCTGCCC
TCGATCCTATTT





TTTCCTCAGCAC
GGAGCCTGGCTG





AAGA (497)
CCAA (498)





259
chr2:
chr2:
TGGGAGGAGCAT
TGGGAGGAGCAT
0
59
5.91
7.08E−07
3′ss
CLL



97285513-97297048
97285499-97297048
GTCAACAGAGTT
GTCAACAGGACT





TCCCTTATAGGA
GGCTGGACAATG





CTGG (9)
GCCC (10)





260
chr10:
chr10:
TAAAGTGTTGGC
TAAAGTGTTGGC
0
51
5.70
5.10E−07
3′ss
CLL



93244412-93244921
93244412-93244936
TTTACTTAAATT
TTTACTTAATAC





TATCTTTACAGA
TGCAAACAATTT





TACT (499)
AGTT (500)





261
chr21:
chr21:
ACCTCGTCAGAA
ACCTCGTCAGAA
0
48
5.61
2.38E−05
3′ss
CLL



47970657-47971529
47970657-47971546
ACAACCAGAGTT
ACAACCAGAGGT





CCCCCGTTTCTA
TGGACCAGCCTC





GAGG (501)
AATG (502)





262
chr22:
chr22:
TCATCCAGAGCC
TCATCCAGAGCC
0
48
5.61
3.58E−03
3′ss
CLL



50966161-50966940
50966146-50966940
CAGAGCAGGGGA
CAGAGCAGATGC





TGTCTGACCAGA
AAGTGCTGCTGG





TGCA (173)
ACCA (174)





263
chr13:
chr13:
AAAGATTTCAGA
AAAGATTTCAGA
0
39
5.32
1.50E−02
3′ss
CLL



26970491-26971275
26970491-26971289
AGAAATACTATT
AGAAATACGTAT





TCTCTTTCAGGT
ACCAACTGCAGC





ATAC (503)
CTTA (504)





264
chr5:
chr5:
CCAAAAGAGGGG
CTCCATGCTCAG
0
39
5.32
4.28E−05
exon
CLL



865696-869359
865696-870587
ATAATGAGGGAA
CTCTCTGGGGAA




incl.





GGTGAAGAAGGA
GGTGAAGAAGGA





GCTG (505)
GCTG (129)





265
chr22:
chr22:
CTCTCTCCAACC
CTCTCTCCAACC
0
38
5.29
4.92E−04
3′ss
CLL



39064137-39066874
39064137-39066888
TGCATTCTCATC
TGCATTCTTTGG





TCGCCCACAGTT
ATCGATCAACCC





GGAT (140)
GGGA (141)





266
chr10:
chr10:
TCATCTTGAAAA
TCATCTTGAAAA
0
34
5.13
3.62E−05
3′ss
CLL



89519557-89527429
89516679-89527429
ATGAAAATTCCT
ATGAAAATGTGG





ATTTTACAGCTG
ATAGGCATGTAG





AGGA (506)
ACCT (507)





267
chr20:
chr20:
TTTGCAGGGAAT
TTTGCAGGGAAT
0
34
5.13
3.01E−05
3′ss
CLL



35282126-35284762
35282104-35284762
GGGCTACATCCC
GGGCTACATACC





CTTGGTTCTCTG
ATCTGCCAGCAT





TTAC (35)
GACT (36)





268
chr10:
chr10:
ACCCTGTCTACC
ACCCTGTCTACC
1
64
5.02
4.28E−05
3′ss
CLL



102276734-102286155
102276717-102286155
AGCCTGTGTTTT
AGCCTGTGGATA





CTGCCACCTACA
GACCATGAAGCT





GGAT (508)
GAAG (509)





269
chr14:
chr14:
AGATGTCAGGTG
AGATGTCAGGTG
1
62
4.98
8.04E−09
3′ss
CLL



75356052-75356580
75356052-75356599
GGAGAAAGCCTT
GGAGAAAGCTGT





TGATTGTCTTTT
TGGAGACACAGT





CAGC (89)
TGCA (90)





270
chr19:
chr19:
TGACACAGCCCT
TGACACAGCCCT
1
59
4.91
4.19E−04
3′ss
CLL



16264018-16265147
16264018-16265208
GCAGGCAGGGTC
GCAGGCAGAAGG





CGTGCAGGACCT
ATCCCGCAAACG





TTCC (510)
TGGA (511)





271
chr7:
chr7:
GCGGGGCGAGGG
GCGGGGCGAGGG
1
59
4.91
8.04E−09
3′ss
CLL



102074108-102076648
102074108-102076671
CAGCTCCGCGTT
CAGCTCCGGGAA





TCTCTGAATTCT
GGAACGTCCCAG





CCCC (512)
GGAT (513)





272
chr1:
chr1:
TCTTTGGAAAAT
TCTTTGGAAAAT
0
29
4.91
3.49E−03
3′ss
CLL



101458310-101460665
101458296-101460665
CTAATCAATTTT
CTAATCAAGGGA





CTGCCTATAGGG
AGGAAGATCTAT





GAAG (25)
GAAC (26)





273
chr7:
chr7:
CCACCTCACCAT
CCACCTCACCAT
0
29
4.91
1.26E−02
3′ss
CLL



99954506-99955849
99954506-99955842
CACCCAGGGCAG
CACCCAGGCCCT





CCCCTCCACAGG
CAGGCAGCCCCT





GCCC (514)
CCAC (515)





274
chr19:
chr19:
GATGGTGGATGA
GATGGTGGATGA
1
57
4.86
7.10E−04
3′ss
CLL



23545541-23556543
23545527-23556543
ACCCACAGTTTT
ACCCACAGGTAT





TTTTTTTCAGGT
ATGTCCTCATTT





ATAT (11)
TCCT (12)





275
chr3:
chr3:
GCCAACCTAGAG
GCCAACCTAGAG
1
56
4.83
2.18E−05
3′ss
CLL



108403188-108405274
108403188-108405291
CCCCCCTGCTCT
CCCCCCTGATGA





CTGCCTCTTACA
CTGGCATAGCCT





GATG (516)
GGGC (517)





276
chr17:
chr17:
GGAGCAGTGCAG
GGAGCAGTGCAG
0
27
4.81
1.14E−04
3′ss
CLL



71198039-71199162
71198039-71199138
TTGTGAAATCAT
TTGTGAAAGTTT





TACTTCTAGATG
TGATTCATGGAT





ATGC (31)
TCAC (32)





277
chr6:
chr6:
AACCGGGGGAGC
AACCGGGGGAGC
0
27
4.81
8.95E−03
3′ss
CLL



41040823-41046743
41040823-41046767
GAGGCACGTTTC
GAGGCACGGAGT





TTTCCCCACCTT
GTACCTCACAGC





TCTA (518)
CTTC (519)





278
chr11:
chr11:
CACACAGACTGC
CACACAGACTGC
1
54
4.78
3.38E−06
3′ss
CLL



62376298-62376433
62376277-62376433
GTTCGATGAGTG
GTTCGATGCCTT





TCTTCCCCCTGC
GCTGTTCACCCT





CTTA (520)
GATG (521)





279
chr14:
chr14:
AGTTAGAATCCA
AGTTAGAATCCA
0
26
4.75
9.14E−07
3′ss
CLL



74358911-74360478
74358911-74360499
AACCAGAGTGTT
AACCAGAGCTCC





GTCTTTTCTCCC
TGGTACAGTTTG





CCCA (61)
TTCA (62)





280
chr11:
chr11:
CATAAAATTCTA
CATAAAATTCTA
2
79
4.74
1.89E−06
3′ss
CLL



4104212-4104471
4104212-4104492
ACAGCTAATTCT
ACAGCTAAGCAA





CTTTCCTCTGTC
GCACTGAGCGAG





TTCA (69)
GTGA (70)





281
chr17:
chr17:
AGACCTACCAGA
AGACCTACCAGA
0
25
4.70
1.18E−02
3′ss
CLL



62574712-62576906
62574694-62576906
AGGCTATGTGTT
AGGCTATGAACA





TATTAATTTTAC
GAGGACAACGCA





AGAA (39)
ACAA (40)





282
chr7:
chr7:
GTTTTTACCTCT
GTTTTTACCTCT
1
49
4.64
1.80E−08
3′ss
CLL



76943820-76950041
76943806-76950041
GCCTCCTGATCT
GCCTCCTGGTTT





CTCATCCTAGGT
TCATACTCTGCA





TTTC (522)
CACC (523)





283
chr20:
chr20:
AGAACTGCACCT
AGAACTGCACCT
0
24
4.64
3.30E−05
3′ss
CLL



62701988-62703210
62701988-62703222
ACACACAGCCCT
ACACACAGGTGC





GTTCACAGGTGC
AGACCCGCAGCT





AGAC (29)
CTGA (30)





284
chr3:
chr3:
CACTGCTGGGAG
CACTGCTGGGAG
0
24
4.64
1.42E−07
3′ss
CLL



129284872-129285369
129284860-129285369
AGTGGAAGTTGC
AGTGGAAGATTC





TTCCACAGATTC
CTGAGAGCTGCC





CTGA (524)
GGCC (525)





285
chr11:
chr11:
GATTTTGGAGAG
GATTTTGGAGAG
0
23
4.58
1.27E−04
3′ss
CLL



33080641-33083060
33080641-33083075
GCAACCAACTTT
GCAACCAAATTC





GTTTTTCACAGA
CCTGGACTTTGT





TTCC (526)
CACC (527)





286
chr1:
chr1:
TCACTCAAACAG
TCACTCAAACAG
0
23
4.58
1.48E−03
3′ss
CLL



179835004-179846373
179834989-179846373
TAAACGAGTTTT
TAAACGAGGTAT





ATCATTTACAGG
GTGACGCATTCC





TATG (53)
CAGA (54)





287
chr2:
chr2:
TGCAGAACTGGA
TGCAGAACTGGA
0
23
4.58
2.35E−02
3′ss
CLL



23977668-23980287
23977644-23980287
TAAAGAAGTGTA
TAAAGAAGGTGC





TTTTTTTGTCTC
TTCTAAAGTAAA





AATT (528)
GAAA (529)





288
chr5:
chr5:
ACTCTTATGCAG
ACTCTTATGCAG
0
23
4.58
4.37E−03
3′ss
CLL



1579622-1585098
1581810-1585098
TCCCCATGAGGT
TCCCCATGAGGA





TATGCTTATGTT
GATCCTAGTCTC





TCTC (530)
ACCA (531)





289
chr6:
chr6:
AGTGTTTTACCA
AGTGTTTTACCA
0
23
4.58
2.41E−04
3′ss
CLL



30884736-30884871
30884736-30884881
TGGATGTTGTCA
TGGATGTTGGCT





TTCCAGGGCTCC
CCTCAGTGGCTG





TCAG (532)
TGAC (533)





290
chr6:
chr6:
TTTATGATGCTG
TTTATGATGCTG
0
23
4.58
1.66E−02
3′ss
CLL



49416664-49419178
49416640-49419178
CTTTAAAGTTTT
CTTTAAAGCTCA





GTTAATGTTTTT
TTAATGAAATTG





CTTT (534)
AAGA (535)





291
chr8:
chr8:
ATCTAAAAACAG
ATCTAAAAACAG
0
23
4.58
3.15E−03
3′ss
CLL



61741365-61742868
61741365-61742880
AAGAGCAGGTCC
AAGAGCAGGTGC





TTTTTTAGGTGC
AAAAACTTCAAG





AAAA (536)
CTAT (537)





292
chr2:
chr2:
AGCAAGTAGAAG
AGCAAGTAGAAG
2
68
4.52
3.76E−08
3′ss
CLL



109102364-109102954
109102364-109102966
TCTATAAAATTT
TCTATAAAATAC





ACCCCCAGATAC
AGCTGGCTGAAA





AGCT (1)
TAAC (2)





293
chr15:
chr15:
GGATTGCAGCCA
GGATTGCAGCCA
0
22
4.52
5.30E−05
3′ss
CLL



72859518-72862504
72859518-72862517
ACACAAAGTTTC
ACACAAAGGAAT





TCTTCATAGGAA
GTCCCAAATGCC





TGTC (538)
ATGT (539)





294
chr5:
chr5:
GGTTTCGAGTTT
GGTTTCGAGTTT
0
22
4.52
1.57E−02
3′ss
CLL



109181707-109183328
109181707-109183357
GAATAGTGTTTT
GAATAGTGGTCA





GCTTGTTTGTTT
GATTGAAGTTAT





GTTT (540)
CATG (541)





295
chr9:
chr9:
AAATGAAGAAAC
AAATGAAGAAAC
0
22
4.52
5.36E−04
3′ss
CLL



125759640-125760854
125759640-125760875
TCCTAAAGCCTC
TCCTAAAGATAA





TCTCTTTCTTTG
AGTCCTGTTTAT





TTTA (67)
GACC (68)





296
chr11:
chr11:
GGATGACCGGGA
GGATGACCGGGA
2
65
4.46
7.66E−06
3′ss
CLL



71939542-71939690
71939542-71939770
TGCCTCAGTCAC
TGCCTCAGATGG





TTTACAGCTGCA
GGAGGATGAGAA





TCGT (47)
GCCC (48)





297
chr11:
chr11:
CCACCGCCATCG
CCACCGCCATCG
2
65
4.46
2.31E−08
3′ss
CLL



64877395-64877934
64877395-64877953
ACGTGCAGTACC
ACGTGCAGGTGG





TCTTTTTACCAC
GGCTCCTGTACG





CAGG (167)
AAGA (168)





298
chr19:
chr19:
TGCCTGTGGACA
TGCCTGTGGACA
0
21
4.46
1.50E−04
3′ss
CLL



14031735-14034130
14031735-14034145
TCACCAAGCCTC
TCACCAAGGTGC





GTCCTCCCCAGG
CGCCTGCCCCTG





TGCC (59)
TCAA (60)





299
chr11:
chr11:
CGCAAGTACTTC
CGCAAGTACTTC
0
20
4.39
2.24E−03
3′ss
CLL



64676597-64676742
64676622-64676742
CTGCCCCATCCA
CTGCCCCAGGTA





GCAGCACACAGT
GTGGTGACTGTG





GGGA (542)
AACC (543)





300
chr22:
chr22:
TTCATAACAAAC
TCATCAATGCCC
0
20
4.39
1.08E−04
5′ss
CLL



24210086-24210667
24204389-24210667
CAGTAAATCACA
CGACCTTGCACA





TTCAGGAATTCA
TTCAGGAATTCA





CCAA (544)
CCAA (545)





301
chr2:
chr2:
AAATTTAACATT
AAATTTAACATT
0
20
4.39
2.96E−02
3′ss
CLL



24207701-24222524
24207701-24222541
ACTCATAGTTTT
ACTCATAGAGTA





TGCTGTTTTACA
AGCCATATCAAA





GAGT (546)
GACT (547)





302
chr11:
chr11:
CACCGGGAGCTG
CACCGGGAGCTG
2
59
4.32
8.17E−07
3′ss
CLL



64119858-64120198
64119858-64120215
CAGGGCCGCCCC
CAGGGCCGGCAC





TTGTCCATCCCA
GAGCAGCTGCAG





GGCA (548)
GCCC (549)





303
chr11:
chr11:
GGAGGTGGACCT
GGAGGTGGACCT
0
19
4.32
5.52E−04
3′ss
CLL



68363686-68367788
68363686-68367808
GAGTGAACAATT
GAGTGAACCACC





TCTCCCCTCTTT
CAACTGGTCAGC





TTAG (189)
TAAC (190)





304
chr11:
chr11:
ATTGGACACAGA
CTGTCTCTAGGC
0
19
4.32
5.03E−04
5′ss
CLL



984190-984644
981299-984644
GATGGGATATCG
TAAGCAGAATCG





TGACGTCTGCAT
TGACGTCTGCAT





CCAC (550)
CCAC (551)





305
chr17:
chr17:
GGGACCTCACCA
GGGACCTCACCA
0
19
4.32
5.14E−03
3′ss
CLL



43522984-43527983
43523029-43527983
AGCGCCCGCCCC
AGCGCCCGATCT





TCATCAACCTGC
GCAGGCAGGCCC





AGAT (552)
TGAA (553)





306
chr9:
chr9:
CCAAGGACTGCA
CCAAGGACTGCA
2
57
4.27
1.96E−04
3′ss
CLL



139837449-139837800
139837395-139837800
CTGTGAAGGCCC
CTGTGAAGATCT





CCGCCCCGCGAC
GGAGCAACGACC





CTGG (175)
TGAC (176)





307
chr4:
chr4:
GAGTGTGAATCA
GAGTGTGAATCA
2
56
4.25
3.01E−02
3′ss
CLL



56874548-56875878
56874548-56875900
TCTGTGAATTTC
TCTGTGAACCAG





ACATCACTCATT
CTGAAAGAAACA





TAAC (554)
TTGG (555)





308
chr5:
chr5:
AGCATTGCTAGA
AGCATTGCTAGA
1
37
4.25
3.83E−05
3′ss
CLL



139815842-139818078
139815842-139818045
AGCAGCAGCTTT
AGCAGCAGGAAT





TGCAGATCCTGA
TGGCAAATTGTC





GGTA (19)
AACT (20)





309
chr22:
chr22:
TCATCAATGCCC
TCATCAATGCCC
0
18
4.25
3.60E−04
3′ss
CLL



24204389-24209938
24204389-24210667
CGACCTTGGTTC
CGACCTTGCACA





ATGAACACATTG
TTCAGGAATTCA





AGGT (556)
CCAA (545)





310
chr3:
chr3:
GCATTTCTGAGA
GCATTTCTGAGA
0
18
4.25
3.30E−03
3′ss
CLL



38038678-38038959
38038678-38038973
AGGCTCGGGTCC
AGGCTCGGGGGC





TCTCCCGCAGGG
TGGCTTTGACCT





GCTG (557)
ACAG (558)





311
chr6:
chr6:
GCCAGTCCAGAG
GCCAGTCCAGAG
1
36
4.21
6.38E−07
3′ss
CLL



109767078-109767338
109767065-109767338
CCCTCAAGTTCT
CCCTCAAGCTCT





TCTTCTCAGCTC
TGTGGCCATGGA





TTGT (559)
GAAG (560)





312
chr1:
chr1:
TGGCCGAGGCGC
TGGCCGAGGCGC
2
54
4.20
1.35E−04
3′ss
CLL



16803042-16803424
16802999-16803424
TGACCAAGACCT
TGACCAAGGCTG





TACTCAGGGGAT
AGGGCAGAGGAG





CCTC (561)
GCCT (562)





313
chr2:
chr2:
TCTACTTGGTGG
TCTACTTGGTGG
3
72
4.19
1.68E−06
3′ss
CLL



103348885-103353104
103348868-103353104
GCTTCTTGCATT
GCTTCTTGGATT





TATTTTGTTTTA
TGTTTGGTGTCA





GGAT (563)
GCAT (564)





314
chr14:
chr14:
GCTCCTGCTCAG
GCTCCTGCTCAG
0
17
4.17
3.99E−04
3′ss
CLL



78203438-78205120
78203418-78205120
TATATCCGTTTT
TATATCCGATAC





TATCTGCTTTCT
ACACCATCTCAG





TCAG (565)
CAAG (566)





315
chr3:
chr3:
GAAATAGGGCAC
GAAATAGGGCAC
0
17
4.17
7.71E−03
3′ss
CLL



122152652-122156016
122152635-122156016
AGATCCAGTTTT
AGATCCAGACTG





TCTTTAATTTTA
TGATAGATGCCA





GACT (567)
ACAT (568)





316
chr18:
chr18:
GCAACCTGTGTT
GCAACCTGTGTT
1
33
4.09
3.11E−03
3′ss
CLL



33724997-33725896
33724997-33725910
TTACAAAGGTTT
TTACAAAGATGG





TATTTTTTAGAT
TGTCCTACAGCA





GGTG (569)
GCCA (570)





317
chr7:
chr7:
GTATCAAAGTGT
GTATCAAAGTGT
1
33
4.09
4.37E−04
3′ss
CLL



94157562-94162500
94157562-94162516
GGACTGAGATTT
GGACTGAGGATT





GTCTTCCTTTAG
CCATTGCAAAGC





GATT (27)
CACA (28)





318
chr4:
chr4:
CCCCTGAAGTAC
CCCCTGAAGTAC
0
16
4.09
1.12E−04
3′ss
CLL



39868635-39871013
39868617-39871013
TAGCAAAGCATG
TAGCAAAGGTAC





TTAATATTTTAT
AGGCAATTAAAC





AGGT (571)
TTCT (572)





319
chr10:
chr10:
GTTCCTCACTTT
GTTCCTCACTTT
1
31
4.00
1.17E−04
3′ss
CLL



99502921-99504468
99502921-99504485
GAATGAGGTGTT
GAATGAGGGTGC





TTTGATTCTGCA
ATGGTACTCAGT





GGTG (573)
AGGT (574)





320
chr1:
chr1:
TCAGCCCTCTGA
TCAGCCCTCTGA
0
15
4.00
6.99E−03
3′ss
CLL



226036315-226036597
226036255-226036597
ACTACAAAGGTG
ACTACAAAACAG





TTTGTTCACAGA
AAGAGCCTGCAA





GATC (93)
GTGA (94)





321
chr20:
chr20:
TCTTGGAAGGCA
TCTTGGAAGGCA
0
15
4.00
4.25E−03
3′ss
CLL



31983014-31984566
31982922-31984566
GAGAAAAGATAT
GAGAAAAGTCTA





TTCTAGAGCATT
CCTCGAGACCTA





TGGG (575)
TGGC (576)





322
chr2:
chr2:
AACCCGGAGAGA
AACCCGGAGAGA
0
15
4.00
5.64E−03
3′ss
CLL



64456774-64456978
64456774-64478252
AAAGGGAGTTTG
AAAGGGAGCAAC





TTTTTAGGTCAG
TGATGTTGCCAT





AGTC (577)
GCAG (578)





323
chr11:
chr11:
AATCTTCCCCAA
AATCTTCCCCAA
1
30
3.95
7.37E−04
3′ss
CLL



92887382-92895871
92887443-92895871
GATGTATGTTCT
GATGTATGGTTA





ATGTTCCAGCAG
TATCAATCAGTG





AGAT (579)
AAAA (580)





324
chr18:
chr18:
CTCTCTTGTCAG
CTCTCTTGTCAG
1
30
3.95
2.23E−02
3′ss
CLL



43459192-43460039
43459179-43460039
ACAAGCAGTTGT
ACAAGCAGGTAA





CTCTTCCAGGTA
TGGAGACTATAC





ATGG (581)
AGTG (582)





325
chr5:
chr5:
GCAGAGCTGTGG
GCAGAGCTGTGG
1
30
3.95
1.23E−03
3′ss
CLL



138724290-138725368
138724274-138725368
CTTACCAGTCCC
CTTACCAGATGT





TCCTTGTTCCAG
GGCAAAATCTGG





ATGT (583)
CAAA (584)





326
chr17:
chr17:
TGCAGGAGACCG
TGCAGGAGACCG
1
29
3.91
7.83E−03
3′ss
CLL



58163509-58165557
58163487-58165557
GCTTTTGGGTCC
GCTTTTGGATAC





CCTTCTTATACC
TGCTAATCAGTC





CCTC (585)
CTAG (586)





327
chr1:
chr1:
AGTTACAACGAA
AGTTACAACGAA
1
29
3.91
2.95E−05
3′ss
CLL



185056772-185060696
185056772-185060710
CACCTCAGTGAC
CACCTCAGGAGG





TCTTTTACAGGA
CAATAACAGATG





GGCA (162)
GCTT (163)





328
chr10:
chr10:
TCTTGCCAGAGC
TCTTGCCAGAGC
0
14
3.91
5.04E−05
3′ss
CLL



99219232-99219415
99219283-99219415
TGCCCACGCTCT
TGCCCACGCTTC





CCACCCTCAGCT
TTTCCTTGCTGC





GCCT (587)
TGGA (588)





329
chr4:
chr4:
CCATGGTCAAAA
CCATGGTCAAAA
0
14
3.91
4.36E−02
3′ss
CLL



152022314-152024139
152022314-152024022
AATGGCAGCACC
AATGGCAGACAA





AACAGGTCCGCC
TGATTGAAGCTC





AAAT (344)
ACGT (345)





330
chr1:
chr1:
ATCAGAAATTCG
ATCAGAAATTCG
3
57
3.86
4.89E−06
3′ss
CLL



212515622-212519131
212515622-212519144
TACAACAGGTTT
TACAACAGCTCC





CTTTTAAAGCTC
TGGAGCTTTTTG





CTGG (65)
ATAG (66)





331
chr1:
chr1:
GCAGGCTGCCCG
GCAGGCTGCCCG
4
69
3.81
2.04E−07
3′ss
CLL



156552962-156553113
156552962-156553129
GGACTCTGGCTC
GGACTCTGGGGA





TCTTTCTCTCAG
CATGAAGGGACA





GGGA (589)
GTGG (590)





332
chr6:
chr6:
GCCAGTCCAGAG
GCCAGTCCAGAG
2
41
3.81
4.40E−03
3′ss
CLL



109767165-109767338
109767065-109767338
CCCTCAAGTCTT
CCCTCAAGCTCT





TACCAGACTTGC
TGTGGCCATGGA





AGGG (591)
GAAG (560)





333
chr20:
chr20:
ACATGAAGGTGG
ACATGAAGGTGG
5
81
3.77
1.48E−08
3′ss
CLL



34144042-34144725
34144042-34144743
ACGGAGAGGCTC
ACGGAGAGGTAC





CCCTCCCACCCC
TGAGGACAAATC





AGGT (49)
AGTT (50)





334
chr17:
chr17:
CTATTTCACTCT
CTATTTCACTCT
1
25
3.70
2.79E−05
3′ss
CLL



7131030-7131295
7131102-7131295
CCCCCGAACCTA
CCCCCGAAATGA





TCCAGGTTCCTC
GCCCATCCAGCC





CTCC (33)
AATT (34)





335
chr6:
chr6:
TTCCCACTGGTC
TTCCCACTGGTC
1
25
3.70
3.91E−03
3′ss
CLL



110085185-110086201
110085185-110086215
GCCTGCAGGTAT
GCCTGCAGACTG





TTCTCTTTAGAC
GCATCCTTCGAA





TGGC (592)
CCAA (593)





336
chr7:
chr7:
TGTAAATGGGGA
TGTAAATGGGGA
1
25
3.70
2.18E−05
3′ss
CLL



889240-889468
889240-889559
AGCGCTGTTTTC
AGCGCTGTGCGA





TACAGACTGCCA
CGACTGTAAGGG





TTGC (594)
CAAG (595)





337
chr12:
chr12:
TCAATGCAAATA
TCAATGCAAATA
0
12
3.70
1.92E−03
3′ss
CLL



112915534-112915638
112915534-112915660
TCATCATGGATT
TCATCATGCCTG





TTCTTCCTAAAT
AATTTGAAACCA





TTCT (596)
AGTG (597)





338
chr14:
chr14:
ACAAATCAACTG
ACAAATCAACTG
0
12
3.70
1.38E−03
3′ss
CLL



56100059-56101230
56100059-56101243
GAAAGCAATTAC
GAAAGCAAGCAG





TGTTTTCAGGCA
TCTGCAGAACTA





GTCT (598)
AATA (599)





339
chr17:
chr17:
CAAAGCGCCCAG
CAAAGCGCCCAG
0
12
3.70
2.10E−02
3′ss
CLL



2266428-2266727
2266428-2266758
CCCTGGGGGCTG
CCCTGGGGATCC





GAGGCTGAGCCC
GGAAACGGCACT





CGGC (600)
CAAG (601)





340
chr19:
chr19:
TGACACAGCCCT
TGACACAGCCCT
0
12
3.70
4.53E−05
3′ss
CLL



16264018-16265158
16264018-16265208
GCAGGCAGGACC
GCAGGCAGAAGG





TTTCCCCCTCCC
ATCCCGCAAACG





TAGT (602)
TGGA (511)





341
chr1:
chr1:
AGTTGCCATTCC
AGTTGCCATTCC
0
12
3.70
4.52E−03
3′ss
CLL



186324917-186325417
186324900-186325417
ATTACATGTCTT
ATTACATGCTTC





TACTTTCCTGAA
AAGCTTAGATGA





GCTT (603)
TGTT (604)





342
chr3:
chr3:
ACTGATTAAAAA
ACTGATTAAAAA
4
62
3.66
9.33E−05
3′ss
CLL



56649300-56649931
56649300-56649949
TCTTGGTGGTGA
TCTTGGTGTTGA





TTTCTCTTTGCC
TACAATACAAAT





AGTT (605)
GGAA (606)





343
chr6:
chr6:
CCGGGGCCTTCG
CCGGGGCCTTCG
4
58
3.56
3.53E−06
3′ss
CLL



10723474-10724788
10723474-10724802
TGAGACCGCTTG
TGAGACCGGTGC





TTTTCTGCAGGT
AGGCCTGGGGTA





GCAG (95)
GTCT (96)





344
chr3:
chr3:
AGGCTATTGTTG
AGGCTATTGTTG
1
22
3.52
2.36E−03
3′ss
CLL



184587316-184588487
184587316-184588503
CAGACCGGGCTG
CAGACCGGATGG





TTTTCCTTACAG
TAGAAATCCTAT





ATGG (607)
TCCA (608)





345
chr4:
chr4:
CCTTTCAAGAAA
CCTTTCAAGAAA
1
22
3.52
1.60E−02
3′ss
CLL



3124663-3125976
3124663-3127275
ACAAAAAGTCGC
ACAAAAAGGCAA





TTTTTCCAGTGG
AGTGCTCTTAGG





CGGT (609)
AGAA (610)





346
chr9:
chr9:
ACACGGAGCTCA
ACACGGAGCTCA
2
33
3.50
1.45E−05
3′ss
CLL



123933826-123935634
123933826-123935520
AGAAACAGTTTC
AGAAACAGATGG





TTCCAGAACTAC
CAAACCAAAAAG





CAGC (611)
ATTT (612)





347
chr19:
chr19:
CAAGCAGGTCCA
CAAGCAGGTCCA
6
76
3.46
9.28E−05
3′ss
CLL



5595521-5598803
5595508-5598803
AAGAGAGATTTT
AAGAGAGAAGCT





GGTAAACAGAGC
CCAAGAGTCAGG





TCCA (138)
ATCG (139)





348
chr5:
chr5:
GACTTCGAACAT
GACTTCGAACAT
4
54
3.46
7.66E−03
3′ss
CLL



78608321-78610192
78608321-78610079
TTAAACAGTGTG
TTAAACAGAGGT





TTACAGGTAGAA
ATCCTGGGCAAG





GAGA (613)
TCAT (614)





349
chr2:
chr2:
ACCACGAAGGGT
ACCACGAAGGGT
2
32
3.46
1.25E−02
3′ss
CLL



231050873-231065600
231050859-231065600
CACACAAGTCTA
CACACAAGGGGC





TTTGGTCCAGGG
AGCCTCACCTGG





GCAG (615)
GCAT (616)





350
chr1:
chr1:
CGATCTCCCAAA
CGATCTCCCAAA
1
21
3.46
1.57E−05
3′ss
CLL



52880319-52880412
52880319-52880433
AGGAGAAGTCTG
AGGAGAAGCCCC





ACCAGTCTTTTC
TCCCCTCGCCGA





TACA (55)
GAAA (56)





351
chr2:
chr2:
TTAACAAACACG
TGCTGGCACACC
0
10
3.46
8.22E−03
5′ss
CLL



69015785-69034404
69015088-69034404
TGAATCTACAGT
CTGTGGAGCAGT





GTTTGGCCAGCG
GTTTGGCCAGCG





CTTG (617)
CTTG (618)





352
chr5:
chr5:
CGCCCCAGGGCA
CGCCCCAGGGCA
0
10
3.46
1.97E−03
3′ss
CLL



156915521-156916109
156915497-156916109
AGCGAAAGGTGT
AGCGAAAGGTGA





TCCTTGACTTGT
TCAACACTCCGG





GCGT (619)
AAAT (620)





353
chr9:
chr9:
TGGTACAACTTC
TGGTACAACTTC
0
10
3.46
6.70E−03
3′ss
CLL



115934002-115935732
115933986-115935732
AGGAAAAGTCTG
AGGAAAAGTGTT





TTTGTTTTGCAG
TAGCCCTCCAGG





TGTT (621)
CCCA (622)





354
chr14:
chr14:
TGGATTTGCTCG
TGGATTTGCTCG
1
20
3.39
1.52E−04
3′ss
CLL



50808004-50808849
50807950-50808849
GCTTTTGATTTT
GCTTTTGACTGG





GATTCCAGCCTT
ACCGAGTGACTA





CCGC (623)
CTAT (624)





355
chr18:
chr18:
GATGAGGACCCC
GATGAGGACCCC
5
61
3.37
3.06E−06
3′ss
CLL



9133520-9136361
9133508-9136361
CACATAGGTTTC
CACATAGGGATG





CAAACCAGGATG
GCCATAGCAGCC





GCCA (625)
ACAA (626)





356
chr10:
chr10:
TACCTCTGGTTC
TACCTCTGGTTC
3
39
3.32
2.21E−05
3′ss
CLL



99214556-99215395
99214556-99215416
CTGTGCAGTCTT
CTGTGCAGTTCT





CGCCCCTCTTTT
GTGGCACTTGCC





CTTA (13)
CTGG (14)





357
chr2:
chr2:
TGTTTTAAATTC
TGTTTTAAATTC
2
29
3.32
8.44E−06
3′ss
CLL



225670231-225670842
225670246-225670842
CATAGCAGCTAT
CATAGCAGCATT





TTCTACAGTAAA
TTCATCAATAGC





CCAT (627)
TATT (628)





358
chrX:
chrX:
GCTGGGATGTTA
GCTGGGATGTTA
1
19
3.32
2.06E−02
3′ss
CLL



153323986-153357641
153298008-153357641
GGGCTCAGCCTG
GGGCTCAGGGAA





TCGTTCCAGGAC
GAAAAGTCAGAA





CCAG (629)
GACC (630)





359
chr16:
chr16:
CTGGTTATTGCA
CTGGTTATTGCA
0
9
3.32
6.10E−05
3′ss
CLL



72139523-72139882
72139523-72139903
AATTAAAGCTCT
AATTAAAGGTCT





TTGCCGTCCCCT
TCAACCCCAGGA





CCTA (631)
TTGG (632)





360
chr5:
chr5:
CTCCATGCTCAG
CTCCATGCTCAG
4
48
3.29
1.01E−06
exon
CLL



869519-870587
865696-870587
CTCTCTGGTTTC
CTCTCTGGGGAA




incl.





TTTCAGGGCCTG
GGTGAAGAAGGA





CCAT (128)
GCTG (129)





361
chrX:
chrX:
GGTCATGCTAAT
GGTCATGCTAAT
8
82
3.21
5.22E−07
3′ss
CLL



70516897-70517210
70516897-70517226
GAGACAGGTCTG
GAGACAGGATTT





TTGTTTTTTTAG
GATGAGGCGCCA





ATTT (633)
AGAA (634)





362
chr16:
chr16:
GTCAGCATTTGC
GTCAGCATTTGC
2
26
3.17
7.43E−04
3′ss
CLL



47347747-47399698
47347734-47399698
AGACTTTGTTTC
AGACTTTGATGG





TTTTGGCAGATG
AGATGGACACAT





GAGA (635)
GGAT (636)





363
chr5:
chr5:
GCAGAGCTGTGG
GCAGAGCTGTGG
2
26
3.17
1.17E−03
3′ss
CLL



138725125-138725368
138724274-138725368
CTTACCAGACTT
CTTACCAGATGT





CTCCCTTTCCAG
GGCAAAATCTGG





GCCC (637)
CAAA (584)





364
chr11:
chr11:
CGGCGCGGGCAA
CGGCGCGGGCAA
0
8
3.17
6.70E−03
3′ss
CLL



62648919-62649352
62648919-62649364
CCTGGCGGCCCC
CCTGGCGGGTCT





CATTTCAGGTCT
GAAGGGGCGTCT





GAAG (165)
CGAT (166)





365
chr11:
chr11:
TGCAGCTGGCCC
TGCAGCTGGCCC
0
8
3.17
2.22E−02
3′ss
CLL



64002365-64002911
64002365-64002929
CCGCCCAGGTCT
CCGCCCAGGCCC





TTTCTCTCCCAC
CTGTCTCCCAGC





AGGC (638)
CTGA (639)





366
chr14:
chr14:
CACAGCAAGCAC
CACAGCAAGCAC
0
8
3.17
3.01E−05
3′ss
CLL



31169464-31171484
31169464-31171501
CTTCTGAGTTCT
CTTCTGAGGCTG





TTTCTTATTTCA
ATTTGGAGCAAT





GGCT (640)
ATAA (641)





367
chr1:
chr1:
TCACACCTGTAG
TCACACCTGTAG
0
8
3.17
9.33E−05
3′ss
CLL



186300728-186301326
186300713-186301326
GAACTGAGTGTA
GAACTGAGGAAG





TTATGATACAGG
AAGTTATGGCAG





AAGA (642)
AAGA (643)





368
chr5:
chr5:
AAAATTGACTAT
AAAATTGACTAT
0
8
3.17
7.30E−03
3′ss
CLL



169101449-169108733
169101449-169108747
GGCAACAATTTT
GGCAACAAAATC





TGCTTTACAGAA
CTTGAGCTTGAT





TCCT (644)
TTGA (645)





369
chr9:
chr9:
ACACGGAGCTCA
ACACGGAGCTCA
0
8
3.17
5.42E−04
3′ss
CLL



123933826-123935644
123933826-123935520
AGAAACAGAACT
AGAAACAGATGG





ACCAGCAGATCT
CAAACCAAAAAG





AGAA (646)
ATTT (612)





370
chr10:
chr10:
GGGAGGAAAAGT
GGGAGGAAAAGT
5
52
3.14
1.27E−03
3′ss
CLL



112058568-112060304
112058548-112060304
AATTAATGTTTT
AATTAATGGAAG





TGTTTTTCTTTT
TTATAGAACTAA





TTAG (647)
CCAA (648)





371
chr3:
chr3:
ATTTGGATCCTG
ATTTGGATCCTG
4
43
3.14
1.46E−04
3′ss
CLL



196792335-196792578
196792319-196792578
TGTTCCTCTTTT
TGTTCCTCATAC





TTTCTGTTAAAG
AACTAGACCAAA





ATAC (87)
ACGA (88)





372
chr12:
chr12:
ATTTGGACTCGC
ATTTGGACTCGC
3
34
3.13
1.20E−04
3′ss
CLL



105601825-105601935
105601807-105601935
TAGCAATGATGT
TAGCAATGAGCA





CTGTTTATTTTT
TGACCTCTCAAT





AGAG (41)
GGCA (42)





373
chr19:
chr19:
CTATGGGCTCAC
CTATGGGCTCAC
7
67
3.09
2.90E−04
3′ss
CLL



41084118-41084353
41084118-41084367
TCCTCTGGTCCT
TCCTCTGGTTCG





CCTGTTGCAGTT
TCGCCTGCAGCT





CGTC (169)
TCGA (170)





374
chr11:
chr11:
TTCTCCAGGACC
TTCTCCAGGACC
1
16
3.09
4.69E−03
3′ss
CLL



125442465-125445146
125442465-125445158
TTGCCAGACCTT
TTGCCAGAGGAA





TTCTATAGGGAA
TCAAAGACTCCA





TCAA (150)
TCTG (151)





375
chr12:
chr12:
AGAAGGAGCTGC
AGAAGGAGCTGC
1
16
3.09
2.88E−03
3′ss
CLL



110437589-110449795
110437589-110449809
AGGGCCAGTGTT
AGGGCCAGAATG





TCCTTCACAGAA
TGGAGGCTGTGG





TGTG (649)
ACCC (650)





376
chr8:
chr8:
GCTCTGGAGAAT
GCTCTGGAGAAT
4
41
3.07
6.90E−07
3′ss
CLL



126051218-126052036
126051201-126052036
CTCAATAAGGTT
CTCAATAAGGCT





TTTCTTCCTTTA
CTCCTAGCAGAC





GGGC (651)
ATTG (652)





377
chr3:
chr3:
CATGCAATGAAC
CATGCAATGAAC
2
24
3.06
7.00E−06
3′ss
CLL



42674315-42675109
42674315-42675071
CCAAAAGGTTGA
CCAAAAGGTCAC





TTCCAGTGCTAA
TCTGAGAGGAGT





AAGG (653)
GATA (654)





378
chr5:
chr5:
TGCTTCCGGAAC
TGCTTCCGGAAC
6
57
3.05
3.26E−05
3′ss
CLL



139941307-139941428
139941286-139941428
AGTGACAGCCCC
AGTGACAGGGAC





ATCTCTGCCCCT
TTCGCTTTTGTG





GCTA (655)
GCAA (656)





379
chr12:
chr12:
TGGGTTTCAGCA
TGGGTTTCAGCA
0
7
3.00
4.31E−03
3′ss
CLL



64199184-64202434
64199184-64202454
AGAGAACATTGT
AGAGAACACTGG





TTTTCTGATTTT
CAGCCTCAGGAA





CTAG (657)
ACAA (658)





380
chr18:
chr18:
AGGACATGGATT
AGGACATGGATT
0
7
3.00
4.13E−03
3′ss
CLL



47311742-47313660
47311721-47313660
TGGTAGAGTGCT
TGGTAGAGGTGA





CTAATTTTTGTT
ATGAAGCTTTTG





TTAA (659)
CTCC (660)





381
chr19:
chr19:
ATCACAACCGGA
ATCACAACCGGA
0
7
3.00
2.46E−02
3′ss
CLL



15491444-15507960
15491423-15507960
ACCGCAGGCTCC
ACCGCAGGCTCA





TTCTGCCCTGCC
TGATGGAGCAGT





CGCA (661)
CCAA (662)





382
chr1:
chr1:
CAGGAAGCAGCT
CAGGAAGCAGCT
0
7
3.00
7.09E−04
3′ss
CLL



46068037-46070588
46068037-46070607
AGTCTTTTATGT
AGTCTTTTAGGT





TTATTCTCTTTG
AAGAAGTATGGA





TAGA (663)
GAGA (664)





383
chr21:
chr21:
GAACCAATGGAA
GAACCAATGGAA
0
7
3.00
1.40E−02
3′ss
CLL



45452053-45452682
45452053-45457672
TGGAGAAGGCAC
TGGAGAAGGTCC





AGGCGTTTTGCA
TATGGCCGGGCT





AAGG (665)
CCGA (666)





384
chr2:
chr2:
TGCTTGTAAAAT
TGCTTGTAAAAT
0
7
3.00
1.13E−02
3′ss
CLL



160673561-160676236
160673543-160676236
TGAAATGGTGCT
TGAAATGGTTGA





TTTAATTATTAT
CTACAAAGAAGA





AGTT (667)
ATAT (668)





385
chr5:
chr5:
ACTCGCGCCTCT
ACTCGCGCCTCT
0
7
3.00
4.59E−02
3′ss
CLL



150411955-150413168
150411944-150413168
TCCATCTGTTTT
TCCATCTGCCGG





GTCGCAGCCGGA
AATACACCTGGC





ATAC (109)
GTCT (110)





386
chr7:
chr7:
CCACCTCACCAT
CCACCTCACCAT
0
7
3.00
2.08E−02
3′ss
CLL



99954506-99955853
99954506-99955842
CACCCAGGCCCC
CACCCAGGCCCT





TCCACAGGGCCC
CAGGCAGCCCCT





CTCT (669)
CCAC (515)





387
chr4:
chr4:
CGTCTCCATGAC
CGTCTCCATGAC
6
54
2.97
7.33E−05
3′ss
CLL



995351-995438
995351-995466
CATGCAAGGTGT
CATGCAAGGCTT





AGACGCAGTGCT
CCTGAACTACTA





CCCC (670)
CGAT (671)





388
chr15:
chr15:
AGGAGGCAATTA
AGGAGGCAATTA
8
68
2.94
1.81E−04
3′ss
CLL



75131104-75131350
75131086-75131350
AGGCAAAGGCCC
AGGCAAAGGTGG





TTTCCCTGCTAC
GGCAGTACGTGT





AGGT (672)
CCCG (673)





389
chrX:
chrX:
TACAAGAGCTGG
TACAAGAGCTGG
2
22
2.94
1.26E−04
3′ss
CLL



153699660-153699819
153699660-153699830
GTGGAGAGGGTC
GTGGAGAGGTAT





CCAACAGGTATT
TATCGAGACATT





ATCG (158)
GCAA (159)





390
chr9:
chr9:
CACCACGCCGAG
CACCACGCCGAG
5
43
2.87
3.76E−08
3′ss
CLL



125023777-125026993
125023787-125026993
GCCACGAGACAT
GCCACGAGTATT





TGATGGAAGCAG
TCATAGACATTG





AAAC (142)
ATGG (143)





391
chr14:
chr14:
TTACCTCCGAAG
TTACCTCCGAAG
10
79
2.86
3.40E−05
3′ss
CLL



23242937-23243141
23242925-23243141
GATCGTGGTTCT
GATCGTGGGGTC





CTTTGTAGGGTC
TGCCACAAGGTA





TGCC (674)
CCTC (675)





392
chr11:
chr11:
AATAAGCCCTCA
AATAAGCCCTCA
0
6
2.81
1.66E−02
3′ss
CLL



67376193-67376896
67376193-67376922
GATGGCAGCCTG
GATGGCAGGCCC





TCTGACCTGTGG
AAGTATCTGGTG





GCCC (676)
GTGA (677)





393
chr16:
chr16:
ACTCCCAGCTCA
ACTCCCAGCTCA
0
6
2.81
1.49E−02
3′ss
CLL



56403209-56419830
56403239-56419830
ATGCAATGGTTC
ATGCAATGGCTC





CATACCATCTGG
ATCAGATTCAAG





TACT (332)
AGAT (333)





394
chr17:
chr17:
GCCTGGACCTGT
GCCTGGACCTGT
0
6
2.81
4.26E−02
3′ss
CLL



43316432-43317875
43316432-43317842
ACTTGGAGGTGC
ACTTGGAGAGGC





AGATCCAGGCGT
TTCGGCTCACCG





ACCT (678)
AGAG (679)





395
chr21:
chr21:
CTGTAACTACTA
CTGTAACTACTA
0
6
2.81
3.47E−04
3′ss
CLL



47655360-47656742
47655340-47656742
GCCCACAGTTTC
GCCCACAGAGTG





TTTTTTATTCAA
ACATGATGAGGG





ATAG (680)
AGCA (681)





396
chr3:
chr3:
CTCTCAATGCAG
CTCTCAATGCAG
0
6
2.81
1.49E−03
3′ss
CLL



71019345-71019886
71015207-71019886
CTTTACAGTTTT
CTTTACAGGCTT





CCTGCAGATTGT
CAATGGCTGAGA





TCAA (682)
ATAG (683)





397
chr9:
chr9:
GGAGCAGTTCCA
GGAGCAGTTCCA
0
6
2.81
4.44E−03
3′ss
CLL



95007367-95009658
95007353-95009658
GAAGACTGCTGC
GAAGACTGGGAC





TTCTCCATAGGG
CATTGTTGTGGA





ACCA (684)
AGGC (685)





398
chrX:
chrX:
CCTGCTGGACCA
CCTGCTGGACCA
0
6
2.81
1.25E−02
3′ss
CLL



48340103-48340769
48340103-48340796
TTCTTACGTTGT
TTCTTACGATTT





CTCCCCCTGTTC
CAACCAGCTGGA





CTAA (686)
TGGT (687)





399
chr20:
chr20:
GGATTTTGATAA
GGATTTTGATAA
7
53
2.75
1.01E−03
3′ss
CLL



36631195-36634598
36631178-36634598
TGAAGAAGTTGT
TGAAGAAGAGGA





GCTCTTTTTCCA
ACAGTCAGTCCC





GAGG (688)
TCCC (689)





400
chr4:
chr4:
CGTCTCCATGAC
CGTCTCCATGAC
3
26
2.75
5.89E−04
3′ss
CLL



995351-995433
995351-995466
CATGCAAGGGCA
CATGCAAGGCTT





GGTGTAGACGCA
CCTGAACTACTA





GTGC (690)
CGAT (671)





401
chr15:
chr15:
TGATTCCAAGCA
TGATTCCAAGCA
2
19
2.74
3.63E−05
3′ss
CLL



25213229-25219533
25213229-25219457
AAAACCAGCCTT
AAAACCAGGCTC





CCCCTAGGTCTT
CATCTACTCTTT





CAGA (230)
GAAG (231)





402
chr18:
chr18:
AGTGCCAGCTGC
AGTGCCAGCTGC
2
19
2.74
1.04E−03
exon
CLL



47811617-47812118
47811721-47812118
GGGCCCGGCTCT
GGGCCCGGGAAT




skip





CACCAGTGACGC
CGTACAAGTACT





CCTC (691)
TCCC (692)





403
chr18:
chr18:
AACTTACTTTGT
AACTTACTTTGT
2
19
2.74
1.46E−04
3′ss
CLL



66356291-66358531
66355002-66358531
TTATGATGCTTT
TTATGATGAGTA





TATTTTAGATTC
TGAAGATGGTGA





AGAG (693)
TCTG (694)





404
chr21:
chr21:
ATCATAGCCCAC
ATCATAGCCCAC
3
25
2.70
2.17E−02
3′ss
CLL



37416267-37417879
37416254-37417879
ATGTCCAGTTTT
ATGTCCAGGTAA





TCTTTCTAGGTA
AAGCAGCGTTTA





AAAG (695)
ATGA (696)





405
chrX:
chrX:
TGACTCCGCTGC
TGACTCCGCTGC
1
12
2.70
2.07E−02
3′ss
CLL



118923962-118925536
118923974-118925536
TCGCCATGACTT
TCGCCATGTCTT





TCAGGATTAAGC
CTCACAAGACTT





GATT (697)
TCAG (698)





406
chr1:
chr1:
CCAAGCACCTGA
CCAAGCACCTGA
7
50
2.67
1.87E−03
3′ss
CLL



100606070-100606400
100606070-100606522
AACAGCAGTTTG
AACAGCAGATGC





CAGGCTTCTATT
TGAAAAAGTTCA





TTAG (699)
CTTC (700)





407
chr12:
chr12:
GCCTGCCTTTGA
GCCTGCCTTTGA
13
88
2.67
1.74E−07
3′ss
CLL



113346629-113348840
113346629-113348855
TGCCCTGGATTT
TGCCCTGGGTCA





TGCCCGAACAGG
GTTGACTGGCGG





TCAG (71)
CTAT (72)





408
chr7:
chr7:
CGAGCTGTTGGC
CGAGCTGTTGGC
7
49
2.64
2.27E−05
3′ss
CLL



149547427-149549949
149547427-149556510
ATCCTTGGTTTC
ATCCTTGGGACC





TTGTCCACAGGA
TGCCGCTGCCAA





GAAG (701)
GCCA (702)





409
chr11:
chr11:
GCTTTCTACGGA
GCTTTCTACGGA
3
24
2.64
1.08E−04
3′ss
CLL



126142974-126143210
126142974-126143230
ACATCAATGAGC
ACATCAATGAGT





TTCTGTCTGCAC
ACCTGGCCGTAG





ACAG (703)
TCGA (704)





410
chr8:
chr8:
TTATTTTACACA
TTATTTTACACA
3
24
2.64
2.89E−05
3′ss
CLL



38095145-38095624
38095145-38095606
ATCCAAAGCCAG
ATCCAAAGCTTA





TTGCAGGGTCTG
TGGTGCATTACC





ATGA (57)
AGCC (58)





411
chr12:
chr12:
CAGGAATACCTG
CAGGAATACCTG
1
11
2.58
2.06E−06
3′ss
CLL



62783294-62783413
62783294-62783384
CAGATAAGATTT
CAGATAAGATGA





CACAGAATATTC
TAGTTACTGATA





GCTA (705)
TATA (706)





412
chr17:
chr17:
CTACACCAAGAA
CTACACCAAGAA
1
11
2.58
2.56E−03
3′ss
CLL



18007203-18007857
18007203-18007936
GAGAGGACCTCT
GAGAGGACAGAG





TCCCTCGCGCAG
GCCAGACTTCAC





AATC (707)
AGAC (708)





413
chr17:
chr17:
CGGAGGCTGTCT
CGGAGGCTGTCT
1
11
2.58
4.39E−03
3′ss
CLL



73486839-73487110
73486839-73487129
CCTCTCAGACTT
CCTCTCAGGAAA





CCTCTCTCCCAC
TGCTGCGCTGCA





CAGG (709)
TTTG (710)





414
chr11:
chr11:
TCCTGCTGGAGC
TCCTGCTGGAGC
0
5
2.58
5.77E−03
3′ss
CLL



68331900-68334466
68331900-68334481
CACCCAAGCTTT
CACCCAAGAAAA





TTCTTCTTCAGA
GTGTGATGAAGA





AAAG (711)
CCAC (712)





415
chr13:
chr13:
AGCTGAAATTTC
AGCTGAAATTTC
0
5
2.58
3.85E−02
3′ss
CLL



113915073-113917776
113915073-113917800
CAGTAAAGGGGG
CAGTAAAGCCTG





GTTTTATTCTTC
GAGATTTGAAAA





TTTT (152)
AGAG (153)





416
chr13:
chr13:
ACCAAGCATACT
ACCAAGCATACT
0
5
2.58
1.04E−02
3′ss
CLL



20656270-20656905
20656270-20656920
TCCAGATGTTCT
TCCAGATGGGTC





CTCTATTTAAGG
AATATTCTCTCG





GTCA (713)
AGTT (714)





417
chr19:
chr19:
CGGGCCGCCCCC
CGGGCCGCCCCC
0
5
2.58
1.76E−03
3′ss
CLL



36231397-36231924
36230989-36231924
CTGCCCGGTGTT
CTGCCCGGAGGC





CTTCTGGGCAGT
CGGTCCCTGCCA





GCAA (715)
AGGG (716)





418
chr20:
chr20:
ACATGAAGGTGG
ACATGAAGGTGG
0
5
2.58
3.36E−03
3′ss
CLL



34144042-34144761
34144042-34144743
ACGGAGAGTTCT
ACGGAGAGGTAC





CTGTGACCAGAC
TGAGGACAAATC





ATGA (250)
AGTT (50)





419
chr21:
chr21:
AAGATGTCCCTG
AAGATGTCCCTG
0
5
2.58
3.03E−02
3′ss
CLL



38570326-38572514
38570326-38572532
TGAGGATTGTGT
TGAGGATTGCAC





GTTTGTTTCCAC
TGGGTGCAAGTT





AGGC (224)
CCTG (225)





420
chr6:
chr6:
GGAGGACTGGGG
GGAGGACTGGGG
0
5
2.58
2.97E−03
3′ss
CLL



32095539-32095893
32095527-32095893
TCTGCAGACATT
TCTGCAGAACAG





TCTTGCAGACAG
CACCTTGTATTC





CACC (717)
TGGC (718)





421
chr7:
chr7:
CTGCCCCCTGCG
CTGCCCCCTGCG
0
5
2.58
7.48E−03
3′ss
CLL



44795898-44796008
44795898-44796023
CCACACGGCCTC
CCACACGGTGAT





TTTCCCTGCAGT
GGTTCATTCGCA





GATG (719)
TATG (720)





422
chr7:
chr7:
TGTAAATGGGGA
TGTAAATGGGGA
0
5
2.58
2.68E−02
3′ss
CLL



889240-889477
889240-889559
AGCGCTGTACTG
AGCGCTGTGCGA





CCATTGCTATGC
CGACTGTAAGGG





ACGG (721)
CAAG (595)





423
chr12:
chr12:
GGCCAGCCCCCT
GGCCAGCCCCCT
10
62
2.52
1.37E−08
3′ss
CLL



120934019-120934204
120934019-120934218
TCTCCACGGCCT
TCTCCACGGTAA





TGCCCACTAGGT
CCATGTGCGACC





AACC (206)
GAAA (207)





424
chr9:
chr9:
CTGATGAAAACT
CTGATGAAAACT
11
66
2.48
1.51E−04
3′ss
CLL



93641235-93648124
93641235-93650030
ACTACAAGCAGA
ACTACAAGGCCC





CACCTTACAGGC
AGACCCATGGAA





CAGG (722)
AGTG (723)





425
chr17:
chr17:
TTCAGCTGCCCC
TTCAGCTGCCCC
8
49
2.47
1.42E−05
3′ss
CLL



57079102-57089688
57079075-57089688
TGAAGAAGAAAC
TGAAGAAGGAAT





ATGTTCTCCTTC
GAGTAGCGACAG





CTTC (724)
TGAC (725)





426
chr15:
chr15:
GAAACCAACTAA
GAAACCAACTAA
3
21
2.46
9.18E−03
3′ss
CLL



59209219-59224554
59209198-59224554
AGGCAAAGCCCA
AGGCAAAGGTAA





TTTTCCTTCTTT
AAAACATGAAGC





CGCA (101)
AGAT (102)





427
chr7:
chr7:
TCCCGAAGCCAC
TCCCGAAGCCAC
3
21
2.46
4.67E−04
3′ss
CLL



99752804-99752884
99752787-99752884
CTCATGAGCCTC
CTCATGAGGTCG





TGCCTTCCCCCA
GGCAGTGTGATG





GGTC (726)
GAGC (727)





428
chr8:
chr8:
CCCCGGTGCGTA
CCCCGGTGCGTA
1
10
2.46
2.22E−02
3′ss
CLL



145624052-145624168
145624028-145624168
AGGAGGAGCCTG
AGGAGGAGGAGG





CCCCCCTTTGGC
ACAATCCCAAGG





CCTG (728)
GGGA (729)





429
chr9:
chr9:
AGCTGGAGAAAA
AGCTGGAGAAAA
1
10
2.46
3.34E−04
3′ss
CLL



123932094-123935634
123932094-123935520
ACCTTCTTTTTC
ACCTTCTTATGG





TTCCAGAACTAC
CAAACCAAAAAG





CAGC (730)
ATTT (731)





430
chr15:
chr15:
TTCGTTGGCAGC
TTCGTTGGCAGC
6
37
2.44
2.59E−04
3′ss
CLL



77327904-77328151
77327904-77328142
TTCTGCTGAGAC
TTCTGCTGCGTC





CCTGACCCCCAC
CACAGAGACCCT





CCCC (732)
GACC (733)





431
chr19:
chr19:
GTGCTTGGAGCC
GTGCTTGGAGCC
5
31
2.42
4.69E−03
3′ss
CLL



55776746-55777253
55776757-55777253
CTGTGCAGACTT
CTGTGCAGCCTG





TCCGCAGGGTGT
GTGACAGACTTT





GCGC (179)
CCGC (180)





432
chr4:
chr4:
GTGCCAACGAGG
GTGCCAACGAGG
10
57
2.40
1.64E−03
3′ss
CLL



184577127-184580081
184577114-184580081
ACCAGGAGTTCT
ACCAGGAGATGG





TTATTTCAGATG
AACTAGAAGCAT





GAAC (734)
TACG (735)





433
chr16:
chr16:
CCTCACGATGCA
CCTCACGATGCA
7
40
2.36
8.53E−04
3′ss
CLL



67692735-67692830
67692719-67692830
AGGCCACGAGTT
AGGCCACGGGAG





CATGTCCCACAG
AAGCTGTGTACA





GGAG (736)
CTGT (737)





434
chr6:
chr6:
AGGGGGCTCTTT
AGGGGGCTCTTT
14
75
2.34
3.51E−06
3′ss
CLL



91269953-91271340
91269933-91271340
ATATAATGTTTG
ATATAATGTGCT





TGCCTTTCTTTC
GCATGGTGCTGA





GCAG (265)
ACCA (266)





435
chr15:
chr15:
TCACACAGGATA
GCCTCACTGAGC
2
14
2.32
4.92E−03
exon
CLL



25212299-25213078
25207356-25213078
ATTTGAAAGTGT
AACCAAGAGTGT




incl.





CAGTTGTACCCG
CAGTTGTACCCG





AGGC (164)
AGGC (145)





436
chr9:
chr9:
AAAAATAAAGCC
CTGATGAAAACT
1
9
2.32
3.99E−03
5′ss
CLL



93648256-93650030
93641235-93650030
TTTCCCAGGCCC
ACTACAAGGCCC





AGACCCATGGAA
AGACCCATGGAA





AGTG (738)
AGTG (723)





437
chr14:
chr14:
CGAGGATGAAGA
CGAGGATGAAGA
0
4
2.32
4.50E−03
3′ss
CLL



34998676-35002649
34998681-35002649
CAGAGCAGGTGA
CAGAGCAGTACA





CCAAGAAAAAAA
GGTGACCAAGAA





AGAA (739)
AAAA (740)





438
chr2:
chr2:
AGACAAGGGATT
AGACAAGGGATT
0
4
2.32
1.21E−02
3′ss
CLL



26437445-26437921
26437430-26437921
GGTGGAAACATT
GGTGGAAAAATT





TTATTTTACAGA
GACAGCGTATGC





ATTG (295)
CATG (296)





439
chrX:
chrX:
AAAAGAAACTGA
AAAAGAAACTGA
16
82
2.29
2.84E−08
3′ss
CLL



129771378-129790554
129771384-129790554
GGAATCAGTATC
GGAATCAGCCTT





ACAGGCAGAAGC
AGTATCACAGGC





TCTG (303)
AGAA (304)





440
chr1:
chr1:
TTCCCCATCAAC
TTCCCCATCAAC
5
28
2.27
4.85E−06
3′ss
CLL



19480448-19481411
19480433-19481411
ATCAAAAGTTTT
ATCAAAAGTTCC





GTTGTCTGCAGT
AATGGTGGCAGT





TCCA (202)
AAGA (203)





441
chr3:
chr3:
AAAATGGGCTCA
AAAATGGGCTCA
10
52
2.27
1.39E−04
3′ss
CLL



141896447-141900302
141896418-141900302
GCAGTTAGGGTT
GCAGTTAGACCT





TTTTGTTGTTTG
TTTCACAGATGC





TTTG (741)
TGCT (742)





442
chr1:
chr1:
AAGCACTGGCCC
AAGCACTGGCCC
4
22
2.20
2.08E−02
3′ss
CLL



156553242-156553591
156553242-156553588
AGTGTCAGGAGC
AGTGTCAGAAGG





CAGATTCTGTGC
AGCCAGATTCTG





GAGA (743)
TGCG (744)





443
chr19:
chr19:
AGCCATTTATTT
AGCCATTTATTT
11
53
2.17
2.14E−08
3′ss
CLL



9728842-9730107
9728855-9730107
GTCCCGTGGGAA
GTCCCGTGGGTT





CCAATCTGCCCT
TTTTTCCAGGGA





TTTG (160)
ACCA (161)





444
chr15:
chr15:
CCACTCTCACAA
CCACTCTCACAA
1
8
2.17
1.41E−02
3′ss
CLL



91448953-91449151
91448953-91449074
TGACCCAGGAGG
TGACCCAGGCTG





ACCCCCGGCGGC
GATCAAGACCTT





GCTT (745)
TGAC (746)





445
chr1:
chr1:
TTGGAAGCGAAT
TTGGAAGCGAAT
1
8
2.17
4.59E−02
3′ss
CLL



23398690-23399766
23398690-23399784
CCCCCAAGTCCT
CCCCCAAGTGAT





TTGTTCTTTTGC
GTATATCTCTCA





AGTG (210)
TCAA (211)





446
chr2:
chr2:
CCTTTACTTGGG
AACCCGGAGAGA
1
8
2.17
4.13E−02
5′ss
CLL



64457092-64478252
64456774-64478252
GCTCTCAGCAAC
AAAGGGAGCAAC





TGATGTTGCCAT
TGATGTTGCCAT





GCAG (747)
GCAG (578)





447
chr14:
chr14:
GTGGGGGGCCAT
GTGGGGGGCCAT
16
75
2.16
9.79E−09
3′ss
CLL



23237380-23238985
23237380-23238999
TGCTGCATTTTG
TGCTGCATGTAC





TATTTTCCAGGT
AGTCTTTGCCCG





ACAG (122)
CTGC (123)





448
chr15:
chr15:
ACTCAGATGCCG
ACTCAGATGCCG
14
65
2.14
1.32E−05
3′ss
CLL



74326871-74327483
74326871-74327512
AAAACTCGCCCT
AAAACTCGTGCA





CAGTCTGAGGTT
TGGAGCCCATGG





CTGT (748)
AGAC (749)





449
chr10:
chr10:
GCCTACTCTTAA
TCATCTTGAAAA
7
34
2.13
4.92E−03
exon
CLL



89516679-89519457
89516679-89527429
CCATTAGGGTGG
ATGAAAATGTGG




incl.





ATAGGCATGTAG
ATAGGCATGTAG





ACCT (750)
ACCT (507)





450
chr20:
chr20:
TGGAGTGCGGAT
TGGAGTGCGGAT
2
12
2.12
4.37E−03
3′ss
CLL



33703761-33706400
33703736-33706400
TTGCAACACTTG
TTGCAACAATCA





CTTCCTTCTCCC
AAGATCTGCGAG





ACAT (751)
ACCA (752)





451
chr12:
chr12:
CAACTGGAGTTC
CAACTGGAGTTC
12
53
2.05
3.67E−06
3′ss
CLL



105514375-105514866
105514375-105514878
ATTTTCAGGTTT
ATTTTCAGACTA





TTTGACAGACTA
TGTATGAGCACT





TGTA (753)
TGGG (754)





452
chr1:
chr1:
CAATGTGTTGAC
CAATGTGTTGAC
14
61
2.05
1.87E−03
3′ss
CLL



155237988-155238083
155237937-155238083
CATCGCAGTCCC
CATCGCAGCCTC





CCTACAGCCCTG
TCCTGCCAACTT





TTCA (755)
ACAG (756)





453
chr15:
chr15:
CAGCTGCTCTCA
CAGCTGCTCTCA
16
67
2.00
7.47E−04
3′ss
CLL



89870310-89870397
89870294-89870397
GGAGAGAGTGGA
GGAGAGAGGTAC





CTGGCTCTGTAG
AAAGAAGACCCC





GTAC (757)
TGGC (758)





454
chr3:
chr3:
TCTCTAGTGGGC
TCTCTAGTGGGC
8
35
2.00
7.53E−03
3′ss
CLL



141272782-141274647
141272782-141274681
CCTTCTAGTTCT
CCTTCTAGGAAT





ACAAGGTAAAAC
GACCAAAAGAAG





TCTA (759)
ACAA (760)





455
chr1:
chr1:
AGCTCCGAGAGG
AGCTCCGAGAGG
2
11
2.00
6.28E−03
3′ss
CLL



202122978-202123313
202122963-202123313
GCAAGGAGCTCC
GCAAGGAGAAAT





CTCCCTCCTAGA
GTGTCCACTACT





AATG (761)
GGCC (762)





456
chrX:
chrX:
GACGTGGCAGCT
GACGTGGCAGCT
19
73
1.89
1.20E−04
3′ss
CLL



47315813-47326808
47315797-47326808
CATGTGAGCATT
CATGTGAGGCTT





GTGTCGTTACAG
CAGTGTCATTTG





GCTT (763)
AGGA (764)





457
chr6:
chr6:
AAGGAAGAACAA
AATGTTAAGGAG
2
10
1.87
4.93E−04
exon
CLL



25975158-25983391
25973513-25983391
GACTTTGTTTAG
TCATCAAGTTAG




incl.





TGTGACTCTGGA
TGTGACTCTGGA





TCCA (765)
TCCA (766)





458
chr11:
chr11:
AGGAGAACACCT
AGGAGAACACCT
15
55
1.81
1.53E−04
3′ss
CLL



10876665-10877690
10876633-10877690
TATTTCAGCTTT
TATTTCAGAAAA





TATTTTTATGTG
GGTGTACCATAC





ATAA (767)
CTGA (768)





459
chr9:
chr9:
CTGATGAAAACT
CTGATGAAAACT
12
43
1.76
4.16E−05
3′ss
CLL



93641235-93648127
93641235-93650030
ACTACAAGACAC
ACTACAAGGCCC





CTTACAGGCCAG
AGACCCATGGAA





GAGA (769)
AGTG (723)





460
chr8:
chr8:
GGGGCCACCAGG
GGGGCCACCAGG
21
72
1.73
2.11E−05
3′ss
CLL



145313817-145314126
145313817-145314142
TTGGCCAGCGGC
TTGGCCAGGGCC





CCCCTTTCCCAG
ATGGCTGAGCAC





GGCC (770)
GCAG (771)





461
chr7:
chr7:
TGCACACGCCTC
TGCACACGCCTC
4
15
1.68
2.26E−02
3′ss
CLL



98579583-98580862
98579583-98580886
TCCTACAGAGTC
TCCTACAGGCAG





TCTTATGCTGGT
CCCAGCAAATCA





CCCA (772)
TCGA (773)





462
chr22:
chr22:
GAGCTGGAGAGG
GAGCTGGAGAGG
14
46
1.65
2.74E−04
3′ss
CLL



50660983-50662569
50661021-50662569
AAGGCGAGAGGC
AAGGCGAGGCAG





AGCTCGTCGGGA
GCACTGGTCGAC





GCAG (774)
CACT (775)





463
chr6:
chr6:
GCCCCCGTTTTC
GCCCCCGTTTTC
17
55
1.64
1.17E−04
3′ss
CLL



31936315-31936399
31936315-31936462
CTGCCCAGCCCT
CTGCCCAGTACC





TGTCCTCAGTGC
TGAAGCTGCGGG





ACCC (307)
AGCG (308)





464
chr7:
chr7:
CCGCCTCTGCCT
CCGCCTCTGCCT
8
26
1.58
3.53E−03
3′ss
CLL



64139714-64150776
64139714-64144464
TCGGATAGGTCT
TCGGATAGGAAA





GGCCCCACCCTG
GGTTGAAAGAGC





GAGT (776)
CAAC (777)





465
chr12:
chr12:
TTTCTCATATTG
TTTCTCATATTG
5
17
1.58
4.42E−03
3′ss
CLL



51174021-51189680
51174021-51189691
CTCAACAGTTCT
CTCAACAGGTAT





TTTTTAGGTATC
CATCTTTATCAG





ATCT (778)
AAAG (779)





466
chr11:
chr11:
AGTGGCTTTGGC
AGTGGCTTTGGC
15
46
1.55
1.99E−03
intron
CLL



126144916-126144918
126144916-126145221
GTCTTATGGAGG
GTCTTATGGGAT




reten-





CTTGCTTGCAGA
GGAGGACGAAGG




tion





GGGG (780)
TTGG (781)





467
chr1:
chr1:
CATAGTGGAAGT
CATAGTGGAAGT
20
60
1.54
6.97E−06
3′ss
CLL



67890660-67890765
67890642-67890765
GATAGATCTTCT
GATAGATCTGGC





TTTTCACATTAC
CTGAAGCACGAG





AGTG (444)
GACA (445)





468
chr1:
chr1:
GGTGACACTCAA
GGTGACACTCAA
22
65
1.52
1.10E−05
3′ss
CLL



157771381-157771704
157771367-157771704
CTTCACAGGTCT
CTTCACAGTGCC





CTCCCTCTAGTG
TACTGGGGCCAG





CCTA (782)
AAGC (783)





469
chr2:
chr2:
GGCAACTTCGTT
GGCAACTTCGTT
27
76
1.46
7.08E−07
3′ss
CLL



106781255-106782511
106781240-106782511
AATATGAGCTTT
AATATGAGGTCT





CTACTCAACAGG
ATCCAGGAAAAT





TCTA (375)
GGTG (376)





470
chr14:
chr14:
CGCTCTCCGCCT
AGGGAGACGTTC
19
54
1.46
2.09E−04
exon
CLL



75348719-75352288
75349327-75352288
TCCAGAAGGGGT
CCTGCCTGGGGT




skip





CTCCTTATGCCA
CTCCTTATGCCA





GGGA (208)
GGGA (209)





471
chr2:
chr2:
TTTCCATTGGGC
GAGGGCCACCAA
3
10
1.46
4.35E−02
exon
CLL



153551136-153571063
153551136-153572508
CAATCAAGATGC
TGGGACAAATGC




incl.





CTGGAATGATGT
CTGGAATGATGT





CGTC (784)
CGTC (785)





472
chrX:
chrX:
AGAGACAAAGAG
AGAGACAAAGAG
33
92
1.45
4.85E−06
3′ss
CLL



118759359-118763280
118759342-118763280
AAGAAAAACTCT
AAGAAAAATTAA





TACTGTTTTACA
CTCTGCTGTTTG





GTTA (786)
CTGC (787)





473
chr17:
chr17:
CTCACCAGCGCC
CTCACCAGCGCC
5
15
1.42
1.43E−03
exon
CLL



27238402-27239499
27238255-27239499
ATCGTCAGCTCT
ATCGTCAGATGG




incl.





AGGAGTTCCAGA
CAAGGTCAGCCC





GCCT (788)
CGGC (789)





474
chr12:
chr12:
ATCAGGTGCTCA
ATCAGGTGCTCA
11
30
1.37
9.13E−04
3′ss
CLL



50821692-50822699
50821692-50822717
TCCTGAGGTGTC
TCCTGAGGGTAA





TGTCTTTAATAC
TGCAGAGCTCTC





AGGT (790)
AGAA (791)





475
chr6:
chr6:
TCTGGCAGCCCA
TCTGGCAGCCCA
17
45
1.35
1.98E−04
3′ss
CLL



43152643-43153228
43152643-43153193
CGATGCTGCAAG
CGATGCTGGGAG





ATGGCATCGAGC
TCGGGCTCACGT





AGCA (792)
CCTT (793)





476
chr3:
chr3:
AGAATTTTAAGA
AGAATTTTAAGA
11
29
1.32
1.64E−03
3′ss
CLL



3186394-3188099
3186394-3188113
TACTTCAGATTT
TACTTCAGGTTT





TGTCTTGTAGGT
TATGGGAGAATT





TTTA (794)
GTAG (795)





477
chr7:
chr7:
CCGCCTCTGCCT
CCGCCTCTGCCT
1
4
1.32
2.43E−02
3′ss
CLL



64139714-64150765
64139714-64144464
TCGGATAGGCTT
TCGGATAGGAAA





TATTTAGGTCTG
GGTTGAAAGAGC





GCCC (796)
CAAC (777)





478
chr3:
chr3:
GAGCTAGTCAGA
AAATTCTTGACC
15
38
1.29
1.66E−02
exon
CLL



56606456-56626997
56605330-56626997
CTTTAGAGGAAA
AATCTAGGGAAA




incl.





CAGTACTGCTGG
CAGTACTGCTGG





AGCA (797)
AGCA (798)





479
chr22:
chr22:
CTTCATCTGTGG
CTTCATCTGTGG
25
61
1.25
5.02E−06
3′ss
CLL



24043032-24047615
24037704-24047615
ATAAGCAGGTCA
ATAAGCAGTGCA





TGTCCTCCAGGT
GGCCAAGGCCCC





TTCT (799)
CTGC (800)





480
chr17:
chr17:
CCGGAGCCCCTT
CCGGAGCCCCTT
8
20
1.22
1.07E−02
3′ss
CLL



45229302-45232037
45229284-45232037
CAAAAAAGACTT
CAAAAAAGTCTG





TTCGTGTTTTAC
TTGCCAGAATCG





AGTC (327)
GCCA (328)





481
chr1:
chr1:
AGTATGGGATAT
TCATTCTTATTT
8
20
1.22
2.03E−02
exon
CLL



62149218-62152463
62149218-62160368
TTTAAAAGATTG
CAATGCAGATTG




incl.





TTGGACCTTCAG
TTGGACCTTCAG





ATGG (801)
ATGG (802)





482
chr22:
chr22:
CTTTATCTGTGC
CTTCATCTGTGG
31
73
1.21
1.26E−05
exon
CLL



24037704-24042912
24037704-24047615
ATGAACAGTGCA
ATAAGCAGTGCA




incl.





GGCCAAGGCCCC
GGCCAAGGCCCC





CTGC (803)
CTGC (800)





483
chr7:
chr7:
AAGTCGTCCTCT
AGAGAGAAACAT
18
42
1.18
2.78E−02
exon
CLL



104844232-104909252
104844232-105029094
TCAGAAAGGCCG
CCGAAAAAGCCG




incl.





GAGCCTCAACAG
GAGCCTCAACAG





AAAG (804)
AAAG (805)





484
chr2:
chr2:
TGGGCTACCTTA
TGGGCTACCTTA
23
53
1.17
3.28E−02
exon
CLL



85779690-85780061
85779104-85780061
ACCCTGGGGTAT
ACCCTGGGGATT




incl.





TTACACAGAGTC
TTTGACCCTCGT





GGCG (806)
GTGG (807)





485
chr1:
chr1:
GACTGCCCTAAA
GACTGCCCTAAA
10
23
1.13
4.92E−03
3′ss
CLL



52902647-52903891
52902635-52903891
AGGAAAAGTTTA
AGGAAAAGACTA





CTGTTTAGACTA
AAGAAGAAAGAC





AAGA (808)
AGTG (809)





486
chr3:
chr3:
TGATAGTTGGAG
TGATAGTTGGAG
11
25
1.12
3.47E−03
3′ss
CLL



179065598-179066635
179065598-179066632
CGGAGACTCATA
CGGAGACTTAGC





ATGGCAGAACCT
ATAATGGCAGAA





GTTT (810)
CCTG (811)





487
chr1:
chr1:
TCATTCTTATTT
TCATTCTTATTT
5
12
1.12
3.19E−02
exon
CLL



62152593-62160368
62149218-62160368
CAATGCAGAGAC
CAATGCAGATTG




incl.





AGGGTCTTGCTC
TTGGACCTTCAG





TGTT (812)
ATGG (802)





488
chr19:
chr19:
TGACGGTGCCAC
TGACGGTGCCAC
30
65
1.09
4.13E−02
exon
CLL



53935281-53936832
53935281-53945048
CGCGGCGCTTTT
CGCGGCGCAGAG




incl.





CTCCCTTAGATG
GAGTCTGCAATG





CCTT (813)
CCGA (814)





489
chr19:
chr19:
GCAGTGGCTGGA
GCAGTGGCTGGA
42
85
1.00
4.02E−05
3′ss
CLL



19414656-19416657
19414721-19416657
GATCAAAGTTTC
GATCAAAGAGAG





ACCCCCAGAGGG
AGTGTGCCTATT





AGCC (815)
GACT (816)





490
chrX:
chrX:
GGACGATGGGGA
GGACGATGGGGA
3
7
1.00
8.68E−03
3′ss
CLL



47103949-47104083
47103949-47104080
TGAGAAAGATGA
TGAGAAAGAAGA





CGAGGAGGATAA
TGACGAGGAGGA





AGAT (817)
TAAA (818)





491
chr5:
chr5:
ACTCTTATGCAG
ACTCTTATGCAG
24
48
0.97
7.63E−03
3′ss
CLL



1579599-1585098
1581810-1585098
TCCCCATGGACT
TCCCCATGAGGA





GAACCATCAAGA
GATCCTAGTCTC





CACC (819)
ACCA (531)





492
chr17:
chr17:
GACCCATGCATC
GACCCATGCATC
47
93
0.97
2.22E−02
3′ss
CLL



73587327-73587681
73587327-73587696
CTCCTGTGCTCC
CTCCTGTGTGGG





TCCCACTGCAGT
CACAGTGGCTCA





GGGC (820)
GGGA (821)





493
chr18:
chr18:
CCAAGTTTTGTG
CCAAGTTTTGTG
38
75
0.96
7.90E−03
3′ss
CLL



224200-224923
224179-224923
AAAGAAAGTGTA
AAAGAAAGAACA





TGTTTTGTTCAC
TCAGATACCAAA





GACA (116)
CCTA (117)





494
chr16:
chr16:
CATCAAGCAGCT
CATCAAGCAGCT
10
20
0.93
2.86E−02
3′ss
CLL



57473207-57474683
57473246-57474683
GTTGCAATGTTT
GTTGCAATCTGC





AGTCCCAGGAAG
CCACAAAGAATC





CACC (822)
CAGC (823)





495
chr7:
chr7:
TGAGAGTCTTCA
TGAGAGTCTTCA
45
86
0.92
7.69E−08
3′ss
CLL



99943591-99947339
99943591-99947421
GTTACTAGTTTG
GTTACTAGAGGC





TCTTTCCTAGAT
GGATTTCCCTGA





CCAG (420)
CTGA (421)





496
chr12:
chr12:
CAATCATTGACA
CAATCATTGACA
29
54
0.87
3.27E−02
3′ss
CLL



47599928-47600293
47599852-47600293
ATATTATGACCC
ATATTATGGAAC





TGCATGTGATGG
TGACTCAGCGCA





ATCA (824)
AGAA (825)





497
chr9:
chr9:
GGGACACTGTGC
GGGACACTGTGC
43
72
0.73
1.74E−02
3′ss
CLL



140633231-140637822
140633231-140637843
CGAATGAACTTG
CGAATGAACAGC





CTTGCCTTTTGT
TGCAGTATCTCG





TTTA (826)
GAAG (827)





498
chr19:
chr19:
TCAGGGGGCGCG
TCGAGCCAGGCT
10
17
0.71
2.37E−02
exon
CLL



17654242-17657494
17654440-17657494
TGCTGAAGGAGC
GCAAAAAGGAGC




skip





TGCCTGAGTTCG
TGCCTGAGTTCG





AGGG (828)
AGGG (829)





499
chr6:
chr6:
CTACAACCAGAG
CTACAACCAGAG
57
92
0.68
2.50E−03
3′ss
CLL



29691704-29691949
29691704-29691966
CGAGGCTGGGTC
CGAGGCTGGGAA





TCACACCCTCCA
TGAATGGCTGCG





GGGA (830)
ACAT (831)





500
chr20:
chr20:
TGCCTAAGGCGG
TGCCTAAGGCGG
54
87
0.68
4.59E−02
3′ss
CLL



30310151-30310420
30310133-30310420
ATTTGAATCTCT
ATTTGAATAATC





TTCTCTCCCTTC
TTATCTTGGCTT





AGAA (479)
TGGA (480)





501
chr4:
chr4:
TCCAACAAGCAC
TCCAACAAGCAC
55
87
0.65
1.64E−04
3′ss
CLL



17806394-17806729
17806379-17806729
CTCTGAAGTCTT
CTCTGAAGGTTA





CTCATTCACAGG
AGGCTACCTTTC





TTAA (832)
CAGA (833)





502
chr9:
chr9:
CACCACAAAATC
CACCACAAAATC
41
65
0.65
4.07E−03
3′ss
CLL



140622981-140637822
140622981-140637843
ACAGACAGCTTG
ACAGACAGCAGC





CTTGCCTTTTGT
TGCAGTATCTCG





TTTA (458)
GAAG (459)





503
chr1:
chr1:
GAATCCGTATCT
GAATCCGTATCT
45
70
0.63
4.59E−02
3′ss
CLL



155278756-155279833
155278756-155279854
GGGAACAGAGCC
GGGAACAGAATG





CTTTGCTCCTCC
AACGGAGACCAG





CTCA (432)
AATT (433)





504
chr17:
chr17:
GTTCCCGAGGCT
GTTCCCGAGGCT
60
90
0.58
8.49E−05
3′ss
CLL



40690773-40692967
40690773-40695045
GTCACCAGGGTG
GTCACCAGTGGA





TTCCCTCAGGTC
TACTGAGGCTGT





AATG (834)
GTGG (835)





505
chr12:
chr12:
ATTTCCAGAGGA
ATTTCCAGAGGA
51
76
0.57
1.45E−05
3′ss
CLL



95660408-95663814
95660408-95663826
TTTACACTTTTG
TTTACACTGGTC





CTTGACAGGGTC
AGTGCTGCTTGC





AGTG (462)
CCAT (463)





506
chr3:
chr3:
CCAGATCAACAC
CCAGATCAACAC
44
65
0.55
2.77E−02
3′ss
CLL



133371473-133372188
133371458-133372188
AATTGATAGTCG
AATTGATAATGT





TACTCTTTCAGA
CAGCAATATTTC





TGTC (836)
CAAC (837)





507
chr19:
chr19:
CGTCCTGCCCCC
CGTCCTGCCCCC
67
94
0.48
2.30E−02
3′ss
CLL



7075116-7075665
7075116-7075686
AACTGCCGCTCT
AACTGCCGCCTC





GTCTTCCCTGTT
TCAGCGAGAAGG





CCCA (838)
ACAC (839)





508
chr10:
chr10:
TGACGTTCTCTG
TGACGTTCTCTG
53
74
0.47
2.22E−03
3′ss
CLL



75554088-75554298
75554088-75554313
TGCTCCAGTGGT
TGCTCCAGGTTC





TTCTCCCACAGG
CCGGCCCCCAAG





TTCC (466)
TCGC (467)





509
chr19:
chr19:
TGCAGGGGGAGC
TGCAGGGGGAGC
48
66
0.45
6.62E−03
3′ss
CLL



11558433-11558507
11558433-11558537
AGCCCAAGGAGG
AGCCCAAGCCGG





CCCCACCGCCAC
CCAGCCCTGCTG





TGTC (840)
AGGA (841)





510
chr1:
chr1:
GACTGCCCTAAA
GACTGCCCTAAA
55
74
0.42
8.74E−03
3′ss
CLL



52902650-52903891
52902635-52903891
AGGAAAAGCAGT
AGGAAAAGACTA





TTACTGTTTAGA
AAGAAGAAAGAC





CTAA (842)
AGTG (809)





511
chr17:
chr17:
CTATGAGGCCAT
GTTCCCGAGGCT
68
87
0.35
1.45E−03
exon
CLL



40693224-40695045
40690773-40695045
GACTGCAGTGGA
GTCACCAGTGGA




incl.





TACTGAGGCTGT
TACTGAGGCTGT





GTGG (843)
GTGG (835)





512
chr5:
chr5:
CTTCTCAAGATC
CTTCTCAAGATC
70
86
0.29
2.73E−02
3′ss
CLL



139865317-139866542
139865317-139866590
AGTCTCAGGTGC
AGTCTCAGGAAC





CACGTGTGCCAA
CTGACAGAACTT





CGCA (844)
CACA (845)





513
chr6:
chr6:
ACCTTAACAAGA
AATCACTAGGAA
58
71
0.29
1.38E−02
exon
CLL



127636041-127637594
127636041-127648146
TTTATGAGACTT
CTCCAGAGACTT




incl.





CCTTTAATAAGT
CCTTTAATAAGT





GTTG (846)
GTTG (847)





514
chr4:
chr4:
ACTGGGCTTCCA
ACTGGGCTTCCA
60
72
0.26
4.54E−02
exon
CLL



54266006-54280781
54266006-54292038
CCGAGCAGAAAC
CCGAGCAGGAGA




incl.





AGCACTTCTTCT
TTACCTGGGGCA





CAGT (848)
ATTG (849)





515
chr9:
chr9:
CTGAAGACGGGA
CTGAAGACGGGA
87
92
0.08
2.80E−02
3′ss
CLL



130566979-130569251
130566979-130569270
TTCTTTAGCTCT
TTCTTTAGGTTC





CCCCACCTGGTG
GGGAGCGGATCC





CAGG (850)
GCAT (851)





516
chr17:
chr17:
ATCTCAGGAGCA
CCCACCCCTTCA
93
98
0.07
4.18E−03
5′ss
CLL



72759659-72763074
72760785-72763074
CCTGAATGGTCC
CCCTGCAGGTCC





CCTGCCTGTGCC
CCTGCCTGTGCC





CTTC (852)
CTTC (853)





517
chr2:
chr2:
AGCAAGTAGAAG
AGCAAGTAGAAG
0
72
6.19
1.51E−10
3′ss
Mel.



109102364-109102954
109102364-109102966
TCTATAAAATTT
TCTATAAAATAC





ACCCCCAGATAC
AGCTGGCTGAAA





AGCT (1)
TAAC (2)





518
chr19:
chr19:
GGCCCTTTTGTC
GGCCCTTTTGTC
0
72
6.19
7.67E−09
3′ss
Mel.



57908542-57909780
57908542-57909797
CTCACTAGCATT
CTCACTAGGTTC





TCTGTTCTGACA
TTGGCATGGAGC





GGTT (7)
TGAG (8)





519
chr2:
chr2:
TGACCACGGAGT
TGACCACGGAGT
0
59
5.91
1.12E−08
3′ss
Mel.



232196609-232209660
232196609-232209686
ACCTGGGGCCCT
ACCTGGGGATCA





TTTTTCTCTTTC
TGACCAACACGG





CTTC (37)
GGAA (38)





520
chr1:
chr1:
CAAGTATATGAC
CAAGTATATGAC
0
56
5.83
3.98E−05
3′ss
Mel.



245246990-245288006
245246990-245250546
TGAAGAAGATCC
TGAAGAAGGTGA





TGAATTCCAGCA
GCCTTTTTCTCA





AAAC (21)
AGAG (22)





521
chr11:
chr11:
GGCCACACGCCT
GGCCACACGCCT
0
54
5.78
1.58E−06
3′ss
Mel.



65635911-65635980
65635892-65635980
CTGCCAAGCCCC
CTGCCAAGACAT





TCTCCCCTGGCA
TGATGAGTGTGA





CAGA (854)
GTCT (855)





522
chr3:
chr3:
TGCAGTTTGGTC
TGCAGTTTGGTC
0
49
5.64
5.19E−07
3′ss
Mel.



9960293-9962150
9960293-9962174
AGTCTGTGCCTT
AGTCTGTGGGCT





CCTCACCCCTCT
CTGTGGTATATG





CCTC (23)
ACTG (24)





523
chr3:
chr3:
GAGTACGAGGTC
GAGTACGAGGTC
0
48
5.61
2.52E−15
3′ss
Mel.



48457878-48459319
48457860-48459319
TCCAGCAGCCTG
TCCAGCAGCCTC





CCCTGTGCCTAC
GTGTGCATCACC





AGCC (856)
GGGG (857)





524
chr10:
chr10:
TACCTCTGGTTC
TACCTCTGGTTC
0
47
5.58
5.54E−06
3′ss
Mel.



99214556-99215395
99214556-99215416
CTGTGCAGTCTT
CTGTGCAGTTCT





CGCCCCTCTTTT
GTGGCACTTGCC





CTTA (13)
CTGG (14)





525
chr1:
chr1:
TCTTTGGAAAAT
TCTTTGGAAAAT
0
45
5.52
3.06E−06
3′ss
Mel.



101458310-101460665
101458296-101460665
CTAATCAATTTT
CTAATCAAGGGA





CTGCCTATAGGG
AGGAAGATCTAT





GAAG (25)
GAAC (26)





526
chr9:
chr9:
AGCGCATCGCAG
AGCGCATCGCAG
0
45
5.52
1.42E−03
3′ss
Mel.



90582559-90584108
90582574-90584108
CTTCCAAGTACT
CTTCCAAGGCTC





TCTTCACAGCTC
TCCTCCATCAGT





CCCT (858)
ACTT (859)





527
chr1:
chr1:
TCACTCAAACAG
TCACTCAAACAG
0
44
5.49
1.90E−07
3′ss
Mel.



179835004-179846373
179834989-179846373
TAAACGAGTTTT
TAAACGAGGTAT





ATCATTTACAGG
GTGACGCATTCC





TATG (53)
CAGA (54)





528
chr14:
chr14:
AGTTAGAATCCA
AGTTAGAATCCA
0
41
5.39
4.30E−08
3′ss
Mel.



74358911-74360478
74358911-74360499
AACCAGAGTGTT
AACCAGAGCTCC





GTCTTTTCTCCC
TGGTACAGTTTG





CCCA (61)
TTCA (62)





529
chr11:
chr11:
TGGGCAGCCCCC
TGGGCAGCCCCC
0
39
5.32
2.61E−02
3′ss
Mel.



117167925-117186250
117167677-117186250
CGCAGACGTTGG
CGCAGACGCTCA





TTTTTCAGCAGA
ACATCCTGGTGG





CCTG (860)
ATAC (861)





530
chr20:
chr20:
AGAACTGCACCT
AGAACTGCACCT
0
36
5.21
6.58E−07
3′ss
Mel.



62701988-62703210
62701988-62703222
ACACACAGCCCT
ACACACAGGTGC





GTTCACAGGTGC
AGACCCGCAGCT





AGAC (29)
CTGA (30)





531
chr18:
chr18:
AGAAAGAGCATA
AGAAAGAGCATA
0
33
5.09
6.82E−09
3′ss
Mel.



33605641-33606862
33573263-33606862
AATTGGAAATAT
AATTGGAAGAGT





TGGACATGGGCG
ACAAGCGCAAGC





TATC (91)
TAGC (92)





532
chr3:
chr3:
AACCAAGAGGAC
AACCAAGAGGAC
0
32
5.04
1.83E−02
3′ss
Mel.



52283338-52283671
52283338-52283685
CCACACAGGATG
CCACACAGGTTC





GTCTTCACAGGT
TCAAAGCTGGCC





TCTC (862)
CAGA (863)





533
chr9:
chr9:
AAATGAAGAAAC
AAATGAAGAAAC
0
32
5.04
6.82E−09
3′ss
Mel.



125759640-125760854
125759640-125760875
TCCTAAAGCCTC
TCCTAAAGATAA





TCTCTTTCTTTG
AGTCCTGTTTAT





TTTA (67)
GACC (68)





534
chr12:
chr12:
AATATTGCTTTA
AATATTGCTTTA
0
31
5.00
9.14E−06
3′ss
Mel.



116413154-116413319
116413118-116413319
CCAAACAGGGAC
CCAAACAGGTCA





CCCTTCCCCTTC
CGGAGGAGTAAA





CCCA (77)
GTAT (78)





535
chr18:
chr18:
TTGGACCGGAAA
TTGGACCGGAAA
1
62
4.98
1.13E−06
3′ss
Mel.



683395-685920
683380-685920
AGACTTTGAGTC
AGACTTTGATGA





TCTTTTTGCAGA
TGGATGCCAACC





TGAT (15)
AGCG (16)





536
chr1:
chr1:
ATCAGAAATTCG
ATCAGAAATTCG
0
29
4.91
8.06E−03
3′ss
Mel.



212515622-212519131
212515622-212519144
TACAACAGGTTT
TACAACAGCTCC





CTTTTAAAGCTC
TGGAGCTTTTTG





CTGG (65)
ATAG (66)





537
chr1:
chr1:
CTCAGAGCCAGG
CTCAGAGCCAGG
0
29
4.91
3.06E−05
3′ss
Mel.



35871069-35873587
35871069-35873608
CTGTAGAGATGT
CTGTAGAGTCCG





TTTCTACCTTTC
CTCTATCAAGCT





CACA (105)
GAAG (106)





538
chrX:
chrX:
GTCTTGAGAATT
ACTTCCTTAGTG
0
29
4.91
1.16E−06
5′ss
Mel.



47059943-47060292
47059013-47060292
GGAAGCAGGTGG
GTTTCCAGGTGG





TGGTGCTCACCA
TGGTGCTCACCA





ACAC (113)
ACAC (112)





539
chr2:
chr2:
AAATTTAACATT
AAATTTAACATT
0
28
4.86
3.75E−06
3′ss
Mel.



24207701-24222524
24207701-24222541
ACTCATAGTTTT
ACTCATAGAGTA





TGCTGTTTTACA
AGCCATATCAAA





GAGT (546)
GACT (547)





540
chr5:
chr5:
CTCCATGCTCAG
CTCCATGCTCAG
0
28
4.86
8.03E−04
3′ss
Mel.



869519-870587
865696-870587
CTCTCTGGTTTC
CTCTCTGGGGAA





TTTCAGGGCCTG
GGTGAAGAAGGA





CCAT (128)
GCTG (129)





541
chr20:
chr20:
ACATGAAGGTGG
ACATGAAGGTGG
0
27
4.81
4.86E−06
3′ss
Mel.



34144042-34144725
34144042-34144743
ACGGAGAGGCTC
ACGGAGAGGTAC





CCCTCCCACCCC
TGAGGACAAATC





AGGT (49)
AGTT (50)





542
chr2:
chr2:
TGGGAGGAGCAT
TGGGAGGAGCAT
0
27
4.81
1.72E−04
3′ss
Mel.



97285513-97297048
97285499-97297048
GTCAACAGAGTT
GTCAACAGGACT





TCCCTTATAGGA
GGCTGGACAATG





CTGG (9)
GCCC (10)





543
chr19:
chr19:
AGCCATTTATTT
AGCCATTTATTT
1
54
4.78
1.18E−09
3′ss
Mel.



9728842-9730107
9728855-9730107
GTCCCGTGGGAA
GTCCCGTGGGTT





CCAATCTGCCCT
TTTTTCCAGGGA





TTTG (160)
ACCA (161)





544
chr15:
chr15:
ATATTCCTTTTA
ATATTCCTTTTA
0
25
4.70
3.65E−06
3′ss
Mel.



49420970-49421673
49420957-49421673
TTTCTAAGTCTT
TTTCTAAGGAGT





TTGTCTTAGGAG
TAAACATAGATG





TTAA (864)
TAGC (865)





545
chr12:
chr12:
ATTTGGACTCGC
ATTTGGACTCGC
1
49
4.64
6.42E−06
3′ss
Mel.



105601825-105601935
105601807-105601935
TAGCAATGATGT
TAGCAATGAGCA





CTGTTTATTTTT
TGACCTCTCAAT





AGAG (41)
GGCA (42)





546
chr14:
chr14:
AGATGTCAGGTG
AGATGTCAGGTG
0
24
4.64
2.35E−03
3′ss
Mel.



75356052-75356580
75356052-75356599
GGAGAAAGCCTT
GGAGAAAGCTGT





TGATTGTCTTTT
TGGAGACACAGT





CAGC (89)
TGCA (90)





547
chr11:
chr11:
CATAAAATTCTA
CATAAAATTCTA
0
23
4.58
4.56E−05
3′ss
Mel.



4104212-4104471
4104212-4104492
ACAGCTAATTCT
ACAGCTAAGCAA





CTTTCCTCTGTC
GCACTGAGCGAG





TTCA (69)
GTGA (70)





548
chr15:
chr15:
GAAACCAACTAA
GAAACCAACTAA
0
23
4.58
2.75E−04
3′ss
Mel.



59209219-59224554
59209198-59224554
AGGCAAAGCCCA
AGGCAAAGGTAA





TTTTCCTTCTTT
AAAACATGAAGC





CGCA (101)
AGAT (102)





549
chr22:
chr22:
CTGGGAGGTGGC
CTGGGAGGTGGC
0
23
4.58
1.03E−06
3′ss
Mel.



19044699-19050714
19044675-19050714
ATTCAAAGCCCC
ATTCAAAGGCTC





ACCTTTTGTCTC
TTCAGAGGTGTT





CCCA (45)
CCTG (46)





550
chr3:
chr3:
CACTGCTGGGAG
CACTGCTGGGAG
0
23
4.58
5.29E−10
3′ss
Mel.



129284872-129285369
129284860-129285369
AGTGGAAGTTGC
AGTGGAAGATTC





TTCCACAGATTC
CTGAGAGCTGCC





CTGA (524)
GGCC (525)





551
chr9:
chr9:
GGTCCTGAACGC
GGTCCTGAACGC
0
23
4.58
1.89E−04
3′ss
Mel.



138903859-138905044
138903870-138905044
TGTGAAATAACT
TGTGAAATTGTA





TCGCCCCCAGCT
CTGTCAGAACTT





TCAA (866)
CGCC (867)





552
chr6:
chr6:
TGGAGCAGTATG
TGGAGCAGTATG
0
22
4.52
8.93E−03
3′ss
Mel.



35255622-35258029
35255622-35258042
CCAGCAAGACTT
CCAGCAAGGTTC





TTCCCCCAGGTT
TTCATGACAGCC





CTTC (868)
AGAT (869)





553
chr8:
chr8:
TCGTGCAGACCC
TCGTGCAGACCC
0
22
4.52
3.21E−11
3′ss
Mel.



28625893-28627405
28625839-28627405
TGGAGAAGATCT
TGGAGAAGCATG





CACAGATGTGCA
GCTTCAGTGATA





GTCT (870)
TTAA (871)





554
chr6:
chr6:
CCGGGGCCTTCG
CCGGGGCCTTCG
2
67
4.50
2.74E−12
3′ss
Mel.



10723474-10724788
10723474-10724802
TGAGACCGCTTG
TGAGACCGGTGC





TTTTCTGCAGGT
AGGCCTGGGGTA





GCAG (95)
GTCT (96)





555
chr4:
chr4:
GTGCCAACGAGG
GTGCCAACGAGG
2
65
4.46
9.90E−07
3′ss
Mel.



184577127-184580081
184577114-184580081
ACCAGGAGTTCT
ACCAGGAGATGG





TTATTTCAGATG
AACTAGAAGCAT





GAAC (734)
TACG (735)





556
chr22:
chr22:
CTCTCTCCAACC
CTCTCTCCAACC
0
21
4.46
4.84E−04
3′ss
Mel.



39064137-39066874
39064137-39066888
TGCATTCTCATC
TGCATTCTTTGG





TCGCCCACAGTT
ATCGATCAACCC





GGAT (140)
GGGA (141)





557
chr9:
chr9:
TTGAAGCTCAGT
TTGAAGCTCAGT
0
21
4.46
3.30E−03
3′ss
Mel.



37501841-37503015
37501841-37503039
GAGAAAAGTTCT
GAGAAAAGGATG





TCTGTTTATGTC
ATGGAGATAGCC





TTCC (872)
AAAG (873)





558
chr14:
chr14:
CAGTTATAAACT
CAGTTATAAACT
0
20
4.39
2.55E−03
3′ss
Mel.



71059726-71060012
71059705-71060012
CTAGAGTGAGTT
CTAGAGTGCTTA





TATTTTCCTTTT
CTGCAGTGCATG





ACAA (79)
GTAT (80)





559
chr17:
chr17:
GGAGCAGTGCAG
GGAGCAGTGCAG
0
20
4.39
2.74E−12
3′ss
Mel.



71198039-71199162
71198039-71199138
TTGTGAAATCAT
TTGTGAAAGTTT





TACTTCTAGATG
TGATTCATGGAT





ATGC (31)
TCAC (32)





560
chr9:
chr9:
CGCCCTGACACA
CGCCCTGACACA
0
20
4.39
1.26E−04
3′ss
Mel.



35608506-35608842
35608506-35608858
CAATCAGGACTT
CAATCAGGGCTC





CTCTATCTACAG
TGTTGCAAGAGG





GCTC (874)
GGGT (875)





561
chrX:
chrX:
ACTTCCTTAGTG
ACTTCCTTAGTG
0
20
4.39
2.32E−03
3′ss
Mel.



47059013-47059808
47059013-47060292
GTTTCCAGGTTG
GTTTCCAGGTGG





CCAGGGCACTGC
TGGTGCTCACCA





AGCT (111)
ACAC (112)





562
chr12:
chr12:
CTTGGAGCTGAC
CTTGGAGCTGAC
4
96
4.28
5.10E−13
3′ss
Mel.



107378993-107380746
107379003-107380746
GCCGACGGGGAA
GCCGACGGTTTA





CTGACAAGATCA
TTGCAGGGAACT





CATT (130)
GACA (131)





563
chr10:
chr10:
TTGCTGGCCATC
TTGCTGGCCATC
0
18
4.25
1.13E−14
3′ss
Mel.



133782836-133784141
133782073-133784141
GGATTGGGCCCT
GGATTGGGGATC





TCGTTTCAGGAT
TATATTGGAAGG





GGAT (876)
CGTC (877)





564
chr11:
chr11:
CCACCGCCATCG
CCACCGCCATCG
0
18
4.25
6.04E−04
3′ss
Mel.



64877395-64877934
64877395-64877953
ACGTGCAGTACC
ACGTGCAGGTGG





TCTTTTTACCAC
GGCTCCTGTACG





CAGG (167)
AAGA (168)





565
chr21:
chr21:
ATCATAGCCCAC
ATCATAGCCCAC
1
35
4.17
1.72E−04
3′ss
Mel.



37416267-37417879
37416254-37417879
ATGTCCAGTTTT
ATGTCCAGGTAA





TCTTTCTAGGTA
AAGCAGCGTTTA





AAAG (695)
ATGA (696)





566
chr15:
chr15:
TGATTCCAAGCA
TGATTCCAAGCA
1
34
4.13
1.03E−06
3′ss
Mel.



25213229-25219533
25213229-25219457
AAAACCAGCCTT
AAAACCAGGCTC





CCCCTAGGTCTT
CATCTACTCTTT





CAGA (230)
GAAG (231)





567
chr17:
chr17:
TACTGAAATGTG
TACTGAAATGTG
0
16
4.09
5.46E−04
3′ss
Mel.



34942628-34943454
34942628-34943426
ATGAACATATCC
ATGAACATATCC





AGGTAATCGAGA
AGAAGCTTGGAA





GACC (124)
GCTG (125)





568
chr2:
chr2:
CCATTCGAGAGC
CCATTCGAGAGC
0
16
4.09
2.25E−03
3′ss
Mel.



219610954-219611752
219610954-219611725
ATCAGAAGATTG
ATCAGAAGCTAA





GGAGGAAGGACC
ACCATTTCCCAG





GGCT (878)
GCTC (879)





569
chr10:
chr10:
TCTTGCCAGAGC
TCTTGCCAGAGC
0
15
4.00
9.94E−07
3′ss
Mel.



99219232-99219415
99219283-99219415
TGCCCACGCTCT
TGCCCACGCTTC





CCACCCTCAGCT
TTTCCTTGCTGC





GCCT (587)
TGGA (588)





570
chr11:
chr11:
AGATCGCCTGGC
AGATCGCCTGGC
0
15
4.00
9.65E−05
3′ss
Mel.



3697619-3697738
3697606-3697738
TCAGTCAGTTTT
TCAGTCAGACAT





TCTCTCTAGACA
GGCCAAACGTGT





TGGC (187)
AGCC (188)





571
chr11:
chr11:
CGGCGCGGGCAA
CGGCGCGGGCAA
0
15
4.00
4.00E−05
3′ss
Mel.



62648919-62649352
62648919-62649364
CCTGGCGGCCCC
CCTGGCGGGTCT





CATTTCAGGTCT
GAAGGGGCGTCT





GAAG (165)
CGAT (166)





572
chr1:
chr1:
TCAGGAGCAGAG
CTCAGGGAAGGG
0
15
4.00
2.96E−02
5′ss
Mel.



113195986-113196219
113192091-113196219
AGGAAAAGTGCA
GCAGCACATGCA





TTTGCCCAGTAT
TTTGCCCAGTAT





AACA (880)
AACA (881)





573
chr1:
chr1:
CGATCTCCCAAA
CGATCTCCCAAA
0
15
4.00
5.55E−03
3′ss
Mel.



52880319-52880412
52880319-52880433
AGGAGAAGTCTG
AGGAGAAGCCCC





ACCAGTCTTTTC
TCCCCTCGCCGA





TACA (55)
GAAA (56)





574
chr15:
chr15:
TCACACAGGATA
GCCTCACTGAGC
1
30
3.95
6.03E−06
exon
Mel.



25212299-25213078
25207356-25213078
ATTTGAAAGTGT
AACCAAGAGTGT




incl.





CAGTTGTACCCG
CAGTTGTACCCG





AGGC (164)
AGGC (145)





575
chr11:
chr11:
TGCAGCTGGCCC
TGCAGCTGGCCC
0
14
3.91
1.39E−07
3′ss
Mel.



64002365-64002911
64002365-64002929
CCGCCCAGGTCT
CCGCCCAGGCCC





TTTCTCTCCCAC
CTGTCTCCCAGC





AGGC (638)
CTGA (639)





576
chr12:
chr12:
GCCTGCCTTTGA
GCCTGCCTTTGA
0
14
3.91
1.83E−03
3′ss
Mel.



113346629-113348840
113346629-113348855
TGCCCTGGATTT
TGCCCTGGGTCA





TGCCCGAACAGG
GTTGACTGGCGG





TCAG (71)
CTAT (72)





577
chr17:
chr17:
CCAAGCTGGTGT
CCAAGCTGGTGT
0
14
3.91
1.08E−03
3′ss
Mel.



78188582-78188831
78188564-78188831
GCGCACAGGCCT
GCGCACAGGCAT





CTCTTCCCGCCC
CATCGGGAAGAA





AGGC (73)
GCAC (74)





578
chr2:
chr2:
GTGTGGCAAGTA
GTGTGGCAAGTA
0
14
3.91
1.45E−02
3′ss
Mel.



85848702-85850728
85848702-85850768
CTTTCAAGTATC
CTTTCAAGGCCG





TGCCCTTCTATT
GGGTTTGAAGTC





ACAG (882)
TCAC (883)





579
chr12:
chr12:
AAAATCATTGAT
AAAATCATTGAT
0
13
3.81
1.44E−03
3′ss
Mel.



29450133-29460566
29450133-29460590
TCCCTTGAAATT
TCCCTTGAGTGG





CTCTTTACTCTA
TTAGACGATGCT





CCTT (884)
ATTA (885)





580
chr14:
chr14:
GTGGGGGGCCAT
GTGGGGGGCCAT
0
13
3.81
2.75E−04
3′ss
Mel.



23237380-23238985
23237380-23238999
TGCTGCATTTTG
TGCTGCATGTAC





TATTTTCCAGGT
AGTCTTTGCCCG





ACAG (122)
CTGC (123)





581
chr22:
chr22:
CGCTGGCACCAT
CGCTGGCACCAT
0
13
3.81
5.09E−08
3′ss
Mel.



36627480-36629198
36627512-36629198
GAACCCAGTATT
GAACCCAGAGAG





TCCAGGACCAAG
CAGTATCTTTAT





TGAG (199)
TGAG (200)





582
chr19:
chr19:
TGCCTGTGGACA
TGCCTGTGGACA
0
12
3.70
4.53E−04
3′ss
Mel.



14031735-14034130
14031735-14034145
TCACCAAGCCTC
TCACCAAGGTGC





GTCCTCCCCAGG
CGCCTGCCCCTG





TGCC (59)
TCAA (60)





583
chr20:
chr20:
TTTGCAGGGAAT
TTTGCAGGGAAT
0
12
3.70
9.65E−05
3′ss
Mel.



35282126-35284762
35282104-35284762
GGGCTACATCCC
GGGCTACATACC





CTTGGTTCTCTG
ATCTGCCAGCAT





TTAC (35)
GACT (36)





584
chr22:
chr22:
TGCTCAGAGGTG
TGCTCAGAGGTG
0
12
3.70
8.43E−07
3′ss
Mel.



19948812-19950181
19948812-19950049
CTTTGAAGCCCA
CTTTGAAGATGC





TCCACAACCTGC
CGGAGGCCCCGC





TCAT (886)
CTCT (887)





585
chr2:
chr2:
CAAGATAGATAT
CAAGATAGATAT
0
12
3.70
3.94E−03
3′ss
Mel.



170669034-170671986
170669016-170671986
TATAGCAGGTGG
TATAGCAGAACT





CTTTTGTTTTAC
TCGATATGACCT





AGAA (99)
GCCA (100)





586
chr15:
chr15:
GCCTCACTGAGC
GCCTCACTGAGC
2
37
3.66
8.44E−08
exon
Mel.



25207356-25212175
25207356-25213078
AACCAAGAGTAG
AACCAAGAGTGT




incl.





TGACTTGTCAGG
CAGTTGTACCCG





AGGA (144)
AGGC (145)





587
chr11:
chr11:
CCACGGCCACGG
CCACGGCCACGG
4
60
3.61
3.80E−03
3′ss
Mel.



8704812-8705536
8704812-8705552
CCGCATAGCTTT
CCGCATAGGCAA





GTATTCCTGCAG
GCACCGGAAGCA





GCAA (888)
CCCC (889)





588
chr11:
chr11:
CATGCCGGGGCC
CATGCCGGGGCC
0
11
3.58
1.83E−02
3′ss
Mel.



11988666-11989941
11988645-11989941
AGAGGATGGCTC
AGAGGATGCTCT





TTTCCACCTGTC
GCACCCGGGACA





TGCA (890)
GTGA (891)





589
chr16:
chr16:
GGCCAAGCAAGA
GGCCAAGCAAGA
0
11
3.58
1.88E−02
3′ss
Mel.



19838459-19843229
19838459-19867808
ACAAAAAGTATT
ACAAAAAGTGAA





TTCTTCTAGGAT
ATGCAAAATGGA





GGAA (892)
GGAC (893)





590
chr1:
chr1:
GGCTCCCATTCT
GGCTCCCATTCT
0
11
3.58
2.42E−03
3′ss
Mel.



155630724-155631097
155630704-155631097
GGTTAAAGAGTG
GGTTAAAGGCCA





TTCTCATTTCCA
GTCTGCCATCCA





ATAG (195)
TCCA (196)





591
chr1:
chr1:
GAAGAACAGGAT
GAAGAACAGGAT
0
11
3.58
1.74E−02
3′ss
Mel.



219366593-219383856
219366593-219383873
ATTAATAGTATG
ATTAATAGGAGG





TTTTTGTTTTTA
ATTCTCTATGGG





GGAG (894)
AGGA (895)





592
chr19:
chr19:
CAAGCAGGTCCA
CAAGCAGGTCCA
0
10
3.46
2.28E−04
3′ss
Mel.



5595521-5598803
5595508-5598803
AAGAGAGATTTT
AAGAGAGAAGCT





GGTAAACAGAGC
CCAAGAGTCAGG





TCCA (138)
ATCG (139)





593
chr5:
chr5:
CAATTCAGTAGA
AGGTCTTCCTGG
0
10
3.46
2.42E−02
5′ss
Mel.



462644-464404
462422-464404
TTCACCCTCAAC
ACCTGGAGCAAC





ATCTGAATGAAT
ATCTGAATGAAT





TGAT (896)
TGAT (897)





594
chr9:
chr9:
GGGAGATGGATA
GGGAGATGGATA
3
41
3.39
1.97E−10
3′ss
Mel.



35813153-35813262
35813142-35813262
CCGACTTGCTCA
CCGACTTGTGAT





ATTTCAGTGATC
CAACGATGGGAA





AACG (146)
GCTG (147)





595
chr1:
chr1:
AGAGGGCACGGG
AGAGGGCACGGG
2
29
3.32
1.42E−03
3′ss
Mel.



205240383-205240923
205240383-205240940
ACATCCAGCCCC
ACATCCAGGAGG





TCTGCCCCTGCA
CCGTGGAGTCCT





GGAG (898)
GCCT (899)





596
chr11:
chr11:
TTCTCCAGGACC
TTCTCCAGGACC
0
9
3.32
6.24E−03
3′ss
Mel.



125442465-125445146
125442465-125445158
TTGCCAGACCTT
TTGCCAGAGGAA





TTCTATAGGGAA
TCAAAGACTCCA





TCAA (150)
TCTG (151)





597
chr11:
chr11:
GGATGACCGGGA
GGATGACCGGGA
0
9
3.32
3.79E−04
3′ss
Mel.



71939542-71939690
71939542-71939770
TGCCTCAGTCAC
TGCCTCAGATGG





TTTACAGCTGCA
GGAGGATGAGAA





TCGT (47)
GCCC (48)





598
chr16:
chr16:
AGATGATTGAGG
AGATGATTGAGG
0
9
3.32
1.06E−02
3′ss
Mel.



70292147-70292882
70292120-70292882
CAGCCAAGCTCT
CAGCCAAGGCCG





TTTCTGTCTTCT
TCTATACCCAGG





TGGT (900)
ATTG (901)





599
chr2:
chr2:
GAGGAGCCACAC
GAGGAGCCACAC
0
9
3.32
2.20E−02
3′ss
Mel.



220044485-220044888
220044485-220044831
TCTGACAGATAC
TCTGACAGTGAG





CTGGCTGAGAGC
GGTGCGGGGTCA





TGGC (107)
GGCG (108)





600
chr3:
chr3:
GCTGCTCTCTTC
GCTGCTCTCTTC
0
9
3.32
2.87E−06
3′ss
Mel.



45043100-45046767
45043100-45046782
AATACAAGTGCT
AATACAAGGATA





TCTGCTTCCAGG
CCAAGGGTTCGA





ATAC (902)
GTTT (903)





601
chr9:
chr9:
AATAGAACTTCC
AATAGAACTTCC
7
76
3.27
4.47E−08
3′ss
Mel.



101891382-101894778
101891382-101894790
AACTACTGGCCC
AACTACTGTAAA





TTTTTCAGTAAA
GTCATCACCTGG





GTCA (904)
CCTT (905)





602
chr17:
chr17:
CTATTTCACTCT
CTATTTCACTCT
2
27
3.22
1.02E−05
3′ss
Mel.



7131030-7131295
7131102-7131295
CCCCCGAACCTA
CCCCCGAAATGA





TCCAGGTTCCTC
GCCCATCCAGCC





CTCC (33)
AATT (34)





603
chr17:
chr17:
TGTTACTGCAGT
TGTTACTGCAGT
1
17
3.17
2.33E−03
3′ss
Mel.



79556145-79563141
79556130-79563141
GGCTACAGGTCT
GGCTACAGGTGG





CTCTCTTGCAGG
TCCTGACAACCA





TGGT (906)
AGTC (907)





604
chr13:
chr13:
ACATCACAAAGC
ACATCACAAAGC
0
8
3.17
1.95E−03
3′ss
Mel.



45841511-45857556
45841511-45857576
AACCTGTGGGGT
AACCTGTGGTGT





TTTGTTTTTGTT
ACCTGAAGGAAA





TTAG (908)
TCTT (909)





605
chr14:
chr14:
GGTGCTGGCTGC
GGTGCTGGCTGC
0
8
3.17
3.94E−03
3′ss
Mel.



105176525-105177255
105176525-105177273
CTGCGAAACCCT
CTGCGAAAGCCT





GGCTGCCCCTGC
GCTCACCAGCCG





AGGC (910)
CCAG (911)





606
chr16:
chr16:
CACCAAGCAGAG
CACCAAGCAGAG
0
8
3.17
7.87E−04
3′ss
Mel.



15129410-15129852
15129410-15129872
GCTTCCAGTCTG
GCTTCCAGGCCA





TCTGCCCTTTCT
GAAGCCTTTTAA





GTAG (216)
AAGG (217)





607
chr17:
chr17:
CCTCTCTGCTCG
CCTCTCTGCTCG
0
8
3.17
7.21E−08
3′ss
Mel.



17062316-17064532
17062316-17064553
AGAAGGAGTGTG
AGAAGGAGCTGG





TGTCTTTTTGCC
AGCAGAGCCAGA





AACA (912)
AGGA (913)





608
chr19:
chr19:
ATCACAACCGGA
ATCACAACCGGA
0
8
3.17
1.45E−02
3′ss
Mel.



15491444-15507960
15491423-15507960
ACCGCAGGCTCC
ACCGCAGGCTCA





TTCTGCCCTGCC
TGATGGAGCAGT





CGCA (661)
CCAA (662)





609
chr3:
chr3:
CTGGAAGCTCAA
CTGGAAGCTCAA
0
8
3.17
4.68E−04
3′ss
Mel.



112724877-112727017
112724851-112727017
GGTACTAGATTT
GGTACTAGTTTG





TTCCTCTCTCTG
CCAAAGAAACTA





TCTT (914)
GAGT (915)





610
chr1:
chr1:
CCCGAGCTCAGA
CCCGAGCTCAGA
4
41
3.07
3.31E−04
3′ss
Mel.



3548881-3549961
3548902-3549961
GAGTAAATTCTC
GAGTAAATATGA





CTTACAGACACT
GATCGCCTCTGT





GAAA (177)
CCCA (178)





611
chr2:
chr2:
TATCCATTCCTG
TATCCATTCCTG
1
15
3.00
3.44E−05
3′ss
Mel.



178096758-178097119
178096736-178097119
AGTTACAGTATA
AGTTACAGTGTC





AACTTCCTTCTC
TTAATATTGAAA





ATGC (156)
ATGA (157)





612
chr11:
chr11:
CGGCGATGACTC
CGGCGATGACTC
0
7
3.00
2.48E−02
3′ss
Mel.



62554999-62556481
62554999-62556494
GGACCCAGCTTC
GGACCCAGGGCT





TCTCCACAGGGC
CCTTCAGTGGTA





TCCT (916)
GATG (917)





613
chr15:
chr15:
CCGCCAGGAGAA
CCGCCAGGAGAA
0
7
3.00
9.38E−04
3′ss
Mel.



41102168-41102274
41102168-41102268
CAAGCCCATCCC
CAAGCCCAAGTT





CTCACAGGCAGA
AGTCCCCTCACA





GATA (918)
GGCA (919)





614
chr16:
chr16:
CAGCAGCAGCTC
CAGCAGCAGCTC
0
7
3.00
9.09E−03
3′ss
Mel.



48311390-48330007
48311390-48329925
TGCTTGAGCTAC
TGCTTGAGGTGT





TGCCAACACCAC
TGGATCCTGAAC





TGCT (920)
AAAA (921)





615
chr2:
chr2:
AGACAAGGGATT
AGACAAGGGATT
0
7
3.00
6.35E−04
3′ss
Mel.



26437445-26437921
26437430-26437921
GGTGGAAACATT
GGTGGAAAAATT





TTATTTTACAGA
GACAGCGTATGC





ATTG (295)
CATG (296)





616
chr3:
chr3:
GCACTTATGGTG
GCACTTATGGTG
0
7
3.00
1.74E−07
3′ss
Mel.



48638222-48638407
48638273-48638407
GTGGCGTGAGTT
GTGGCGTGCACC





TCCAGACCTTCA
TGTCCAGCCCAC





GCAT (922)
TGGC (923)





617
chr19:
chr19:
GTGCTTGGAGCC
GTGCTTGGAGCC
4
35
2.85
1.91E−07
3′ss
Mel.



55776746-55777253
55776757-55777253
CTGTGCAGACTT
CTGTGCAGCCTG





TCCGCAGGGTGT
GTGACAGACTTT





GCGC (179)
CCGC (180)





618
chr9:
chr9:
GTGGCTCCAGTA
GACCTGCTCAAG
8
63
2.83
2.74E−02
5′ss
Mel.



119414072-119488049
119414072-119449344
TCAGAAAGAGAC
TTCACTCAAGAC





CACAGAGCTGGG
CACAGAGCTGGG





CAGC (924)
CAGC (925)





619
chr10:
chr10:
TGTGGGCATGGA
TGTGGGCATGGA
0
6
2.81
8.27E−08
3′ss
Mel.



82264534-82266954
82264534-82266983
GCGAAAAGTGCT
GCGAAAAGGGTG





GCCCTGCTTTCT
TGCTGTCCGACC





CTGT (926)
TCAC (927)





620
chr12:
chr12:
TTCCTCTTCCCC
TTCCTCTTCCCC
0
6
2.81
4.32E−06
3′ss
Mel.



56361953-56362539
56361953-56362561
TCATCAAGTCCT
TCATCAAGAGCT





CTCTTTCTCCTT
ATCTGTTCCAGC





TGTC (928)
TGCT (929)





621
chr19:
chr19:
GGGGCACTGACA
GGGGCACTGACA
0
6
2.81
2.67E−02
3′ss
Mel.



50149459-50149761
50149459-50149782
CGGCTACTAGCC
CGGCTACTGTGT





TCTCTGGCCTCT
TGGACATGGCCA





TCCA (930)
CGGA (931)





622
chr20:
chr20:
ACATGAAGGTGG
ACATGAAGGTGG
0
6
2.81
1.25E−04
3′ss
Mel.



34144042-34144761
34144042-34144743
ACGGAGAGTTCT
ACGGAGAGGTAC





CTGTGACCAGAC
TGAGGACAAATC





ATGA (250)
AGTT (50)





623
chrX:
chrX:
TGACTCCGCTGC
TGACTCCGCTGC
0
6
2.81
1.80E−02
3′ss
Mel.



118923962-118925536
118923974-118925536
TCGCCATGACTT
TCGCCATGTCTT





TCAGGATTAAGC
CTCACAAGACTT





GATT (697)
TCAG (698)





624
chr2:
chr2:
CCCCTGAGATGA
CCCCTGAGATGA
3
25
2.70
6.46E−06
exon
Mel.



27260570-27260682
27260570-27261013
AGAAAGAGCTCC
AGAAAGAGCTCC




incl.





CTGTTGACAGCT
TGAGCAGCCTGA





GCCT (183)
CTGA (184)





625
chr2:
chr2:
AGGCTGTAGCAG
AGGCTGTAGCAG
1
12
2.70
2.24E−02
3′ss
Mel.



99225189-99226105
99225189-99226218
GACTCCAGGGTT
GACTCCAGGAAG





GGGAAGAACATG
ATGTTACCGAGT





GAAA (932)
ACTT (933)





626
chr8:
chr8:
CCGAGGATGCTA
CCGAGGATGCTA
4
30
2.63
6.42E−03
3′ss
Mel.



133811106-133811328
133811106-133816063
AGGGGCAGTTTC
AGGGGCAGGATT





TGTTCCAGGTGA
GGATAGCTTTAG





AATC (934)
TCAA (935)





627
chr21:
chr21:
GCCTCCCGGTCC
GCCTCCCGGTCC
4
29
2.58
9.60E−04
3′ss
Mel.



46935066-46945730
46936054-46945730
GCAAGCAGAATG
GCAAGCAGTTCC





AAGAACTGCATG
AGTTATACTCCG





TGGC (936)
TGTA (937)





628
chr17:
chr17:
TCGTAACAGGGG
CTGTGACGGGTG
3
23
2.58
1.22E−02
exon
Mel.



27210249-27212874
27210249-27211242
TTGCACAGGTGA
TCGCCCAGGTGA




skip





AGATCATGACGG
AGATCATGACGG





AGAA (938)
AGAA (939)





629
chr6:
chr6:
GTTTGGGGAAGT
GTTTGGGGAAGT
1
11
2.58
2.07E−05
exon
Mel.



112020873-112021306
112017659-112021306
ATGGATGGAGAA
ATGGATGGGTAC




incl.





AGCTGATGGTTT
CTGGAATGGAAA





GTGT (940)
CACA (941)





630
chr6:
chr6:
TAACTAATCCTT
CAGCCTACCAGA
1
11
2.58
4.06E−02
5′ss
Mel.



39854223-39855261
39851845-39855261
CTCAGCAGAAAG
GGCACCAGAAAG





AGCTGGGCTCCA
AGCTGGGCTCCA





CTGA (942)
CTGA (943)





631
chr11:
chr11:
AGTCCAGCCCCA
AGTCCAGCCCCA
0
5
2.58
9.35E−03
3′ss
Mel.



64900740-64900940
64900723-64900940
GCATGGCACCTC
GCATGGCAGTCC





TCCCCACTCCTA
TGTACATCCAGG





GGTC (136)
CCTT (137)





632
chr16:
chr16:
GGATCCTTCACC
GGATCCTTCACC
0
5
2.58
1.87E−03
3′ss
Mel.



1402307-1411686
1402307-1411743
CGTGTCTGTCTT
CGTGTCTGGACC





TGCAGACAGGTT
CGTGCATCTCTT





CTGT (85)
CCGA (86)





633
chr17:
chr17:
GCATCTCAGCCC
GCATCTCAGCCC
0
5
2.58
1.16E−05
3′ss
Mel.



16344444-16344670
16344444-16344681
AAGAGAAGTTTC
AAGAGAAGGTTA





TTTGCAGGTTAT
TATTCCCAGAGG





ATTC (287)
ATGT (288)





634
chr1:
chr1:
CTACACAGAGCT
CTACACAGAGCT
0
5
2.58
2.48E−06
3′ss
Mel.



32096333-32098095
32096443-32098095
GCAGCAAGGTGT
GCAGCAAGCTCT





GCACCCAGCTGC
GTCCCAAATGGG





AGGT (291)
CTAC (292)





635
chr22:
chr22:
CCTGCGCAACTG
CCTGCGCAACTG
0
5
2.58
1.56E−04
3′ss
Mel.



19164146-19164358
19164206-19164358
GTACCGAGGCGC
GTACCGAGGGGA





AGCCAGTGTCTT
CAACCCCAACAA





TGGA (944)
GCCC (945)





636
chr3:
chr3:
ATAAAAATTGCT
ATAAAAATTGCT
0
5
2.58
2.28E−03
3′ss
Mel.



131181737-131186934
131181719-131186934
TAGTAAAGATTT
TAGTAAAGGTCA





TTGCCTTCTCTC
AAGATTCTAAAC





AGGT (946)
TGCC (947)





637
chr8:
chr8:
TGAGTTCATGGA
TGAGTTCATGGA
0
5
2.58
3.48E−02
3′ss
Mel.



98817692-98827531
98817692-98827555
TGATGCCAAAAT
TGATGCCAACAT





TCTTTTTAATCT
GTGCATTGCCAT





TTCG (948)
TGCG (949)





638
chrX:
chrX:
AGAGTTGAAAAA
AGAGTTGAAAAA
0
5
2.58
4.97E−03
3′ss
Mel.



24091380-24092454
24091380-24094838
CACTGGCGTCTC
CACTGGCGTTTA





CTTTTCAGGAAT
ATTGGTTGGGGT





CACA (950)
CAGA (951)





639
chr12:
chr12:
GGCCAGCCCCCT
GGCCAGCCCCCT
8
51
2.53
3.07E−09
3′ss
Mel.



120934019-120934204
120934019-120934218
TCTCCACGGCCT
TCTCCACGGTAA





TGCCCACTAGGT
CCATGTGCGACC





AACC (206)
GAAA (207)





640
chr9:
chr9:
CACCACGCCGAG
CACCACGCCGAG
3
21
2.46
2.87E−02
3′ss
Mel.



125023777-125026993
125023787-125026993
GCCACGAGACAT
GCCACGAGTATT





TGATGGAAGCAG
TCATAGACATTG





AAAC (142)
ATGG (143)





641
chr10:
chr10:
TGGGGCCACAAA
TGGGGCCACAAA
4
24
2.32
1.77E−02
exon
Mel.



74994698-74999069
74994698-74994950
GACAGATGCTGG
GACAGATGAAAC




skip





ATACACAGTATC
CCCATGGCGACT





GTCG (952)
CTAG (953)





642
chr1:
chr1:
CTTGCCTTCCCA
CTTGCCTTCCCA
1
9
2.32
1.49E−04
3′ss
Mel.



154246074-154246225
154246074-154246249
TCCTCCTGCAAA
TCCTCCTGAACT





CACCTGCCACCT
TCCAGGTCCTGA





TTCT (289)
GTCA (290)





643
chr11:
chr11:
GGGGACAGTGAA
GGGGACAGTGAA
0
4
2.32
1.19E−05
3′ss
Mel.



57100545-57100908
57100623-57100908
ATTTGGTGGCAA
ATTTGGTGGGCA





GAATGAGGTGAC
GCTGCTTTCCTT





ACTG (103)
TGAC (104)





644
chr16:
chr16:
GAACTGGCACCG
GAACTGGCACCG
0
4
2.32
1.03E−03
3′ss
Mel.



313774-313996
313774-314014
ACAGACAGTGTC
ACAGACAGATCC





CCCTCCCTCCCC
TGTTTCTGGACC





AGAT (244)
TTGG (245)





645
chr17:
chr17:
AACATGGAATCA
AACATGGAATCA
0
4
2.32
1.03E−03
3′ss
Mel.



34147441-34149625
34147441-34149643
TCAGGAAGTTCT
TCAGGAAGCCAA





CCATTTCTATTT
GGTGGAAGAGCA





AGCC (954)
CCTT (955)





646
chr1:
chr1:
CGTGCGTGTGTG
CTTAGGAAAGAC
0
4
2.32
2.87E−02
5′ss
Mel.



1480382-1497319
1480382-1500152
TGCTCTTGCTAT
AAAGAACTCTAT





ACACAGAATGGG
ACACAGAATGGG





ATTT (956)
ATTT (957)





647
chr22:
chr22:
CCCAGCCTGCTG
CCCAGCCTGCTG
0
4
2.32
3.33E−02
3′ss
Mel.



24108483-24109560
24108462-24109560
TCCAGCAGCCTC
TCCAGCAGGCCC





TTGCACTGTACC
CCACCCCCGCTG





CCCA (958)
CCCC (959)





648
chr22:
chr22:
ACCCAAGGCTCG
ACCCAAGGCTCG
0
4
2.32
5.75E−03
3′ss
Mel.



44559810-44564460
44559810-44564481
TCCTGAAGTTTC
TCCTGAAGACGT





TCTGTTTCCTTC
GGTTAACTTGGA





TGCA (960)
CCTC (961)





649
chr5:
chr5:
AGATTGAAGCTA
AGATTGAAGCTA
0
4
2.32
1.38E−03
3′ss
Mel.



132439718-132439902
132439718-132439924
AAATTAAGTTTT
AAATTAAGGAGC





CTGTCTTACCCA
TGACAAGTACTT





TTCC (348)
GTAG (349)





650
chr5:
chr5:
GAACCCGGTGGT
GAACCCGGTGGT
0
4
2.32
5.33E−04
3′ss
Mel.



175815974-175816311
175815974-175816331
ACCCATAGTTGC
ACCCATAGGTTG





TTTGTCCCCTCC
CCTGGCCACGGC





TCAG (962)
GGCC (963)





651
chr7:
chr7:
AATGGAAGTACC
AATGGAAGTACC
0
4
2.32
7.50E−03
3′ss
Mel.



74131270-74133179
74131270-74133197
AGCAGAAGAATT
AGCAGAAGATTC





TTATTTTTTTCA
TACTCAACATGT





AGAT (964)
CCCT (965)





652
chr20:
chr20:
GGCAGCTGTTAG
GGCAGCTGTTAG
7
37
2.25
4.91E−02
exon
Mel.



57227143-57234678
57227143-57242545
CCGAGCAAGAGC
CCGAGCAACTTG




incl.





TGGACGAGGTAT
CTGATGACCGTA





TGTG (966)
TGGC (967)





653
chr16:
chr16:
GAGATTCTGAAG
GAGATTCTGAAG
3
18
2.25
1.03E−03
3′ss
Mel.



54954250-54957496
54954322-54957496
ATAAGGAGTTCT
ATAAGGAGGTAA





CTTGTAGGATGC
AACCTGTTTAGA





CACT (313)
AATT (314)





654
chrX:
chrX:
AAAAGAAACTGA
AAAAGAAACTGA
14
70
2.24
5.98E−06
3′ss
Mel.



129771378-129790554
129771384-129790554
GGAATCAGTATC
GGAATCAGCCTT





ACAGGCAGAAGC
AGTATCACAGGC





TCTG (303)
AGAA (304)





655
chr13:
chr13:
GTTTAGAAATGG
GTTTAGAAATGG
18
88
2.23
1.12E−04
3′ss
Mel.



45911538-45912794
45911523-45912794
AAAAATGTTTTT
AAAAATGTTAAC





TGCTTTTACAGT
AAATGTGGCAAT





AACA (968)
TATT (969)





656
chr2:
chr2:
CCAAGAGACAGC
CCCCTGAGATGA
5
27
2.22
4.64E−05
exon
Mel.



27260760-27261013
27260570-27261013
ACATTCAGCTCC
AGAAAGAGCTCC




incl.





TGAGCAGCCTGA
TGAGCAGCCTGA





CTGA (315)
CTGA (184)





657
chr1:
chr1:
TTGGAAGCGAAT
TTGGAAGCGAAT
1
8
2.17
6.85E−03
3′ss
Mel.



23398690-23399766
23398690-23399784
CCCCCAAGTCCT
CCCCCAAGTGAT





TTGTTCTTTTGC
GTATATCTCTCA





AGTG (210)
TCAA (211)





658
chr6:
chr6:
AGGATGTGGCTG
AGGATGTGGCTG
1
8
2.17
2.70E−05
3′ss
Mel.



31602334-31602574
31602334-31602529
GCACAGAAGTGT
GCACAGAAATGA





CATCAGGTCCCT
GTCAGTCTGACA





GCAG (148)
GTGG (149)





659
chr3:
chr3:
AAATCTCGTGGA
AAATCTCGTGGA
7
33
2.09
4.05E−02
3′ss
Mel.



16310782-16312435
16310782-16312451
CTTCTAAGTTTT
CTTCTAAGAAAG





CTGTTTGCCCAG
CGCCATGGCCTG





AAAG (970)
TGCT (971)





660
chr11:
chr11:
AGTTCCGGGGCT
AGTTCCGGGGCT
0
3
2.00
2.75E−02
3′ss
Mel.



68838888-68839375
68838888-68839390
ACCTGATGCCTT
ACCTGATGAAAT





CCTCTTTGCAGA
CTCTCCAGACCT





AATC (972)
CGCT (973)





661
chr12:
chr12:
GGCACCCCAAAA
GGCACCCCAAAA
0
3
2.00
1.12E−02
3′ss
Mel.



58109976-58110164
58109976-58110194
GATGGCAGATCA
GATGGCAGGTGC





GTCTCTCCCTGT
GAGCCCGACCAA





TCTC (285)
GGAT (286)





662
chr1:
chr1:
AAGAAGGAATCC
AAGAAGGAATCC
0
3
2.00
7.34E−03
3′ss
Mel.



32377442-32381495
32377427-32381495
ACGTTCTAGTCA
ACGTTCTAGATT





TTTCTTTTCAGG
GGCCATTTGATG





ATTG (974)
ATGG (975)





663
chr22:
chr22:
CGCTGGCACCAT
CGCTGGCACCAT
0
3
2.00
2.55E−02
3′ss
Mel.



36627471-36629198
36627512-36629198
GAACCCAGGACC
GAACCCAGAGAG





AAGTGAGCAGAG
CAGTATCTTTAT





AGAA (976)
TGAG (200)





664
chr3:
chr3:
GCAACCAGTTTG
GCAACCAGTTTG
0
3
2.00
3.20E−03
3′ss
Mel.



49395199-49395459
49395180-49395459
GGCATCAGCTGC
GGCATCAGGAGA





CCTTCTCTCCTG
ACGCCAAGAACG





TAGG (342)
AAGA (343)





665
chr6:
chr6:
AGCCCCTGCTTG
AGCCCCTGCTTG
0
3
2.00
4.68E−04
3′ss
Mel.



170844509-170846321
170844493-170846321
ACAACCAGTTTC
ACAACCAGGTTG





ATGTCCCACCAG
GTTTTAAGAACA





GTTG (977)
TGCA (978)





666
chr9:
chr9:
CCAAGGACTGCA
CCAAGGACTGCA
0
3
2.00
4.46E−02
3′ss
Mel.



139837449-139837800
139837395-139837800
CTGTGAAGGCCC
CTGTGAAGATCT





CCGCCCCGCGAC
GGAGCAACGACC





CTGG (175)
TGAC (176)





667
chr10:
chr10:
TTGGCTGTAGGA
TTGGCTGTAGGA
8
34
1.96
2.70E−05
exon
Mel.



103904064-103908128
103904064-103904776
AACTCAGGGTCC
AACTCAGGCGGC




skip





AGCTGTAGTTCC
GTTGACATTCCC





TCTG (979)
CAGG (980)





668
chr17:
chr17:
TGTATCTCCGAC
TGTATCTCCGAC
6
26
1.95
3.79E−02
exon
Mel.



27212965-27215962
27211333-27215962
ACTCAGAGACTG
ACTCAGAGGATT




incl.





TCTCTGGAGGTT
TCCCTAGAGATT





ATGA (981)
ATGA (982)





669
chrX:
chrX:
AGGCTGATCTAC
AGGCTGATCTAC
2
10
1.87
5.30E−03
3′ss
Mel.



15849691-15863501
15845495-15863501
TGCAGGAGCCAC
TGCAGGAGGAAG





GTCATGAATATT
CTGAAACCCCAC





TTAA (983)
GTAG (984)





670
chr2:
chr2:
GGAAATGGGACA
GGAAATGGGACA
14
52
1.82
4.43E−06
3′ss
Mel.



230657846-230659894
230657861-230659894
GGAGGCAGAGGA
GGAGGCAGCTTT





TCACAGGCTTTA
TCTCTCAACAGA





AAAT (387)
GGAT (388)





671
chr5:
chr5:
GCTCAGCCCCCT
TGACCCTGCAGC
5
20
1.81
2.74E−03
exon
Mel.



141694720-141699308
141694720-141704408
CCCCACAGGGCC
TCCTCAAAGGCC




incl.





CCTAGAAGCCTG
CCTAGAAGCCTG





TTTC (985)
TTTC (986)





672
chr19:
chr19:
GCCGACCCGCCT
GCCGACCCGCCT
3
13
1.81
4.16E−03
3′ss
Mel.



3542975-3544806
3544730-3544806
GCGACGCTCTTT
GCGACGCTGGGA





TCTTGCCTGGAG
CCGTGATGCCCG





AAGA (987)
GCCC (988)





673
chr3:
chr3:
TGCGGAGACCCC
TGCGGAGACCCC
1
6
1.81
2.67E−02
exon
Mel.



58417711-58419494
58419411-58419494
TTCGGGAGGTGA
TTCGGGAGGTCT




skip





CAGTTCGTGATG
CCGGGCTGCTGA





CTAT (989)
AGAG (990)





674
chr6:
chr6:
CTATCAGTAGGT
GCATTGATGTGG
1
6
1.81
2.71E−03
exon
Mel.



108370622-108370735
108370622-108372234
TTTTAGAGATGA
AAGATGCAATGA




incl.





ACATCACTCGAA
ACATCACTCGAA





AACT (991)
AACT (992)





675
chr6:
chr6:
GCATTGATGTGG
GCATTGATGTGG
1
6
1.81
1.84E−03
exon
Mel.



108370787-108372234
108370622-108372234
AAGATGCAGTTT
AAGATGCAATGA




incl.





TTTTCCTGGCAG
ACATCACTCGAA





AAGA (993)
AACT (992)





676
chr6:
chr6:
CAGTGGGCGGAT
CAGTGGGCGGAT
1
6
1.81
1.04E−02
3′ss
Mel.



166779550-166780282
166779594-166780282
GACATTTGGTAC
GACATTTGCCCT





AGCCTCGGAACT
CTGTTGCTATTC





GGCT (994)
TTTG (995)





677
chr7:
chr7:
GGTGTCCATGGC
GGTGTCCATGGC
1
6
1.81
4.73E−02
exon
Mel.



128033792-128034331
128033082-128034331
CTGCACTCCTAT
CTGCACTCTTAC




incl.





ACCTTTCTGCCG
GAAAAGCGGCTG





TGTA (996)
TACT (997)





678
chr6:
chr6:
ACTGGGAAGTTC
ACTGGGAAGTTC
10
37
1.79
1.30E−02
exon
Mel.



136597127-136599002
136597646-136599002
TTAAAAAGTCCC
TTAAAAAGGTTC




skip





CCTCTACACAAG
ACAGATGAAGAG





AATC (998)
TCTA (999)





679
chr16:
chr16:
GAGATTCTGAAG
GAGATTCTGAAG
20
69
1.74
1.28E−05
3′ss
Mel.



54954239-54957496
54954322-54957496
ATAAGGAGGATG
ATAAGGAGGTAA





CCACTGGAAATG
AACCTGTTTAGA





TTGA (322)
AATT (314)





680
chr4:
chr4:
GCTGAGCGGGGC
TCCAACAAGCAC
20
69
1.74
4.13E−05
exon
Mel.



17806394-17812069
17806394-17806729
GACCCGAGTCTT
CTCTGAAGTCTT




skip





CTCATTCACAGG
CTCATTCACAGG





TTAA (1000)
TTAA (832)





681
chr19:
chr19:
AGTGGCAGTGGC
AGTGGCAGTGGC
8
29
1.74
8.03E−04
3′ss
Mel.



6731065-6731209
6731122-6731209
TGTACCAGCCCA
TGTACCAGCTCT





CAGGAAACAACC
TGGTGGAGGGCT





CGTA (311)
CCAC (312)





682
chr16:
chr16:
TGTTCCACCTCC
TGTTCCACCTCC
6
22
1.72
2.96E−02
3′ss
Mel.



28842393-28843507
28842393-28843525
TCCTGCAGCTCC
TCCTGCAGTGGG





CCCTTTTCTTCC
CCGGATGTATCC





AGTG (1001)
CCCG (1002)





683
chr3:
chr3:
ACCCATGAGAAT
CTGGCCCCTGAG
8
28
1.69
8.95E−03
exon
Mel.



50615004-50617274
50616357-50617274
GCTCAGAGCTAT
ATCCGCAGCTAT




skip





GAAGACCCCGCG
GAAGACCCCGCG





GCCC (1003)
GCCC (1004)





684
chr11:
chr11:
CAAGCTCGAGTC
CAAGCTCGAGTC
4
15
1.68
8.31E−03
exon
Mel.



772521-774007
773629-774007
CATCGATGAACC
CATCGATGGTGC




skip





CATCTGCGCCGT
CCGGTACCATGC





CGGC (1005)
CCTC (1006)





685
chr2:
chr2:
CTTCACTGTCAC
CTTCACTGTCAC
9
30
1.63
2.25E−02
3′ss
Mel.



220424219-220427123
220426730-220427123
CGTCACAGAACC
CGTCACAGAGTC





CCCAGTGCGGAT
TTACCAAAGTCA





CATA (1007)
GGAC (1008)





686
chr3:
chr3:
GTCTTCCAATGG
GTCTTCCAATGG
10
33
1.63
1.04E−02
3′ss
Mel.



148759467-148759952
148759455-148759952
CCCCTCAGCCTT
CCCCTCAGGAAA





TTCTCTAGGAAA
TGATACACCTGA





TGAT (234)
AGAA (235)





687
chr5:
chr5:
AGAAACAGAAAC
AGAAACAGAAAC
5
17
1.58
1.55E−02
exon
Mel.



34945908-34949647
34945908-34950274
CAGCACAGGATG
CAGCACAGAATT




incl.





TACCTGGCAAAG
ATGATGACAATT





ATTC (1009)
TCAA (1010)





688
chr6:
chr6:
TTCTGCATCTGT
AAAGGAGTGCTT
2
8
1.58
1.45E−02
exon
Mel.



158589427-158613008
158591570-158613008
GGGCCGAGTGAT
ATAGAATGTGAT




skip





CCTGCCATGAAG
CCTGCCATGAAG





CAGT (1011)
CAGT (1012)





689
chr14:
chr14:
AGGATCGGCAAC
CTGGGATAAGAG
1
5
1.58
1.98E−02
exon
Mel.



23495584-23496953
23495584-23502576
ATGGCAAGGCCT
AGGCCCTGGCCT




incl.





CTACTACGTGGA
CTACTACGTGGA





CAGT (1013)
CAGT (1014)





690
chr6:
chr6:
GTTCAGGACACA
GGGAGGGAGAGA
1
5
1.58
1.23E−02
exon
Mel.



33669197-33678471
33669197-33679325
ATAAGCAGGTTG
ATACCCAGGTTG




incl.





CAGAGCCTGAGG
CAGAGCCTGAGG





CCTG (1015)
CCTG (1016)





691
chr10:
chr10:
TACCCGGATGAT
TACCCGGATGAT
0
2
1.58
2.58E−04
3′ss
Mel.



102286851-102289136
102286831-102289136
GGCATGGGAAGT
GGCATGGGGTAT





TCTTGCTGTCTT
GGCGACTACCCG





TCAG (1017)
AAGC (1018)





692
chr11:
chr11:
GACATATGAGTC
GACATATGAGTC
0
2
1.58
2.45E−02
3′ss
Mel.



66333872-66334716
66333875-66334716
AAAGGAAGCCCG
AAAGGAAGAAGC





GTGGCGCCTGTC
CCGGTGGCGCCT





CGTC (1019)
GTCC (1020)





693
chr11:
chr11:
CGGATCAACTTC
CGGATCAACTTC
0
2
1.58
2.65E−03
3′ss
Mel.



8705628-8706243
8705628-8706264
GACAAATAGTGG
GACAAATACCAC





TTGTTACCTCTT
CCAGGCTACTTT





CCTA (1021)
GGGA (1022)





694
chr12:
chr12:
TTATAGGCGTGA
TTATAGGCGTGA
0
2
1.58
1.03E−03
3′ss
Mel.



53421972-53427574
53421972-53427589
TGATAGAGTTTC
TGATAGAGGTCC





ATTTAACTTAGG
CCCCCAAAGACC





TCCC (1023)
CAAA (1024)





695
chr15:
chr15:
TGGAAATATTTC
GCCTCACTGAGC
0
2
1.58
7.87E−03
exon
Mel.



25212387-25213078
25207356-25213078
TAGACTTGGTGT
AACCAAGAGTGT




incl.





CAGTTGTACCCG
CAGTTGTACCCG





AGGC (1025)
AGGC (145)





696
chr1:
chr1:
TCGGCCCAGAAG
CTTAGGAAAGAC
0
2
1.58
4.66E−02
5′ss
Mel.



1480382-1497338
1480382-1500152
AACCCCGCCTAT
AAAGAACTCTAT





ACACAGAATGGG
ACACAGAATGGG





ATTT (1026)
ATTT (957)





697
chr5:
chr5:
TCTATATCCCCT
TCTATATCCCCT
0
2
1.58
1.26E−04
3′ss
Mel.



177576859-177577888
177576839-177577888
CTAAGACGCACT
CTAAGACGGACC





TCTTTCCCCTCT
TGGGTGCAGCCG





GTAG (299)
CAGG (300)





698
chr6:
chr6:
GCTGAAGGGAAA
GCTGAAGGGAAA
0
2
1.58
4.68E−02
3′ss
Mel.



42905945-42911535
42905945-42906305
AGACACCAAAAC
AGACACCAGTTG





ACAAACAGCAGA
CCTGGCAGAGCA





ATGG (1027)
GTGG (1028)





699
chr17:
chr17:
CATCATCAAGTT
CATCATCAAGTT
5
16
1.50
1.74E−04
intron
Mel.



2282497-2282499
2282497-2282725
TTTCAATGACGA
TTTCAATGAACG




reten-





GCTGGTCCAGCC
TGCTGAGCATCA




tion





ATCC (1029)
CGAT (1030)





700
chr8:
chr8:
GAGGGCCTGCTC
ACATGCTTCAAA
23
66
1.48
1.49E−03
exon
Mel.



74601048-74621266
74601048-74650518
ATTCAAAGATGT
TAAATCAGATGT




incl.





TCTCAGTGCAGC
TCTCAGTGCAGC





TGAG (1031)
TGAG (1032)





701
chr10:
chr10:
CTGAGGCTAATG
CTGAGGCTAATG
14
40
1.45
2.13E−02
3′ss
Mel.



35495979-35500583
35495979-35500181
AAAAACAGGGAA
AAAAACAGGGAA





GCTGCCAAAGAA
GCTGCCCGGGAG





TGTC (1033)
TGTC (1034)





702
chr3:
chr3:
CGGCTGGGACTC
CGGCTGGGACTC
12
34
1.43
1.81E−02
3′ss
Mel.



119180951-119182182
119180995-119182182
TTCCATGCGTGG
TTCCATGCAGTT





CACTGGAAGCAG
GAAACTGGTTGA





ACTG (1035)
CAAC (1036)





703
chr4:
chr4:
AGTGAATGTAGT
AGTGAATGTAGT
17
47
1.42
2.45E−02
exon
Mel.



169919436-169923221
169911479-169923221
TGCACCAGTGAC
TGCACCAGGATT




incl.





AATACTTGTATG
TGTACACACAGA





GAGT (1037)
TATG (1038)





704
chr17:
chr17:
ATTCACACAGAG
TGAGGATCAATC
2
7
1.42
1.30E−02
exon
Mel.



55074416-55078215
55075859-55078215
CCACCTAGGCCA
CTGGGGAGGCCA




skip





GGCTACCAACGT
GGCTACCAACGT





CTTT (1039)
CTTT (1040)





705
chrX:
chrX:
AGAAACCTTGAA
AGAAACCTTGAA
7
20
1.39
3.40E−02
exon
Mel.



2310515-2326785
2209644-2326785
CGACAAAGAGAC
CGACAAAGTGGA




incl.





GTGAGTCTTGCT
ATTTTTATACTG





GTGT (496)
TGAC (495)





706
chrY:
chrY:
AGAAACCTTGAA
AGAAACCTTGAA
7
20
1.39
3.40E−02
exon
Mel.



2260515-2276785
2159644-2276785
CGACAAAGAGAC
CGACAAAGTGGA




incl.





GTGAGTCTTGCT
ATTTTTATACTG





GTGT (496)
TGAC (495)





707
chr5:
chr5:
TGGAAAAGTATA
TGGAAAAGTATA
4
12
1.38
2.71E−02
exon
Mel.



54456224-54459882
54456224-54456821
AAGGCAAAATTC
AAGGCAAAGTTT




skip





TTCAAAGAAGGA
CACTAGTTGTAA





ACCA (1041)
ACGT (1042)





708
chr15:
chr15:
ATACTAAGAACA
ATACTAAGAACA
19
50
1.35
2.54E−02
exon
Mel.



76146828-76161291
76146828-76152218
ACAATTTGAATG
ACAATTTGCTTC




skip





GGACAACAGAAG
GTCAGCAATTGA





AAGT (1043)
AGTG (1044)





709
chr8:
chr8:
TGGCCTTGACCT
TGGCCTTGACCT
7
19
1.32
3.77E−02
3′ss
Mel.



38270113-38271435
38271322-38271435
CCAACCAGGTCC
CCAACCAGGAGT





TGCACCCAGACC
ACCTGGACCTGT





TCAC (1045)
CCAT (1046)





710
chr1:
chr1:
GAAGGCAGCTGA
GAAGGCAGCTGA
3
9
1.32
1.42E−02
3′ss
Mel.



11131045-11132143
11131030-11132143
GCAAACAGTTCT
GCAAACAGCTGC





CTCCCTTGCAGC
CCGGGAACAGGC





TGCC (393)
AAAG (394)





711
chr11:
chr11:
TCCTTGAACACT
TCCTTGAACACT
1
4
1.32
2.52E−02
exon
Mel.



62556898-62557357
62556898-62557072
ACAATTAGACCT
ACAATTAGCTGT




skip





CTTCTTGGGTGA
TCTGAAGCCCAG





ATTT (1047)
AAAA (1048)





712
chr14:
chr14:
ACACCATTGAGG
ACACCATTGAGG
1
4
1.32
1.92E−02
exon
Mel.



69349309-69350884
69349772-69350884
AGATCCAGGTGC
AGATCCAGGGAC




skip





GGCAGCTGGTGC
TGACCACAGCCC





CTCG (1049)
ATGA (1050)





713
chr1:
chr1:
CCCATGTATAAG
CCCATGTATAAG
1
4
1.32
2.77E−02
3′ss
Mel.



155227125-155227288
155227177-155227288
GCTTTCCGGATG
GCTTTCCGGAGT





TGCTCTTTGTCC
GACAGTTCATTC





TCCA (1051)
AATT (1052)





714
chr20:
chr20:
CTCCCAGTGCTG
GAGCTGCCACGG
1
4
1.32
2.02E−02
exon
Mel.



25281520-25281967
25281520-25282854
TATATCCCGGAA
ATACTGAGGGAA




incl.





.TTCCTGGGGAAG
TTCCTGGGGAAG





TCGG (1053)
TCGG (1054)





715
chr7:
chr7:
GGATGCGCGTCT
AGCCGCAGAGCA
1
4
1.32
4.91E−02
exon
Mel.



142962185-142964709
142962389-142964709
GGTCAAGGGCTG
TCCTGGCGGCTG




skip





CAGAGAAGGCTG
CAGAGAAGGCTG





GTAT (1055)
GTAT (1056)





716
chr8:
chr8:
ACATGCTTCAAA
ACATGCTTCAAA
24
61
1.31
1.74E−02
exon
Mel.



74621397-74650518
74601048-74650518
TAAATCAGCTTC
TAAATCAGATGT




incl.





TCTCCAAGATAA
TCTCAGTGCAGC





AATG (1057)
TGAG (1032)





717
chr15:
chr15:
AACAAAGAAATA
CTGAGTCTTTAT
16
41
1.30
1.66E−03
exon
Mel.



49309825-49319561
49309825-49311614
ATTCACAGGATG
ATTTTGAGGATG




skip





AAGATGGGTTTC
AAGATGGGTTTC





AAGA (1058)
AAGA (1059)





718
chrX:
chrX:
TAGCCACCACTG
GGGAAAAGTCTT
11
28
1.27
1.07E−02
exon
Mel.



148582568-148583604
148582568-148584841
TGTGCCAGGGAT
TCACCCTGGGAT




incl.





ATCTTCTAACCA
ATCTTCTAACCA





TACC (1060)
TACC (1061)





719
chr12:
chr12:
CCTACCAGCCAC
CCTACCAGCCAC
4
11
1.26
2.42E−02
3′ss
Mel.



49918679-49919860
49918679-49919726
TTCGGGAGGTAT
TTCGGGAGGTAT





CAGAGTGCTCCA
TGCCAGGGAACA





TCTC (1062)
GACG (1063)





720
chr1:
chr1:
GTCCCGGCTTCC
GTCCCGGCTTCC
4
11
1.26
2.67E−02
exon
Mel.



46654652-46655129
46655029-46655129
CCCTACTCGCCT
CCCTACTCAGTG




skip





GGCTCAGAATCT
AAGAAGCCACCC





AACC (1064)
TCAG (1065)





721
chr3:
chr3:
CTTAAGCATATA
CTTAAGCATATA
28
68
1.25
2.24E−02
exon
Mel.



105397415-105400567
105400454-105400567
TTTAAAGGGTGA
TTTAAAGGGAGA




skip





AGATGCTTTTGA
TGTTTTTGATTC





TGCC (1066)
AGCC (1067)





722
chr3:
chr3:
CAGGAACAAGTA
CAGGAACAAGTA
2
6
1.22
4.97E−02
exon
Mel.



10023431-10028190
10019130-10028190
TCTGACAGAAAA
TCTGACAGTCAA




incl.





TATCTTTCAGGC
GTCCTAATTCGA





CTGG (1068)
AGCA (1069)





723
chr4:
chr4:
GAAGTTCTGAGG
GAAGTTCTGAGG
2
6
1.22
1.07E−02
3′ss
Mel.



88898249-88901544
88898249-88901197
AAAAGCAGAATG
AAAAGCAGCTTT





CTGTGTCCTCTG
ACAACAAATACC





AAGA (1070)
CAGA (1071)





724
chr7:
chr7:
ATCTCCCTCTTG
ATCTCCCTCTTG
2
6
1.22
1.94E−03
3′ss
Mel.



23313233-23313672
23313233-23313683
GTGTACAAATTG
GTGTACAAAAAA





TTTTCAGAAAAC
CACAAGGAATAC





ACAA (1072)
AACC (1073)





725
chr1:
chr1:
TGCGAGTACTGC
TGCGAGTACTGC
6
15
1.19
3.00E−03
exon
Mel.



214454770-214488104
214454770-214478529
TTCACCAGAAAG
TTCACCAGGAAA




skip





AAGATTGGCCCA
GAAGGATTGTCC





TGCA (1074)
AAAT (1075)





726
chr15:
chr15:
TCCAGAAAGTGA
TCCAGAAAGTGA
15
35
1.17
2.02E−04
exon
Mel.



101826006-101827112
101826498-101827112
AACTAAAATTTT
AACTAAAAGAGC




skip





AATCCAGGTGCT
GTCAGGAAGCAG





GGTT (1076)
AGAA (1077)





727
chr15:
chr15:
ACTCAGATGCCG
ACTCAGATGCCG
39
88
1.15
2.54E−04
3′ss
Mel.



74326871-74327483
74326871-74327512
AAAACTCGCCCT
AAAACTCGTGCA





CAGTCTGAGGTT
TGGAGCCCATGG





CTGT (748)
AGAC (749)





728
chrX:
chrX:
AGATTCTACAGA
AGATTCTACAGA
17
39
1.15
2.23E−02
exon
Mel.



15706981-15720904
15706981-15711085
TAAATCAGATTT
TAAATCAGCTGC




skip





CGGAAACTTCTG
ACTTAGTGCATT





GCAG (1078)
GGAA (1079)





729
chr3:
chr3:
TGGCTGGCTTCA
TGGCTGGCTTCA
40
90
1.15
1.67E−02
exon
Mel.



183703166-183705557
183700795-183705557
GTGGACCAAATT
GTGGACCAGCCT




incl.





TTCAGGATGGCT
TCATGGTGAAAC





GTAT (1080)
ACCT (1081)





730
chr16:
chr16:
CCCTGCTCATCA
CCCTGCTCATCA
19
40
1.04
9.38E−04
exon
Mel.



684797-685280
684956-685280
CCTACGGGGAAC
CCTACGGGCCCT




skip





CCAGAATGGGGG
ATGCCATCAATG





CTTC (1082)
GGAA (194)





731
chrX:
chrX:
CAAACACCTCTT
CAAACACCTCTT
11
23
1.00
2.44E−04
exon
Mel.



123224614-123224703
123224614-123227867
GATTATAACACG
GATTATAATCGG




incl.





CAGGTAACATGG
CGTGGCACAAGC





ATGT (468)
CTAA (457)





732
chr20:
chr20:
GGCAGCCACCAC
TGATAATTGGGC
10
21
1.00
2.87E−02
exon
Mel.



48700791-48729643
48700791-48713208
GGGCTCGGACAA
CTCCAAGAACAA




skip





TTTATGAAAACC
TTTATGAAAACC





GAAT (1083)
GAAT (1084)





733
chr19:
chr19:
ACCGCCCTGCAC
ACCGCCCTGCAC
7
15
1.00
2.95E−02
3′ss
Mel.



617870-618487
617849-618487
TGCTACAGGAGT
TGCTACAGGAAG





CCTCCGCTCTGC
GGCCTGACCTTC





CACA (1085)
GTCT (1086)





734
chr1:
chr1:
TCACAATTATAG
GTGCTATTAAAG
7
15
1.00
1.48E−02
exon
Mel.



220242774-220247308
220242774-220246191
GGGAAGAGCTCG
AAGAAGATCTCG




skip





TGGTCTGGGTTG
TGGTCTGGGTTG





ATCC (1087)
ATCC (1088)





735
chr1:
chr1:
CTCGTCTATGAT
CTCGTCTATGAT
6
13
1.00
3.26E−02
3′ss
Mel.



229431657-229433266
229431657-229433228
ATCACCAGATGC
ATCACCAGCCGA





CCGAATGCTAGC
GAAACCTACAAT





GAGC (1089)
GCGC (1090)





736
chr11:
chr11:
CAATGCCACAGG
CAATGCCACAGG
4
9
1.00
1.30E−02
3′ss
Mel.



57193182-57193461
57193143-57193461
GCAGGCTGGAAG
GCAGGCTGACTG





GCTGGGATGCAT
CAAAGCCCAGGA





GGGA (1091)
TGAG (1092)





737
chr11:
chr11:
TCAGAAGAGAAA
TCAGAAGAGAAA
3
7
1.00
3.02E−02
3′ss
Mel.



66105278-66105713
66105360-66105713
ATCGGATGACAG
ATCGGATGGACC





GCGGACCCACAG
TTGACCCTGCTG





GCCC (1093)
TTCA (1094)





738
chr7:
chr7:
TGACTGCCGCTT
CTAAAGCCTTCT
3
7
1.00
2.44E−02
exon
Mel.



44251203-44251845
44250723-44251845
TCTCTCAGGCCC
ATAAAACTGCCC




incl.





GGAAACAAAACT
GGAAACAAAACT





CATG (1095)
CATG (1096)





739
chr12:
chr12:
ATGCAGATACAC
ATGCAGATACAC
2
5
1.00
1.43E−02
exon
Mel.



57925889-57926354
57926098-57926354
AAAGCAAGCCAT
AAAGCAAGGTGC




skip





GCAGTTTGGTCA
ACCAGCTATATG





GCTC (1097)
AAAC (1098)





740
chr4:
chr4:
TACTGATCATAT
AAGAGTGCCAAA
2
5
1.00
2.55E−03
exon
Mel.



48853992-48862741
48859382-48862741
TGTCCAAGTCAA
AAAAGAAGTCAA




skip





AGTAAACAAGTA
AGTAAACAAGTA





TGGA (1099)
TGGA (1100)





741
chr2:
chr2:
TGTCATCCATTG
TGTCATCCATTG
1
3
1.00
2.77E−02
3′ss
Mel.



27604588-27604992
27604672-27604992
TGGAAGAGCCCC
TGGAAGAGCTGC





GAAACACAGCAG
TGGATCAGTGCC





AGCT (1101)
TGGC (1102)





742
chr6:
chr6:
TACCGGAAACCT
GCTGCCAAAGCC
1
3
1.00
4.97E−02
5′ss
Mel.



133136363-133137599
133136227-133137599
AGGAAAAGGCGC
TTAGACAAGCGC





CAAGCCCATCTT
CAAGCCCATCTT





TGTG (1103)
TGTG (1104)





743
chr12:
chr12:
GGGTGCAAAAGA
GGGTGCAAAAGA
0
1
1.00
8.93E−03
3′ss
Mel.



57032980-57033763
57033091-57033763
TCCTGCAGCCAT
TCCTGCAGGACT





TCCAGGTTGCTG
ACAAATCCCTCC





AGGT (283)
AGGA (284)





744
chr14:
chr14:
AGGATATCGGTT
AGGATATCGGTT
0
1
1.00
1.46E−02
3′ss
Mel.



50044571-50052667
50050393-50052667
TCATTAAGAAAG
TCATTAAGTTGG





ACCTGAGCTGTC
ACTAAATGCTCT





TTCC (1105)
TCCT (1106)





745
chr16:
chr16:
GCGGCGGGCAGT
GCGGCGGGCAGT
0
1
1.00
1.39E−02
3′ss
Mel.



85833358-85834789
85833358-85834810
GGCGGCAGGTGT
GGCGGCAGAATG





ACATTTTTATCT
TTGGCTACCAGG





TTCA (1107)
GTAT (1108)





746
chr19:
chr19:
TATCCAGCACTG
CCTGATTCTCCC
0
1
1.00
3.56E−02
exon
Mel.



35647877-35648323
35646514-35648323
ACCACATGGACA
CACCAGAGGACA




incl.





GACGTTGAAAGA
GACGTTGAAAGA





TACC (1109)
TACC (1110)





747
chr21:
chr21:
TTCATCATGGTG
TTCATCATGGTG
0
1
1.00
1.84E−02
3′ss
Mel.



27254101-27264033
27254082-27264033
TGGTGGAGCTCT
TGGTGGAGGTTG





CCTCTTGTTTTT
ACGCCGCTGTCA





CAGG (1111)
CCCC (1112)





748
chr21:
chr21:
TGAAATCAGAAA
TGAAATCAGAAA
0
1
1.00
3.04E−02
3′ss
Mel.



46271557-46275124
46271542-46275124
AAAATATGTTTA
AAAATATGGCCT





TTTTGTTTCAGG
GTTTAAAGAAGA





CCTG (1113)
AAAC (1114)





749
chr3:
chr3:
CAACGAGAACAA
CAACGAGAACAA
0
1
1.00
4.76E−04
3′ss
Mel.



101401353-101401614
101401336-101401614
GCTATCAGTTAC
GCTATCAGGGCT





TTTTACCCCACA
GCTAAGGAAGCA





GGGC (297)
AAAA (298)





750
chr4:
chr4:
CCATGGTCAAAA
CCATGGTCAAAA
0
1
1.00
4.92E−05
3′ss
Mel.



152022314-152024139
152022314-152024022
AATGGCAGCACC
AATGGCAGACAA





AACAGGTCCGCC
TGATTGAAGCTC





AAAT (344)
ACGT (345)





751
chr9:
chr9:
GCAAGGATATAT
GCAAGGATATAT
0
1
1.00
4.68E−04
3′ss
Mel.



86593213-86593287
86593194-86593287
AATAACTGCTGC
AATAACTGATTG





TTTATTTTTCCA
GTGTGCCCGTTT





CAGA (1115)
AATA (1116)





752
chr4:
chr4:
GAACTGCAAAGG
AGTGAATGTAGT
27
54
0.97
4.49E−02
exon
Mel.



169911479-169919352
169911479-169923221
CTTCAGAGGATT
TGCACCAGGATT




incl.





TGTACACACAGA
TGTACACACAGA





TATG (1117)
TATG (1038)





753
chrX:
chrX:
TTGGAGATCAGG
GATCTGGATTCT
21
42
0.97
2.52E−02
5′ss
Mel.



102940188-102942916
102940188-102941558
ACGCAAAGGTCA
CGTTTCAGGTCA





CCATCAGAAAAG
CCATCAGAAAAG





CTAA (1118)
CTAA (1119)





754
chr5:
chr5:
TGGAAGAGGCTA
TGGAAGAGGCTA
13
26
0.95
2.18E−02
exon
Mel.



137503767-137504910
137504377-137504910
CCTCTGGGGTCA
CCTCTGGGGTAA




skip





ATGAGAGTGAAA
CCCCCGGGACTT





TGGC (1120)
TGCC (1121)





755
chr13:
chr13:
TCTGGAGCCATA
TCTGGAGCCATA
11
22
0.94
4.45E−02
exon
Mel.



114291015-114294434
114291015-114292132
CGTGACAGTGAC
CGTGACAGAAAT




skip





CTGACCAACGGT
GGCTCAGGGAAC





GCAG (1122)
TGTT (1123)





756
chr16:
chr16:
CATCAAGCAGCT
CATCAAGCAGCT
11
22
0.94
4.68E−04
3′ss
Mel.



57473207-57474683
57473246-57474683
GTTGCAATGTTT
GTTGCAATCTGC





AGTCCCAGGAAG
CCACAAAGAATC





CACC (822)
CAGC (823)





757
chr22:
chr22:
CTGCAGTATCTG
CTGCAGTATCTG
28
52
0.87
1.79E−02
3′ss
Mel.



31724845-31731677
31724910-31731677
TAACCGAGGTCT
TAACCGAGGTTT





CCAGGCACCAGG
CTCCTCTGCCTC





AGCC (1124)
CTAC (1125)





758
chrX:
chrX:
ACTAATCTTCAG
CAAACACCTCTT
14
26
0.85
1.55E−02
exon
Mel.



123224814-123227867
123224614-123227867
CATGCCATTCGG
GATTATAATCGG




incl.





CGTGGCACAAGC
CGTGGCACAAGC





CTAA (456)
CTAA (457)





759
chr7:
chr7:
TGATTTCAAGTT
TGATGAGACTCC
56
100
0.83
5.42E−03
exon
Mel.



5028808-5036240
5035213-5036240
TGAACAAGGGGT
AGACAGAGGGGT




skip





TGGCATCTGCAC
TGGCATCTGCAC





ATCC (1126)
ATCC (1127)





760
chr8:
chr8:
AGCGAGCTCCTC
CCGGGGATTGCC
29
52
0.82
4.95E−02
5′ss
Mel.



146076780-146078756
146076780-146078377
AGCCTCAGGCAT
GGCGCCAGGCAT





CTGCATCTGGGA
CTGCATCTGGGA





CCGA (1128)
CCGA (1129)





761
chr5:
chr5:
AGTTTCTACTAG
AGTTTCTACTAG
7
13
0.81
3.69E−03
exon
Mel.



139909381-139916922
139909381-139914946
TCCAGTTGGTGA
TCCAGTTGGGTT




skip





CTCTCCTATTCC
ACCATCCATTGA





ATCT (1130)
CCCA (1131)





762
chr1:
chr1:
CATAGTGGAAGT
CATAGTGGAAGT
42
69
0.70
1.02E−05
3′ss
Mel.



67890660-67890765
67890642-67890765
GATAGATCTTCT
GATAGATCTGGC





TTTTCACATTAC
CTGAAGCACGAG





AGTG (444)
GACA (445)





763
chr22:
chr22:
GGAAAGGACAGC
TGAGGTGCCCTA
40
65
0.69
3.49E−02
exon
Mel.



42557364-42564614
42557364-42565852
AAGCACAGGTGA
AGCACAAGGTGA




incl.





GACTGTGGAGAT
GACTGTGGAGAT





GAGA (1132)
GAGA (1133)





764
chr6:
chr6:
AGTTGCATGTTG
AGTTGCATGTTG
4
7
0.68
3.75E−03
exon
Mel.



30587766-30592659
30587766-30590608
ACTTTAGGGAGT
ACTTTAGGAACG




skip





CTGTGTGAAGCA
TGAAGCTCTTGG





GCAC (1134)
AGCA (1135)





765
chr19:
chr19:
CCGCCCCCGTTC
CCGCCCCCGTTC
41
65
0.65
1.89E−02
3′ss
Mel.



2112966-2113334
2112930-2113334
CATCCACGGGGG
CATCCACGGACG





AGCTCAGTGTGA
AGTGTGAGGACG





ACAC (1136)
CCAA (1137)





766
chr16:
chr16:
TGGAGCCGAACA
TGGAGCCGAACA
8
13
0.64
4.20E−03
3′ss
Mel.



89960266-89961490
89960266-89961445
ACATCGTGCTCA
ACATCGTGGTTC





GCGATGCCTGCC
TGCTCCAGACGA





GCTT (1138)
GCCC (1139)





767
chr10:
chr10:
TGACGTTCTCTG
TGACGTTCTCTG
47
73
0.62
1.42E−03
3′ss
Mel.



75554088-75554298
75554088-75554313
TGCTCCAGTGGT
TGCTCCAGGTTC





TTCTCCCACAGG
CCGGCCCCCAAG





TTCC (466)
TCGC (467)





768
chr12:
chr12:
GCCTGGAAAGCT
GCCTGGAAAGCT
28
42
0.57
1.37E−03
3′ss
Mel.



6675490-6675694
6675502-6675694
ACCAAAAGGAGC
ACCAAAAGGGAT





TGTCCAGACAGC
CTCTGCAGGAGC





TGGT (1140)
TGTC (1141)





769
chr11:
chr11:
TGTTATTGTAGA
TGTTATTGTAGA
37
55
0.56
4.34E−05
3′ss
Mel.



85693031-85694908
85693046-85694908
TTCTGGGGGTGG
TTCTGGGGGCTT





ACTTCTCAAACC
TGATGAACTAGG





AACA (1142)
TGGA (1143)





770
chr2:
chr2:
GGGGACCAAGAA
GGGGACCAAGAA
59
86
0.54
2.26E−02
exon
Mel.



55530288-55535944
55529208-55535944
AAGCAGCATGGT
AAGCAGCACCAT




incl.





TGCACTGAAAAG
GAATGACCTGGT





ACTG (1144)
GCAG (1145)





771
chr12:
chr12:
CAAAAAAGACCA
CAAAAAAGACCA
13
19
0.51
2.94E−02
3′ss
Mel.



7043741-7044712
7043741-7044709
AAACTGAGGAAC
AAACTGAGCAGG





TCCCTCGGCCAC
AACTCCCTCGGC





AGTC (1146)
CACA (1147)





772
chr1:
chr1:
CCAAAGCAGAGA
CCAAAGCAGAGA
9
13
0.49
3.58E−02
3′ss
Mel.



40209596-40211085
40209596-40211046
CCCAGGAGGTGT
CCCAGGAGGGAG





ACATGGACATCA
AGCCCATTGCTA





AGAT (1148)
AAAA (1149)





773
chr4:
chr4:
ACTGGGCTTCCA
ACTGGGCTTCCA
63
86
0.44
9.76E−04
exon
Mel.



54266006-54280781
54266006-54292038
CCGAGCAGAAAC
CCGAGCAGGAGA




incl.





AGCACTTCTTCT
TTACCTGGGGCA





CAGT (848)
ATTG (849)





774
chr20:
chr20:
TGCCTAAGGCGG
TGCCTAAGGCGG
61
83
0.44
3.34E−02
3′ss
Mel.



30310151-30310420
30310133-30310420
ATTTGAATCTCT
ATTTGAATAATC





TTCTCTCCCTTC
TTATCTTGGCTT





AGAA (479)
TGGA (480)





775
chr4:
chr4:
GCCGAATCACCT
ACTGGGCTTCCA
63
84
0.41
3.70E−03
exon
Mel.



54280889-54292038
54266006-54292038
GATCTAAGGAGA
CCGAGCAGGAGA




incl.





TTACCTGGGGCA
TTACCTGGGGCA





ATTG (1150)
ATTG (849)





776
chr1:
chr1:
ACGCCGCAAGTC
AGCACCCATGGG
66
87
0.39
2.24E−02
exon
Mel.



47024472-47025905
47024472-47027149
CTCCAGAGGAAC
TGCAGGGGGAAC




incl.





AGCAGCACAATG
AGCAGCACAATG





GACC (1151)
GACC (1152)





777
chr1:
chr1:
AACCAGTAACAA
AACCAGTAACAA
59
76
0.36
1.42E−02
3′ss
Mel.



150249040-150252050
150249040-150252053
CGGAACCTCAGA
CGGAACCTAGTC





GTCCAGATCTGA
CAGATCTGAACG





ACGA (1153)
ATGC (1154)





778
chr20:
chr20:
GAGACCGCGTGC
GAGACCGCGTGC
70
90
0.36
3.80E−03
3′ss
Mel.



62577996-62587612
62577993-62587612
GAGGACCGCAGC
GAGGACCGCAAT





AATGCAGAGTCC
GCAGAGTCCCTG





CTGG (1155)
GACA (1156)





779
chr1:
chr1:
GTCTCTGGCAAG
GTCTCTGGCAAG
78
100
0.35
3.86E−02
3′ss
Mel.



211836994-211840447
211836970-211840447
TAATCCAGAACT
TAATCCAGTAAT





TCTTAATCTTCC
TAAGAAGAAAGT





ATCC (1157)
TCAT (1158)





780
chr3:
chr3:
AAGCATGTAGAA
AAGCATGTAGAA
44
56
0.34
4.73E−02
3′ss
Mel.



133305566-133306002
133305566-133306739
AGCCGGAACAGG
AGCCGGAAGGAT





TACTTAAAATGA
AAAGAAATGGAG





ATGC (1159)
AAGA (1160)





781
chr1:
chr1:
AGCACCCATGGG
AGCACCCATGGG
69
87
0.33
4.36E−02
exon
Mel.



47025949-47027149
47024472-47027149
TGCAGGGGCAAG
TGCAGGGGGAAC




incl.





CTCCAGAAAAGG
AGCAGCACAATG





GACT (1161)
GACC (1152)





782
chr1:
chr1:
TCCACAAGAGCG
AGGCGGTGAGTG
46
58
0.33
4.32E−02
5′ss
Mel.



17330906-17331201
17330906-17331186
AGGAGGCGAAGC
TCGGACAGAAGC





GGGTGCTGCGGT
GGGTGCTGCGGT





ATTA (1162)
ATTA (1163)





783
chr1:
chr1:
TCCGCCCCACAG
GGCGGAGACATG
74
91
0.29
8.93E−03
5′ss
Mel.



155917806-155920089
155917806-155920059
TCCACGAGACTT
GACCAGAGACTT





TACCAGAATGCA
TACCAGAATGCA





GGAC (1164)
GGAC (1165)





784
chr17:
chr17:
TTGATCTTCGGC
TTGATCTTCGGC
72
84
0.22
4.78E−02
3′ss
Mel.



38080478-38083736
38080473-38083736
CCCACACGAACA
CCCACACGCAGA





GCAGAGAGGGGC
GAGGGGCAGCAG





AGCA (1166)
GATG (1167)





785
chr2:
chr2:
GAAAAACTTTCC
GAAAAACTTTCC
81
94
0.21
4.90E−02
3′ss
Mel.



242590750-242592926
242590750-242592721
AGCCATTGGGGG
AGCCATTGGAGG





GACAGGCCCCAC
TTGTCGGGACAT





CTCG (1168)
TTCA (1169)





786
chr9:
chr9:
GCGCTCGCCCGG
CCGCAGGATACC
76
86
0.18
2.12E−02
5′ss
Mel.



37422830-37424841
37422802-37424841
GCGGCAGACTGT
CGCCGAGGCTGT





GAGGTGGAGCAG
GAGGTGGAGCAG





TGGG (1170)
TGGG (1171)





787
chr20:
chr20:
CGGGACGACTTC
GCAGCATCTGCC
78
86
0.14
3.03E−02
exon
Mel.



32661672-32663679
32661441-32663679
TACGACAGGCTC
ATATACAGGCTC




incl.





TTCGACTACCGG
TTCGACTACCGG





GGCC (1172)
GGCC (1173)





788
chr3:
chr3:
ACTGAAGCAGCA
ACTGAAGCAGCA
92
98
0.09
3.80E−03
3′ss
Mel.



184084588-184085964
184084588-184085900
ACACGCCTCTCT
ACACGCCTGCTG





GCGTACGTGTCC
AGATTGAGAGCT





TATG (1174)
GCTG (1175)





789
chr19:
chr19:
CTGCCGGCGGAG
CTGCCGGCGGAG
93
99
0.09
7.19E−03
3′ss
Mel.



58817582-58823531
58817582-58823562
AATATAAGGAGA
AATATAAGGTGT





TGGACAAACCGT
GTGTGACCATGG





GTGG (1176)
AACG (1177)





790
chr5:
chr5:
CAACCTCTAAGA
CAACCTCTAAGA
97
99
0.03
2.75E−02
3′ss
Mel.



179225591-179225927
179225576-179225927
CTGGAGCGGTTC
CTGGAGCGTGGG





TTCTTCCGCAGT
AACATCGAGCAC





GGGA (1178)
CCGG (1179)









Certain splice variants are associated with more than one disease, and thus appear in Table 1 more than one time. In certain instances, splice variants associated with more than one cancer type may have different expression levels in each disease, so there may be more than one set of expression data for a given splice variant. Variants differentially expressed across all tested cancer types can be used to evaluate cells having SF3B1 neomorphic mutations in additional cancer types. Such variants are shown in the following rows of Table 1 (triplicates represent the same splice junction, measured in different cancer types): [13, 272, 525], [27, 286, 527], [33, 536, 330], [107, 445, 657], [28, 350, 573], [229, 762, 467], [240, 508, 767], [7, 356, 524], [76, 374, 596], [35, 547, 280], [84, 364, 571], [85, 564, 297], [24, 597, 296], [21, 372, 545], [36, 576, 407], [105, 423, 639], [62, 580, 447], [31, 279, 528], [235, 758, 439], [306, 89, 666], [34, 295, 533], [390, 72, 640], [48, 343, 554], [360, 65, 540], [178, 329, 750], [71, 265, 556], [15, 283, 530], [18, 267, 583], [129, 418, 622], [333, 25, 541], [247, 500, 774], [259, 5, 542], [152, 438, 615], [292, 1, 517], [81, 543, 443], [347, 70, 592], [91, 431, 617], [30, 298, 582], [17, 334, 602], [16, 276, 559], [51, 426, 548], [118, 401, 566], [83, 435, 574], and [269, 45, 546]. In certain embodiments, variants that are nonspecific to a particular cancer type can be chosen from the following rows of Table 1: [13, 272, 525], [27, 286, 527], [33, 536, 330], [107, 445, 657], [28, 350, 573], [240, 508, 767], [7, 356, 524], [84, 364, 571], [24, 597, 296], [21, 372, 545], [105, 423, 639], [62, 580, 447], [31, 279, 528], [235, 758, 439], [306, 89, 666], [34, 295, 533], [390, 72, 640], [360, 65, 540], [178, 329, 750], [71, 265, 556], [15, 283, 530], [18, 267, 583], [247, 500, 774], [152, 438, 615], [292, 1, 517], [81, 543, 443], [91, 431, 617], [30, 298, 582], [16, 276, 559], or [51, 426, 548].


Certain embodiments of the invention provide splice variants as markers for cancer. In certain circumstances, cancer cells with a neomorphic SF3B1 protein demonstrate differential expression of certain splice variants compared to cells without a neomorphic SF3B1 protein. The differential expression of one or more splice variants therefore may be used to determine whether a patient has cancer with a neomorphic SF3B1 mutation. In certain embodiments, the patient is also determined to have a cancer cell having a mutant SF3B1 protein. In these methods, one or more of the splice variants listed in Table 1 can be measured to determine whether a patient has cancer with a neomorphic SF3B1 mutation. In certain embodiments, one or more aberrant splice variants from Table 1 are measured. In other embodiments, one or more canonical splice variants are measured. Sometimes, both aberrant and canonical variants are measured.


In some embodiments, one or more aberrant splice variants selected from rows 260, 262, 263, 265, 266, 267, 272, 273, 275, 276, 277, 279, 281, 282, 286, 287, 288, 290, 294, 295, 296, 298, 299, 301, 302, 304, 305, 306, 308, 310, 312, 313, 315, 316, 318, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 335, 337, 339, 342, 346, 348, 349, 350, 352, 353, 354, 355, 356, 357, 358, 362, 363, 365, 366, 368, 369, 370, 372, 375, 377, 378, 379, 380, 381, 382, 383, 384, 387, 388, 389, 390, 391, 392, 393, 394, 397, 398, 400, 402, 403, 404, 405, 406, 413, 415, 416, 417, 419, 420, 421, 424, 425, 428, 429, 430, 431, 432, 433, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 454, 455, 456, 458, 459, 460, 461, 462, 464, 465, 468, 469, 471, 472, 473, 474, 475, 476, 477, 478, 480, 481, 483, 484, 485, 486, 487, 488, 490, 491, 494, 496, 497, 498, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 513, 514, 515, or 516 of Table 1 can be measured in a patient suspected of having CLL. In additional embodiments, a patient suspected of having CLL can be identified by measuring the amounts of one or more of the following aberrant splice variants listed in Table 1: row 259, 269, 270, 271, 274, 278, 280, 282, 292, 296, 297, 302, 306, 330, 331, 333, 343, 347, 355, 360, 361, 371, 373, 376, 378, 390, 391, 407, 408, 423, 424, 425, 433, 434, 439, 443, 447, 448, 451, 452, 453, 458, 459, 460, 462, 463, 466, 467, 468, 469, 470, 472, 479, 482, or 489. In additional embodiments, a patient suspected of having CLL can be identified by measuring the amounts of one or more of the following aberrant splice variants listed in Table 1: row 282, 292, 296, 302, 306, 330, 331, 343, 355, 360, 373, 378, 390, 391, 423, 424, 425, 433, 434, 439, 443, 447, 448, 451, 452, 458, 459, 460, 462, 463, 466, 468, 469, 470, 472, 479, 482, or 489. In still further embodiments, a patient suspected of having CLL can be identified by measuring the amount of one or more of the following aberrant splice variants listed in Table 1: row 282, 296, 302, 306, 330, 331, 355, 378, 390, 391, 424, 425, 433, 439, 443, 447, 448, 451, 452, 458, 459, 460, 462, 468, 469, or 472.


In other embodiments, one or more aberrant splice variants selected from rows 2, 3, 4, 7, 9, 10, 11, 13, 16, 18, 19, 20, 21, 22, 23, 24, 27, 28, 30, 31, 32, 33, 34, 37, 38, 39, 40, 41, 42, 43, 46, 47, 49, 50, 52, 53, 54, 56, 57, 58, 61, 62, 63, 64, 66, 67, 68, 71, 72, 75, 77, 78, 79, 80, 81, 82, 84, 87, 88, 89, 90, 91, 92, 94, 95, 97, 98, 99, 100, 101, 103, 104, 106, 107, 108, 109, 110, 111, 112, 113, 114, 116, 117, 119, 120, 121, 122, 123, 124, 125, 126, 127, 131, 132, 133, 134, 135, 136, 138, 139, 140, 141, 142, 143, 144, 146, 147, 150, 152, 154, 155, 156, 157, 159, 163, 164, 165, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 230, 231, 232, 233, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 247, 249, 250, 251, 252, 253, 254, 255, 256, or 257 of Table 1 can be measured in a patient suspected of having breast cancer. In additional embodiments, a patient suspected of having breast cancer can be identified by measuring the amounts of one or more of the following aberrant splice variants listed in Table 1: row 7, 8, 9, 10, 26, 48, 66, 105, 121, 135, 136, or 166. In additional embodiments, a patient suspected of having breast cancer can be identified by measuring the amounts of one or more of the following aberrant splice variants listed in Table 1: row 7, 8, 9, 10, 26, 48, 66, 105, 121, 135, or 136. In still further embodiments, a patient suspected of having breast cancer can be identified by measuring the amount of one or more of the following aberrant splice variants listed in Table 1: row 7, 9, 10, 66, 121, 135, or 136.


In further embodiments, one or more aberrant splice variants selected from rows 518, 519, 520, 521, 523, 524, 525, 526, 527, 528, 529, 531, 533, 534, 536, 537, 538, 539, 543, 544, 545, 549, 551, 552, 553, 555, 556, 557, 558, 559, 560, 561, 562, 563, 565, 567, 568, 569, 570, 572, 573, 575, 577, 578, 579, 580, 581, 582, 583, 584, 585, 588, 589, 590, 591, 593, 595, 597, 598, 599, 600, 601, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621, 623, 625, 627, 628, 629, 630, 632, 634, 635, 636, 637, 638, 640, 641, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 654, 657, 658, 659, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677, 678, 680, 682, 683, 684, 685, 686, 687, 688, 689, 690, 692, 694, 696, 697, 698, 699, 700, 701, 702, 703, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 763, 764, 765, 766, 767, 768, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, or 790 of Table 1 can be measured in a patient suspected of having melanoma. In additional embodiments, a patient suspected of having melanoma can be identified by measuring the amounts of one or more of the following aberrant splice variants listed in Table 1: row 519, 521, 522, 535, 554, 587, 594, 601, 618, 639, 654, 655, 670, 679, 680, 727, 729, or 730. In additional embodiments, a patient suspected of having melanoma can be identified by measuring the amounts of one or more of the following aberrant splice variants listed in Table 1: row 519, 521, 522, 535, 554, 587, 601, 618, 639, 654, 670, 680, 727, or 730. In still further embodiments, a patient suspected of having melanoma can be identified by measuring the amount of one or more of the following aberrant splice variants listed in Table 1: row 519, 521, 601, 618, 654, 670, 680, 727, or 730.


In some embodiments, one or more of the aberrant variants are selected from rows 21, 31, 51, 81, 118, 279, 372, 401, 426, 443, 528, 543, 545, 548 or 566 of Table 1. In certain embodiments, a patient suspected of having cancer can be identified by measuring the amount of one or more of the aberrant variants selected from 21, 31, 51, 81, 118, 279, 372, 401, 426, 443, 528, 543, 545, 548 or 566. In various embodiments the cancer may be CLL, breast cancer, or melanoma, for example.


Additional methods include predicting or monitoring the efficacy of a treatment for cancer by measuring the level of one or more aberrant splice variants in samples obtained from patients before or during the treatment. For example, a decrease in the levels of one or more aberrant splice variants over the course of treatment may indicate that the treatment is effective. In other cases, the absence of a decrease or an increase in the levels of one or more aberrant splice variants over the course of treatment may indicate that the treatment is not effective and should be adjusted, supplemented, or terminated. In some embodiments, the splice variants are used to track and adjust individual patient treatment effectiveness.


Embodiments of the invention also encompass methods of stratifying cancer patients into different categories based on the presence or absence of one or more particular splice variants in patient samples or the detection of one or more particular splice variants at levels that are elevated or reduced relative to those in normal cell samples. Categories may be different prognostic categories, categories of patients with varying rates of recurrence, categories of patients that respond to treatment and those that do not, and categories of patients that may have particular negative side effects, and the like. According to the categories in which individual patients fall, optimal treatments may then be selected for those patients, or particular patients may be selected for clinical trials.


Embodiments also encompass methods of distinguishing cancerous cells with SF3B1 neomorphic mutations from normal cells by using the splice variants disclosed herein as markers. Such methods may be employed, for example, to assess the growth or loss of cancerous cells and to identify cancerous cells to be treated or removed. In some embodiments, the splice variants are measured in cancerous tissue having cells with a neomorphic SF3B1 mutation before and after anti-cancer treatment, for the purpose of monitoring the effect of the treatment on cancer progression.


In additional embodiments, administering an SF3B1 modulator to a cell, such as a cancer cell, can alter the differential expression of splice variants. Accordingly, the change in expression of one or more splice variants can be used to evaluate the effect of the SF3B1 modulator on the SF3B1 protein. In one embodiment, the effect of an SF3B1 modulator on a CLL cell is evaluated by applying an SF3B1 modulator to such a cell, then detecting or quantifying one or more of the splice variants in Table 1. In additional embodiments the one or more splice variants are chosen from rows 258-516 of Table 1. In further embodiments, the one or more splice variants are chosen from rows 260, 262, 263, 265, 266, 267, 272, 273, 275, 276, 277, 279, 281, 282, 286, 287, 288, 290, 294, 295, 296, 298, 299, 301, 302, 304, 305, 306, 308, 310, 312, 313, 315, 316, 318, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 335, 337, 339, 342, 346, 348, 349, 350, 352, 353, 354, 355, 356, 357, 358, 362, 363, 365, 366, 368, 369, 370, 372, 375, 377, 378, 379, 380, 381, 382, 383, 384, 387, 388, 389, 390, 391, 392, 393, 394, 397, 398, 400, 402, 403, 404, 405, 406, 413, 415, 416, 417, 419, 420, 421, 424, 425, 428, 429, 430, 431, 432, 433, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 454, 455, 456, 458, 459, 460, 461, 462, 464, 465, 468, 469, 471, 472, 473, 474, 475, 476, 477, 478, 480, 481, 483, 484, 485, 486, 487, 488, 490, 491, 494, 496, 497, 498, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 513, 514, 515, or 516 of Table 1. In further embodiments, the one or more splice variants are chosen from rows 259, 269, 270, 271, 274, 278, 280, 282, 292, 296, 297, 302, 306, 330, 331, 333, 343, 347, 355, 360, 361, 371, 373, 376, 378, 390, 391, 407, 408, 423, 424, 425, 433, 434, 439, 443, 447, 448, 451, 452, 453, 458, 459, 460, 462, 463, 466, 467, 468, 469, 470, 472, 479, 482, or 489. In additional embodiments, the one or more splice variants are chosen from rows 282, 292, 296, 302, 306, 330, 331, 343, 355, 360, 373, 378, 390, 391, 423, 424, 425, 433, 434, 439, 443, 447, 448, 451, 452, 458, 459, 460, 462, 463, 466, 468, 469, 470, 472, 479, 482, or 489 of Table 1. In still further embodiments, the one or more splice variants are chosen from rows 282, 296, 302, 306, 330, 331, 355, 378, 390, 391, 424, 425, 433, 439, 443, 447, 448, 451, 452, 458, 459, 460, 462, 468, 469, or 472 of Table 1.


In certain embodiments, the effect of an SF3B1 modulator on a breast cancer cell is evaluated by applying an SF3B1 modulator to such a cell, then detecting or quantifying one or more of the splice variants in Table 1. In additional embodiments the one or more splice variants are chosen from rows 1-257 of Table 1. In further embodiments, the one or more splice variants are chosen from rows 2, 3, 4, 7, 9, 10, 11, 13, 16, 18, 19, 20, 21, 22, 23, 24, 27, 28, 30, 31, 32, 33, 34, 37, 38, 39, 40, 41, 42, 43, 46, 47, 49, 50, 52, 53, 54, 56, 57, 58, 61, 62, 63, 64, 66, 67, 68, 71, 72, 75, 77, 78, 79, 80, 81, 82, 84, 87, 88, 89, 90, 91, 92, 94, 95, 97, 98, 99, 100, 101, 103, 104, 106, 107, 108, 109, 110, 111, 112, 113, 114, 116, 117, 119, 120, 121, 122, 123, 124, 125, 126, 127, 131, 132, 133, 134, 135, 136, 138, 139, 140, 141, 142, 143, 144, 146, 147, 150, 152, 154, 155, 156, 157, 159, 163, 164, 165, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 230, 231, 232, 233, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 247, 249, 250, 251, 252, 253, 254, 255, 256, or 257 of Table 1. In additional embodiments, the one or more splice variants are chosen from rows 7, 8, 9, 10, 26, 48, 66, 105, 121, 135, 136, or 166 of Table 1. In further embodiments, the one or more splice variants are chosen from rows 7, 8, 9, 10, 26, 48, 66, 105, 121, 135, or 136 of Table 1. In still further embodiments, the one or more splice variants are chosen from rows 7, 9, 10, 66, 121, 135, or 136 of Table 1.


In a further embodiment, the effect of an SF3B1 modulator on a melanoma cell is evaluated by applying an SF3B1 modulator to such a cell, then detecting or quantifying one or more of the splice variants in Table 1. In additional embodiments the one or more splice variants are chosen from rows 517-790 of Table 1. In further embodiments, the one or more splice variants are chosen from rows 518, 519, 520, 521, 523, 524, 525, 526, 527, 528, 529, 531, 533, 534, 536, 537, 538, 539, 543, 544, 545, 549, 551, 552, 553, 555, 556, 557, 558, 559, 560, 561, 562, 563, 565, 567, 568, 569, 570, 572, 573, 575, 577, 578, 579, 580, 581, 582, 583, 584, 585, 588, 589, 590, 591, 593, 595, 597, 598, 599, 600, 601, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621, 623, 625, 627, 628, 629, 630, 632, 634, 635, 636, 637, 638, 640, 641, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 654, 657, 658, 659, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677, 678, 680, 682, 683, 684, 685, 686, 687, 688, 689, 690, 692, 694, 696, 697, 698, 699, 700, 701, 702, 703, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 763, 764, 765, 766, 767, 768, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, or 790 of Table 1. In still further embodiments, the one or more splice variants are chosen from rows 519, 521, 522, 535, 554, 587, 594, 601, 618, 639, 654, 655, 670, 679, 680, 727, 729, or 730 of Table 1. In additional embodiments, the one or more splice variants are chosen from rows 519, 521, 522, 535, 554, 587, 601, 618, 639, 654, 670, 680, 727, or 730 of Table 1. In still further embodiments, the one or more splice variants are chosen from rows 519, 521, 601, 618, 654, 670, 680, 727, or 730 of Table 1.


In some embodiments, the effect of an SF3B1 modulator on a cancer cell is evaluated by applying an SF3B1 modulator to such a cell, then detecting or quantifying one or more of the aberrant variants selected from rows 21, 31, 51, 81, 118, 279, 372, 401, 426, 443, 528, 543, 545, 548 or 566 of Table 1. In various embodiments, the cancer cell may be a CLL cell, a breast cancer cell, or a melanoma cell, for example.


The specific splice variants that are useful for demonstrating the effect of an SF3B1 modulator on one type of cancer cell may not be useful for demonstrating an effect of the modulator on another type of cancer cell. Aberrant splice variants that are appropriate for revealing such effects in particular cancer cells will be apparent from the description and examples provided herein.


In some embodiments, aberrant splice variants that are present at elevated levels in a cell having a neomorphic SF3B1 protein are used as markers. In other embodiments, splice variants that have reduced levels in a cell having a neomorphic SF3B1 protein are used as markers. In some embodiments, more than one splice variant will be measured. When more than one splice variant is used, they may all have elevated levels, all have reduced levels, or a mixture of splice variants with elevated and reduced levels may be used. In certain embodiments of the methods described herein, more than one aberrant splice variant is measured. In other embodiments, at least one aberrant and at least one canonical splice variant is measured. In some cases, both an aberrant and canonical splice variant associated with a particular genomic location will be measured. In other circumstances, a measured canonical splice variant will be at a different genomic location from the measured aberrant splice variant(s).


Before performing an assay for splice variants in a cell, one may determine whether the cell has a mutant SF3B1 protein. In certain embodiments, the assay for splice variants is performed if the cell has been determined to have a neomorphic SF3B1 mutant protein.


Samples


Cell samples can be obtained from a variety of biological sources. Exemplary cell samples include but are not limited to a cell culture, a cell line, a tissue, oral tissue, gastrointestinal tissue, an organ, an organelle, a biological fluid, a blood sample, a urine sample, a skin sample, and the like. Blood samples may be whole blood, partially purified blood, or a fraction of whole or partially purified blood, such as peripheral blood mononucleated cells (PBMCs). The source of a cell sample may be a solid tissue sample such as a tissue biopsy. Tissue biopsy samples may be biopsies from breast tissue, skin, lung, or lymph nodes. Samples may be samples of bone marrow, including bone marrow aspirates and bone marrow biopsies.


In certain embodiments, the cells are human cells. Cells may be cancer cells, for example hematological cancer cells or solid tumor cells. Hematological cancers include chronic lymphocytic leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia, chronic myelomonocytic leukemia, acute monocytic leukemia, Hodgkin's lymphoma, Non-Hodgkin's lymphoma, and multiple myeloma. Solid tumors include carcinomas, such as adenocarcinomas, and may be selected from breast, lung, liver, prostate, pancreatic, colon, colorectal, skin, ovarian, uterine, cervical, or renal cancers. Cell samples may be obtained directly from a patient or derived from cells obtained from a patient, such as cultured cells derived from a biological fluid or tissue sample. Samples may be archived samples, such as kryopreserved samples, of cells obtained directly from a subject or of cells derived from cells obtained from a patient.


In certain embodiments, cells are obtained from patients suspected of having cancer. The patients may show signs and symptoms of cancer, such as one or more common symptoms of CLL, which include enlarged lymph nodes, liver, or spleen, higher-than-normal white blood cell counts, recurring infections, loss of appetite or early satiety, abnormal bruising, fatigue, and night sweats. In additional embodiments, the cells have a mutant SF3B1 protein.


Cell samples described herein may be used in any of the methods presently disclosed.


Detection of Splice Variants


Certain embodiments of the methods described herein involve detection or quantification of splice variants. A variety of methods exists for detecting and quantifying nucleic acids, and each may be adapted for detection of splice variants in the described embodiments. Exemplary methods include an assay to quantify nucleic acid such as nucleic acid barcoding, nanoparticle probes, in situ hybridization, microarray, nucleic acid sequencing, and PCR-based methods, including real-time PCR (RT-PCR).


Nucleic acid assays utilizing barcoding technology such as NanoString® assays (NanoString Technologies) may be performed, for example, as described in U.S. Pat. No. 8,519,115; U.S. Pat. No. 7,919,237; and in Kulkarni, M. M., 2011, “Digital Multiplexed Gene Expression Analysis Using the NanoString nCounter System.” Current Protocols in Molecular Biology, 94:25B.10.1-25B.10.17. In an exemplary assay, a pair of probes is used to detect a particular nucleotide sequence of interest, such as a particular splice variant of interest. The probe pair consists of a capture probe and a reporter probe and that each include a sequence of from about 35 to 50 bases in length that is specific for a target sequence. The capture probe includes an affinity label such as biotin at its 3′ end that provides a molecular handle for surface-attachment of target mRNAs for digital detection, and the reporter probe includes a unique color code at its 5′ end that provides molecular barcoding of the hybridized mRNA target sequence. Capture and reporter probe pairs are hybridized to target mRNA in solution, and after excess probes are removed, the target mRNA-probe complexes are immobilized in an nCounter® cartridge. A digital analyzer acquires direct images of the surface of the cartridge to detect color codes corresponding to specific mRNA splice variant sequences. The number of times a color-coded barcode for a particular splice variant is detected reflects the levels of a particular splice variant in the mRNA library. For the detection of splice variants, either the capture or the reporter probe may span a given splice variant's exon-exon or intron-exon junction. In other embodiments, one or both of the capture and reporter probes' target sequences correspond to the terminal sequences of two exons at an exon-exon junction or to the terminal sequences of an intron and an exon at an intron-exon junction, whereby one probe extends to the exon-exon or intron-exon junction, but does not span the junction, and the other probe binds a sequence that begins on opposite side of the junction and extends into the respective exon or intron.


In exemplary PCR-based methods, a particular splice variant may be detected by specifically amplifying a sequence that contains the splice variant. For example, the method may employ a first primer specifically designed to hybridize to a first portion of the splice variant, where the splice variant is a sequence that spans an exon-exon or intron-exon junction at which alternative splicing occurs. The method may further employ a second opposing primer that hybridizes to a segment of the PCR extension product of the first primer that corresponds to another sequence in the gene, such as a sequence at an upstream or downstream location. The PCR detection method may be quantitative (or real-time) PCR. In some embodiments of quantitative PCR, an amplified PCR product is detected using a nucleic acid probe, wherein the probe may contain one or more detectable labels. In certain quantitative PCR methods, the amount of a splice variant of interest is determined by detecting and comparing levels of the splice variant to an appropriate internal control.


Exemplary methods for detecting splice variants using an in situ hybridization assay such as RNAscope® (Advanced Cell Diagnostics) include those described by Wang, F., et al., “RNAscope: a novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues,” J. Mol. Diagn. 2012 January; 14(1):22-9. RNAscope® assays may be used to detect splice variants by designing a pair of probes that targets a given splice variant, and are hybridized to target RNA in fixed and permeabilized cells. Target probes are designed to hybridize as pairs which, when hybridized to the target sequence, create a binding site for a preamplifier nucleic acid. The preamplifier nucleic acid, in turn, harbors multiple binding sites for amplifier nucleic acids, which in turn contain multiple binding sites for a labeled probe carrying a chromogenic or fluorescent molecule. In some embodiments, one of the RNAscope® target probes spans a given splice variant's exon-exon or intron-exon junction. In other embodiments, the target probes' target sequences correspond to the terminal sequences of two exons at an exon-exon junction or to the terminal sequences of an intron and an exon at an intron-exon junction, whereby one probe in the target probe pair extends to the exon-exon or intron-exon junction, but does not span the junction, and the other probe binds a sequence beginning on opposite side of the junction and extending into the respective exon or intron.


Exemplary methods for detecting splice variants using nanoparticle probes such as SmartFlare™ (Millipore) include those described in Seferos et al., “Nano-flares: Probes for Transfection and mRNA Detection in Living Cells,” J. Am. Chem. Soc. 129(50):15477-15479 (2007) and Prigodich, A. E., et al., “Multiplexed Nanoflares: mRNA Detection in Live Cells,” Anal. Chem. 84(4):2062-2066 (2012). SmartFlare™ detection probes may be used to detect splice variants by generating gold nanoparticles that are modified with one or more nucleic acids that include nucleotide recognition sequences that (1) are each complementary to a particular splice variant to be detected and (2) are each hybridized to a complementary fluorophore-labeled reporter nucleic acid. Upon uptake of the probe by a cell, a target splice variant sequence may hybridize to the one or more nucleotide recognition sequences and displace the fluorophore-labeled reporter nucleic acid. The fluorophore-labeled reporter nucleic acid, whose fluorophore had been quenched due to proximity to the gold nanoparticle surface, is then liberated from the gold nanoparticle, and the fluorophore may then be detected when free of the quenching effect of the nanoparticle. In some embodiments, nucleotide recognition sequences in the probes recognize a sequence that spans a given splice variant's exon-exon or intron-exon junction. In some embodiments, nucleotide recognition sequences in the probes recognize a sequence that is only on one side of the splice variant's exon-exon or intron-exon junction, including a sequence that terminates at the junction and a sequence that terminates one or more nucleotides away from the junction.


Exemplary methods for detecting splice variants using nucleic acid sequencing include RNA sequencing (RNA-Seq) described in Ren, S. et al. “RNA-Seq analysis of prostate cancer in the Chinese population identifies recurrent gene fusions, cancer-associated long noncoding RNAs and aberrant alternative splicings.” Cell Res 22, 806-821, doi:10.1038/cr.2012.30 (2012); and van Dijk et al., “Ten years of next-generation sequencing technology.” Trends Genet 30(9):418-26 (2014). In some embodiments, high-throughput sequencing, such as next-generation sequencing (NGS) technologies, may be used to dected splice variants. For example, the method may employ commercial sequencing platforms available for RNA-Seq, such as, e.g., Illumina, SOLID, Ion Torrent, and Roche 454. In some embodiments, the sequencing method may include pyrosequencing. For example, a sample may be mixed with sequencing enzymes and primer and exposed to a flow of one unlabeled nucleotide at a time, allowing synthesis of the complementary DNA strand. When a nucleotide is incorporated, pyrophosphate is released leading to light emission, which is monitored in real time. In some embodiments, the sequencing method may include semiconductor sequencing. For example, proton instead of pyrophosphate may be released during nucleotide incorporation and detected in real time by ion sensors. In some embodiments, the method may include sequencing with reversible terminators. For example, the synthesis reagents may include primers, DNA polymerase, and four differently labelled, reversible terminator nucleotides. After incorporation of a nucleotide, which is identified by its color, the 3′ terminator on the base and the fluorophore are removed, and the cycle is repeated. In some embodiments, the method may include sequencing by ligation. For example, a sequencing primer may be hybridized to an adapter, with the 5′ end of the primer available for ligation to an oligonucleotide hybridizing to the adjacent sequence. A mixture of octamers, in which bases 4 and 5 are encoded by one of four color labels, may compete for ligation to the primer. After color detection, the ligated octamer may be cleaved between position 5 and 6 to remove the label, and the cycle may be repeated. Thereby, in the first round, the process may determine possible identities of bases in positions 4, 5, 9, 10, 14, 15, etc. The process may be repeated, offset by one base using a shorter sequencing primer, to determine positions 3, 4, 8, 9, 13, 14, etc., until the first base in the sequencing primer is reached.


Other nucleic acid detection and analytical methods that also distinguish between splice variants of a given exon-exon or intron-exon junction in a gene by identifying the nucleotide sequence on both sides of the junction may be utilized to detect or quantify the splice variants disclosed herein. For example, splice variants of an exon-exon junction may be detected by primer extension methods in which a primer that binds to one exon is extended into the exon on the other side of the junction according to the sequence of that adjacent exon. See, for example, McCullough, R. M., et al., “High-throughput alternative splicing quantification by primer extension and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry,” Nucleic Acids Research, 2005 Jun. 20; 33(11):e99; and Milani, L., et al., “Detection of alternatively spliced transcripts in leukemia cell lines by minisequencing on microarrays,” Clin. Chem. 52: 202-211 (2006). Detection of variants on a large scale may be performed using expression microarrays that carry exon-exon or intron-exon junction probes, as described, for example, in Johnson, J. M. et al., “Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays,” Science 302: 2141-2144 (2003); and Modrek, B., et al., “Genome-wide detection of alternative splicing in expressed sequences of human genes,” Nucleic Acids Res 29: 2850-2859 (2001).


Various embodiments include reagents for detecting splice variants of the invention. In one example, reagents include NanoString® probes designed to measure the amount of one or more of the aberrant splice variants listed in Table 1. Probes for nucleic acid quantification assays such as barcoding (e.g. NanoString®), nanoparticle probes (e.g. SmartFlare™), in situ hybridization (e.g. RNAscope®), microarray, nucleic acid sequencing, and PCR-based assays may be designed as set forth above.


In these exemplary methods or in other methods for nucleic acid detection, aberrant splice variants may be identified using probes, primers, or other reagents which specifically recognize the nucleic acid sequence that is present in the aberrant splice variant but absent in the canonical splice variant. In other embodiments, the aberrant splice variant is identified by detecting the sequence that is specific to the aberrant splice variant in the context of the junction in which it occurs, i.e., the unique sequence is flanked by the sequences which are present on either side of the splice junction in the canonical splice variant. In such cases, the portion of the probe, primer, or other detection reagent that specifically recognizes its target sequence may have a length that corresponds to the length of the aberrant sequence or to or a portion of the aberrant sequence. In other embodiments, the portion of the probe, primer, or other detection reagent that specifically recognizes its target sequence may have a length that corresponds to the length of the aberrant sequence plus the length of a chosen number of nucleotides from one or both of the sequences which flank the aberrant sequence at the splice junction. Generally, the probe or primer should be designed with a sufficient length to reduce non-specific binding. Probes, primers, and other reagents that detect aberrant or canonical splice variants may be designed according to the technical features and formats of a variety of methods for detection of nucleic acids.


SF3B1 Modulators


A variety of SF3B1 modulating compounds are known in the art, and can be used in accordance with the methods described herein. In some embodiments, the SF3B1 modulating compound is a pladienolide or pladienolide analog. A “pladienolid analog” refers to a compound which is structurally related to a member of the family of natural products known as the pladienolides. Plandienolides were first identified in the bacteria Streptomyces platensis (Sakai, Takashi; Sameshima, Tomohiro; Matsufuji, Motoko; Kawamura, Naoto; Dobashi, Kazuyuki; Mizui, Yoshiharu. “Pladienolides, New Substances from Culture of Streptomyces platensis Mer-11107. I. Taxonomy, Fermentation, Isolation and Screening.” The Journal of Antibiotics. 2004, Vol. 57, No. 3). One of these compounds, pladienolide B, targets the SF3B spliceosome to inhibit splicing and alter the pattern of gene expression (Kotake et al., “Splicing factor SF3b as a target of the antitumor natural product pladienolide”, Nature Chemical Biology 3:570-575 [2007]). Certain pladienolide B analogs are described in WO 2002/060890; WO 2004/011459; WO 2004/011661; WO 2004/050890; WO 2005/052152; WO 2006/009276; and WO 2008/126918.


U.S. Pat. Nos. 7,884,128 and 7,816,401, both entitled “Process for Total Synthesis of Pladienolide B and Pladienolide D,” describe methods for synthesizing pladienolide B and D. Synthesis of pladienolide B and D may also be performed using methods described in Kanada et al., “Total Synthesis of the Potent Antitumor Macrolides Pladienolide B and D,” Angew. Chem. Int. Ed. 46:4350-4355 (2007). Kanada et al., U.S. Pat. No. 7,550,503, and International Publication No. WO 2003/099813 (WO '813), entitled “Novel Physiologically Active Substances,” describe methods for synthesizing E7107 (Compound 45 of WO '813) from pladienolide D (11107D of WO '813). In some embodiments, the SF3B1 modulator is pladienolide B. In other embodiments, the SF3B1 modulator is pladienolide D. In further embodiments, the SF3B1 modulator is E7107.


In some embodiments, the SF3B1 modulator is a compound described in U.S. application Ser. No. 14/710,687, filed May 13, 2015, which is incorporated herein by reference in its entirety. In some embodiments, the SF3B1 modulating compound is a compound having one of formulas 1-4 as set forth in Table 2. Table 2. Exemplary SF3B1 modulating compounds.












Compound Structure


















embedded image


1







embedded image


2







embedded image


3







embedded image


4









The methods described herein may be used to evaluate known and novel SF3B1 modulating compounds.


Methods of Treatment


Various embodiments of the invention include treating a patient diagnosed with cancer using an SF3B1 modulator. In certain instances, cancer cells from the patient have been determined to have a mutant SF3B1 protein. Specific SF3B1 mutants include E622D, E622K, E622Q, E622V, Y623C, Y623H, Y623S, R625C, R625G, R625H, R625L, R625P, R625S, N626D, N626H, N626I, N626S, N626Y, H662D, H662L, H662Q, H662R, H662Y, T663I, T663P, K666E, K666M, K666N, K666Q, K666R, K666S, K666T, K700E, V701A, V701F, V701I, I704F, I704N, I704S, I704V, G740E, G740K, G740R, G740V, K741N, K741Q, K741T, G742D, D781E, D781G, or D781N. In certain embodiments, SF3B1 mutants are chosen from K700E, K666N, R625C, G742D, R625H, E622D, H662Q, K666T, K666E, K666R, G740E, Y623C, T663I, K741N, N626Y, T663P, H662R, G740V, D781E, or R625L. In additional embodiments, the cancer cells have been tested to measure the amount of one or more splice variants selected from Table 1. Specific splice variants associated with neomorphic SF3B1 mutations are shown in Table 1 and described in the section on splice variants above.


In certain embodiments, a cancer patient determined to have a mutant SF3B1 protein is treated with an SF3B1 modulator as described in U.S. application Ser. No. 14/710,687, filed May 13, 2015.


EXAMPLES
Example 1: SF3B1 Mutations Induce Abnormal Splicing in a Lineage-Specific Manner

To investigate splicing alterations associated with SF3B1 mutations (“SF3B1MUT”) across multiple tumor types, an RNA-Seq quantification and differential splicing pipeline was developed and used to analyze RNA-Seq profiles from the following samples:

    • all SF3B1MUT samples in The Cancer Genome Atlas (TCGA; from 81 patients in all, representing 16 cancer types), and 40 wild type SF3B1 (SF3B1WT) samples from each of the breast cancer (20) and melanoma (20) cohorts in TCGA,
    • seven SF3B1MUT and seven SF3B1WT CLL patient samples obtained from the Lymphoma/Myeloma Service in the Division of Hematology/Oncology at the New York Weill Cornell Medical Center.


RNA-Seq Quantification Methods


Splice junctions were quantified directly from alignments (BAM files) to facilitate discovery of unannotated splice variants. For internally generated RNA-Seq data, reads were aligned to the human reference genome hg19 (GRCh37) by MapSplice and quantified by RSEM against the TCGA GAF 2.1 isoform and gene definition, emulating the TCGA “RNASeqV2” pipeline (see https://cghub.ucsc.edu/docs/tcga/UNC_mRNAseq_summary.pdf). Splice junction counts generated by MapSplice were used for downstream processing. For TCGA RNA-Seq data, comprehensive splice junction counts generated by MapSplice were not available; instead TCGA “Level 3” splice junction data reports mapped read counts for a predefined set of splice junctions from reference transcriptomes. To reconstruct genome-wide splice junction counts comparable to internally-generated RNA-Seq samples, raw RNA-Seq alignments (BAM files) were obtained from CGHub (https://cghub.ucsc.edu/) and any reads that span across a potential splice junction were directly counted. RSEM-estimated gene expression read counts were gathered directly from the TCGA RNA-SeqV2 Level 3 data matrices.


Because MapSplice only provides exon-exon junction counts, estimates of read counts spanning each intron-exon junction were required for identification of intron-retention splice variants. For every splice junction in each BAM file, reads with at least a 3-bp overhang across each of the 3′ and 5′ intron-exon junctions were counted.


For all manipulation of spliced reads within BAM files, a custom Python module “splicedbam” (available at https://github.com/h3biomed/splicedbam) was used, which uses the “pysam” extension of samtools (Li, H., et al., “The Sequence Alignment/Map format and SAMtools.” Bioinformatics, 2009 Aug. 15; 25(16):2078-9).


In some instances, splice junctions had very low counts, occasionally due to sequencing and alignment errors. Therefore, only splice junctions that had at least a total of 10 counts on average from either SF3B1WT or SF3B11T cohorts were included in downstream analyses.


Differential Splicing Detection Methods


In order to detect differential usage of a splice variant in one cohort relative to another, independent of gene expression changes and pre-defined alternative splicing models, a computational differential splicing pipeline was developed that converts splice junction counts into percentages of junction usage at splice sites with multiple possible junctions. The percentage of junction usage is a measurement of the occurrence of one splice variant relative to all other splice variants that share the same splice site. For instance, a splice variant with an alternative 3′ splice site must share its 5′ splice site with another splice variant. Therefore, for each shared splice site, the raw counts of each splice variant were divided by the total counts of all splice variants that utilize the shared splice site in order to derive a ratio. This ratio was then multiplied by 100 to convert it to a percentage. For each sample, the sum of all of the percentages of splice variants that share the same splice site will equal 100. The transformation of raw counts of each splice variant into a percentage of all splice variants sharing a splice site is itself a normalization to reduce the effect of gene expression changes. The percentages for canonical and aberrant junctions are listed in Table 1 as “Avg WT %” and “Avg Ab. %,” respectively. Differences between these percentages were assessed for statistical significance by using the moderated t-test defined in the Bioconductor's limma package (available at http://www.bioconductor.org). The statistical p-values were corrected into q values using the Benjamini-Hochberg procedure, and listed as “FDR Q-Values” in Table 1. Any splice variant that satisfied a q value of less than or equal to 0.05 was considered statistically significant.


The conversion of raw junction counts into percentage junction usage can introduce noise in some instances, i.e., when a gene in which a splice variant occurs is expressed in one cohort but has very low expression or is not expressed at all in another cohort. To address this, an additional filtering step was introduced. For each up-regulated splice variant in an SF3B1MUT sample that satisfies the above q value threshold, its corresponding canonical splice variant must be down-regulated in the SF3B1MUT sample and also must also satisfy the q value threshold for the up-regulated splice variant to be considered an aberrant splice variant.


Identification of Aberrant Splice Variants in Neomorphic SF3B1MUT Patient Samples


Initially, this framework was applied to a subset of known SF3B1MUT cancers or wild-type counterparts from The Cancer Genome Atlas (TCGA; luminal A primary breast cancer: 7 SF3B1K700E and 20 SF3B1WT; metastatic melanoma: 4 SF3B1MUT; and 20 SF3B1WT) and internally generated 7 SF3B1MUT and 7 SF3B1WT CLL patient samples. This analysis revealed 626 aberrant splice junctions to be significantly upregulated in SF3B1MUT compared to SF3B1WT. The vast majority of aberrant splicing events use an alternative 3′ss (see Table 1, “Event” column).


The computational screening of aberrant splicing events revealed a pattern of tumor-specific splicing events in breast cancer, melanoma and CLL in neomorphic SF3B1MUT samples (Table 1). In addition, a set of tumor-non-specific events (i.e., splicing events found in at least two tumor types) was observed. Some splice variants of genes with tumor-specific splicing events occur in genes with higher mRNA expression, indicating that some of the observed tumor-specific splicing results from gene expression differences (FIG. 2).


To characterize the effect of aberrant splicing in all SF3B1 variants across cancer types, RNA-Seq data for the remaining 70 SF3B1MUT patients from 14 cancer types in TCGA were quantified, and an unsupervised clustering analysis was done using all 136 samples. This clustering separated splicing events associated with neomorphic SF3B1 mutants from those associated with wild-type SF3B1 or non-neomorphic SF3B1 mutants. For example, splicing patterns associated with neomorphic SF3B1 mutants were observed in breast cancer (SF3B1K666E, SF3B1N626D), lung adenocarcinoma (SF3B1K741N, SF3B1G740V), and bladder cancer (SF3B1R625C) patient samples, as splicing events in these samples clustered with those in SF3B1K700E neomorphic samples, whereas the splicing profiles for other SF3B1 mutant samples were similar to those of SF3B1WT samples of the same tumor type. A listing of SF3B1 mutants whose splicing profiles clustered with those of neomorphic SF3B1 mutants is provided in Table 3, column 1. Additional SF3B1 mutations that are predicted to be neomorphic are listed in Table 3, column 2. A schematic diagram showing the locations of all mutations provided in Table 3 is shown in FIG. 3.









TABLE 3







Select SF3B1 mutations










SF3B1 Mutations with Splicing Profiles




Clustering with Neomorphic
Predicted Neomorphic



SF3B1 Mutations
SF3B1 Mutations







K700E
K666Q



K666N
K666M



R625C
H662D



G742D
D781G



R625H
I704F



E622D
I704N



H662Q
V701F



K666T
R625P



K666E
R625G



K666R
N626D



G740E
H662Y



Y623C
N626S



T663I
G740R



K741N
N626I



N626Y
N626H



T663P
V701I



H662R
R625S



G740V
K741T



D781E
K741Q



R625L
I704V




I704S




E622V




Y623S




Y623H




V701A




K666S




H662L




G740K




E622Q




E622K




D781N










Example 2: Validation of Aberrant Splice Variants in Cell Lines

Aberrant splicing in cell line models was analyzed by collecting RNA-Seq profiles for a panel of cell lines with endogenous SF3B1 neomorphic mutations (pancreatic adenocarcinoma Panc 05.04: SF3B1Q699H/K700E double mutant; metastatic melanoma Colo829: SF3B1P718L; and lung cancer NCI-H358: SF3B1A745V; obtained from the American Type Culture Collection [ATCC] or RIKEN BioResource Center and cultured as instructed) and from several SF3B1WT cell lines from either the same tumor types (pancreatic adenocarcinoma Panc 10.05, HPAF-II, MIAPaCa-2, Panc04.03, PK-59, lung cancer NCI-H358, NCI-H1792, NCI-H1650, NCI-H1975, NCI H1838) or normal control cells of the same patient (Epstein-Barr virus [EBV]-transformed B lymphoblast colo829BL). RNA-Seq profiles were also collected from isogenic pre B-cell lines (Nalm-6) engineered via AAV-mediated homology to express SF3B1K700E (Nalm-6 SF3B1K700E) or a synonymous mutation (Nalm-6 SF3B1K700K). The isogenic cell lines Nalm-6 SF3B1K700E and Nalm-6 SF3B1K700K generated at Horizon Discovery, were cultured in presence of Geneticin (0.7 mg/ml, Life Technologies) for selection. All RNA-Seq analysis was performed using the same pipeline described for patient samples in Example 1. Unsupervised clustering of cell lines using the aberrant splice junctions identified in patients resulted in clear segregation of Panc 05.04 and Nalm-6 SF3B1K700E from wild-type and other SF3B1-mutant cells.


A NanoString® assay was developed to quantify aberrant and canonical splice variants and was validated using the same cell panel. For the NanoString® assay, 750 ng of purified total RNA was used as template for the nCounter® (NanoString Technologies®) expression assay using a custom panel of NanoString® probes. The sample preparation was set up as recommended (NanoString® Technologies protocol no. C-0003-02) for an overnight hybridization at 65° C. The following day, samples were processed through the automated nCounter® Analysis System Prep Station using the high sensitivity protocol (NanoString® Technologies protocol no. MAN-00029-05) followed by processing through the nCounter® Analysis System Digital Analyzer (protocol no. MAN-00021-01) using 1150 FOVs for detection. Data was downloaded and analyzed for quality control metrics and normalization using the nSolver™ Analysis Software (NanoString Technologies®). The data was first normalized for lane-to-lane variation using the positive assay controls provided by the manufacturer (NanoString® positive controls A-F [containing in vitro transcribed RNA transcripts at concentrations of 128 fM, 32 fM, 8 fM, 2 fM, 0.5 fM, and 0.125 fM, each pre-mixed with NanoString® Reporter CodeSet probes])). Any samples with normalization factors <0.3 and >3 were not considered for further analysis. This was followed by content normalization using the geo-mean of GAPDH, EEF1A1 and RPLP0. All samples were within the recommended 0.1-10 normalization factor range. Each normalized value was then checked to ensure that it was at least two standard deviations higher than the average of background signal recorded for that lane. Any value below that was considered below detection limit. These normalized values were taken for further bioinformatics and statistical analysis.


As observed in the RNA-Seq analysis, only the Panc 05.04 and isogenic Nalm-6 SF3B1K700E cell lines showed clear presence of aberrant splicing (FIG. 4).


Analysis of SF3B1 Mutant SF3B1Q699H


The Panc 05.04 cell line carries the neomorphic mutation SF3B1K700E and an additional mutation at position 699 (SF3B1Q699H). To evaluate the functional relevance of this second mutation, SF3B1Q699H and SF3B1K700E mutant SF3B1 proteins were expressed alone or in combination in 293FT cells (FIG. 5) for analysis of RNA by NanoString®. To express the mutants in 293FT cells, mammalian expression plasmids were generated using the Gateway technology (Life Technologies). First, the HA-tag mxSF3B1 wild-type (Yokoi, A. et al. “Biological validation that SF3b is a target of the antitumor macrolide pladienolide.” FEBS J. 278:4870-4880 [2011]) was cloned by PCR into the pDONR221, then the mutations were introduced using the site-directed mutagenesis kit (QuikChange II XL, Agilent). LR reaction was performed to clone all the HA-tag mxSF3B1 wild-type and mutants into the pcDNA-DEST40 (Life Technologies). 293FT cells (Life Technologies), cultured according to the manufacturer's instructions, were seeded on 6 wells/plate and transfected with generated plasmid using Fugene (Roche). One μg of DNA per pcDNA-DEST40 HA-mxSF3B1 construct was used for each transient transfection, generated in triplicates. Forty-eight hours after transfection, cells were collected to isolate protein and RNA for western blot and NanoString® analysis, respectively. Protein extracts were prepared by lysing the cells with RIPA (Boston BioProducts). Twenty-three μg of protein was loaded in a SDS-PAGE gel and identified using SF3B1 antibody (a-SAP 155, MBL) and anti-GAPDH (Sigma). Li-Cor donkey-anti-mouse 800CW and Li-Cor donkey-anti-rabbit 800CW were used as secondary antibodies and detected by Odyssey imager (Li-Cor). RNA was isolated from the cells and retrotranscribed using MagMax for Microarray and Superscript VILO II (Life Technologies), respectively, according to the manufacturer manual, and then analyzed with the NanoString® assay.


Expression of SF3B1K700E and SF3B1Q699H/K700E induced aberrant splicing, whereas SF3B1Q699H alone or SF3B1A745V or SF3B1R1074H (a substitution conferring resistance to the spliceosome inhibitor pladienolide B) did not induce aberrant splicing (FIG. 6), indicating that SF3B1Q999H is a non-functional substitution.


These data confirm that Panc 05.04 and Nalm-6 SF3B1K700E isogenic cells are representative models to study the functional activity of SF3B1 neomorphic mutations and the activity of splicing inhibitors in vitro and in vivo.


Example 3: Neomorphic SF3B1 Mutations Induce Abnormal mRNA Splicing

The functional activity of neomorphic mutations found in SF3B1MUT cancers was analyzed by expressing SF3B1WT, neomorphic SF3B1 mutants, or SF3B1K700R (the mutation observed in a renal clear cell carcinoma patient that clusters with SF3B1WT patients) in 293FT cells and determining splicing aberrations by NanoString®. The expression of all constructs was confirmed by western blot (FIG. 7). All SF3B1 neomorphic mutations tested demonstrated the same usage of alternative splice sites observed in patient samples (“MUT isoform” in FIG. 8), but SF3B1K700R and SF3B1WT did not show aberrant splicing (FIG. 8). Moreover, the expression of none of the SF3B1 constructs changed the overall gene expression (“PAN-gene” in FIG. 8) or the canonical splice isoforms (“WT isoform” in FIG. 8). This indicated both a correlation between the presence of the neomorphic SF3B1 mutations and alternative splicing as well as similar functional activity of the different neomorphic mutations, as was indicated by the RNA-Seq analysis of patient samples.


The correlation between the SF3B1K700E neomorphic mutation and aberrant splicing was analyzed using tetracycline-inducible shRNA to selectively knockdown the neomorphic SF3B1 mutant or SF3B1WT allele in Panc 05.04 and Panc 10.05 cell lines (neomorphic SF3B1MUT and SF3B1WT cell lines, respectively; obtained from the American Type Culture Collection [ATCC] or from RIKEN BioResource Center and cultured as instructed).


For the knockdown experiment, virus encoding shRNA was prepared in LentiX-293T cells (Clontech), which were cultured according to the manufacturer's instruction. The inducible shRNA were cloned into AgeI and EcoRI of the pLKO-iKD-H1 euro vector. The sequences of hairpins were:











shRNA #13 SF3B1PAN







(SEQ ID NO: 1180)









GCGAGACACACTGGTATTAAG,







shRNA #8 SF3B1WT







(SEQ ID NO: 1181)









TGTGGATGAGCAGCAGAAAGT;



and







shRNA #96 SF3B1MUT







(SEQ ID NO: 1182)









GATGAGCAGCATGAAGTTCGG.






Cells were transfected with 2.4 μg of target pLKO-shRNA plasmid, plus 2.4 μg of p Δ 8.91 (packaging), and 0.6 μg VSVG (envelope) using TransIT reagent (Mirus). The virus was used to infect Panc 05.04 and Panc 10.05 by spin infection using Polybrene (Millipore). The day after infection, the cells were cultured in selecting media (1.25 μg/ml Puromycin [Life Technologies]) for 7 days to select for shRNA-expressing cells. The selected cells were cultured in the presence or absence of Doxycycline hyclate (100 ng/mL; Sigma) to induce the shRNA. Cells were harvested for protein and RNA at day 4 post-induction. In addition, cells were seeded for colony forming assay and CellTiter-Glo® assay (Promega). At day 9, cells were fixed with formaldehyde and stained with crystal violet.


To confirm SF3B1 knockdown using western blots, protein extracts were prepared by lysing the cells with RIPA (Boston BioProducts). Twenty to 25 μg of protein from each sample was separated by SDS-PAGE and transferred to nitrocellulose membranes (iblot, Life Technologies). Membranes were first blocked with Odyssey Blocking Buffer (Li-Cor) and then incubated with SF3B1 antibody (a-SAP 155, MBL) and anti-GAPDH (Sigma). Li-Cor donkey-anti-mouse 800CW and Li-Cor donkey-anti-rabbit 800CW were used as secondary antibodies and detected by Odyssey imager (Li-Cor).


To confirm SF3B1 knockdown by allele specific qPCR, RNA was isolated from the cells and retrotranscribed using MagMax for Microarray and Superscript VILO II (Life Technologies), respectively according to the manufacturer manual. qPCR was performed using ViiA7 (Life Technologies). The reaction included 20-50 ng cDNA, Power SYBR green master mix (Life Technologies) and 300 nM primers. The following primers were used:











SF3B1WT:







(SEQ ID NO: 1183)









FW 5′-GACTTCCTTCTTTATTGCCCTTC



and











(SEQ ID NO: 1184)









RW 5′-AGCACTGATGGTCCGAACTTTC,







SF3B1MUT:







(SEQ ID NO: 1185)









FW 5′-GTGTGCAAAAGCAAGAAGTCC



and











(SEQ ID NO: 1186)









RW 5′-GCACTGATGGTCCGAACTTCA,







SF3B1PAN:







(SEQ ID NO: 1187)









FW 5′-GCTTGGCGGTGGGAAAGAGAAATTG



and











(SEQ ID NO: 1188)









RW 5′-AACCAGTCATACCACCCAAAGGTGTTG,







β-actin (internal control):







(SEQ ID NO: 1189)









FW 5′-GGCACCCAGCACAATGAAGATCAAG



and











(SEQ ID NO: 1190)









RW 5′-ACTCGTCATACTCCTGCTTGCTGATC.







Biological and technical triplicates were performed.


The western blotting and allele specific PCR both confirmed knockdown of the SF3B1 alleles (FIGS. 9 and 10).


To determine the association between the expression of SF3B1 mutations and aberrant splicing, RNA isolated from the cells following doxycycline-induced knockdown was analyzed by NanoString®. In Panc 05.04, after knockdown of the neomorphic SF3B1MUT allele, the aberrant splice variants were downregulated and the canonical splice variants were upregulated, whereas the opposite was observed with selective depletion of the SF3B1WT allele (FIG. 11A), indicating that the neomorphic SF3B1MUT protein does not possess wild-type splicing activity. The expression of a pan shRNA induced the regulation of all splice variants as well as the depletion of SF3B1WT in Panc 10.05 cells (FIG. 11B). SF3B1PAN knockdown impaired growth and colony formation in both cell lines, while a minimal effect was observed with selective depletion of neomorphic SF3B1MUT in Panc05.04 cells (FIGS. 12 and 13). When the SF3B1WT allele was knocked down in Panc 05.04 cells, only a partial viability effect was observed, whereas SF3B1PAN knockdown prevented colony formation and cell proliferation (FIGS. 12 and 14), indicating that pan-inhibition of SF3B1 leads to antitumor activity in vitro and in vivo.


Example 4: Modulation of Neomorphic SF3B1MUT Splicing

Overall Effect of E7107 on Splicing


E7107 is a small-molecule compound that inhibits splicing by targeting the U2 snRNP-associated complex SF3B (Kotake, Y. et al. “Splicing factor SF3b as a target of the antitumor natural product pladienolide.” Nat Chem Biol 3, 570-575, doi:10.1038/nchembio.2007.16 [2007]). The ability of E7107 to inhibit splicing was observed in an in vitro splicing assay (IVS) using the substrate Ad2 (Pellizzoni, L., Kataoka, N., Charroux, B. & Dreyfuss, G. “A novel function for SMN, the spinal muscular atrophy disease gene product, in pre-mRNA splicing.” Cell 95, 615-624 [1998]) and nuclear extracts from the Nalm-6 isogenic cell lines or 293F cells (Life Technologies; cultured according to the manufacturer's instructions) expressing Flag-tag SF3B1WT or SF3B1K700E, as follows.


Nuclear extracts were prepared from 293F cells transfected with pFLAG-CMV-2-SF3B1 plasmids, or from isogenic Nalm-6 cells (SBH Sciences). The plasmids were generated by cloning the mxSF3B1 gene into the HindIII and KpnI sites of pFLAG-CMV2 (Sigma), and the mutations mxSF3B1K700E, mxSF3B1R1074H and mxSF3B1K700E-R1074H were introduced using the same site-directed mutagenesis kit. Cell pellets were resuspended in hypotonic buffer (10 mM HEPES pH 7.9, 1.5 mM MgCl2, 10 mM KCl, 0.2 mM PMSF, and 0.5 mM DTT; for Nalm-6 cells, 40 mM KCl was used). The suspension was brought up to a total of five packed cell volumes (PCV). After centrifugation, the supernatant was discarded, and the cells were brought up to 3 PCV with hypotonic buffer, and incubated on ice for 10 minutes. Cells were lysed using a dounce homogenizer and then centrifuged. The supernatant was discarded, and the pellet was resuspended with ½ packed nuclear volume (PNV) of low salt buffer (20 mM HEPES pH 7.9, 1.5 mM MgCl2, 20 mM KCl, 0.2 mM EDTA, 25% glycerol, 0.2 mM PMSF, 0.5 mM DTT), followed by ½ PNV of high salt buffer (same as low salt buffer except 1.4M KCl was used). The nuclei were gently mixed for 30 minutes before centrifuging. The supernatant (nuclear extract) was then dialyzed into storage buffer (20 mM HEPES pH 7.9, 100 mM KCl, 0.2 mM EDTA, 20% glycerol, 0.2 mM PMSF, 0.5 mM DTT). Protein concentration was determined using NanoDrop 8000 UV-Vis spectrophotometer (Thermo Scientific).


For in vitro splicing (IVS) reactions, an Ad2-derived sequence (Pellizzoni, L., Kataoka, N., Charroux, B. & Dreyfuss, G. “A novel function for SMN, the spinal muscular atrophy disease gene product, in pre-mRNA splicing.” Cell 95, 615-624 [1998]) was cloned into the pGEM-3Z vector (Promega) using EcoRI and XbaI restriction sites. The resulting pGEM-3Z-Ad2 plasmid was linearized using XbaI, purified, resuspended in TE buffer, and used as a DNA template in the in vitro transcription reaction. The Ad2 pre-mRNA was generated and purified using MEGAScript T7 and MegaClear kits, respectively (Invitrogen). Twenty μL splicing reactions were prepared using 80 μg nuclear extracts, 20U RNAsin Ribonuclease inhibitor (Promega), 10 ng Ad2 pre-mRNA, and varying concentrations of E7107. After a 15 minute pre-incubation, activation buffer (0.5 mM ATP, 20 mM creatine phosphate, 1.6 mM MgCl2) was added to initiate splicing, and the reactions were incubated for 90 minutes. RNA was extracted using a modified protocol from a RNeasy 96 Kit (Qiagen). The splicing reactions were quenched in 350 μL Buffer RLT Plus (Qiagen), and 1.5 volume ethanol was added. The mixture was transferred to an RNeasy 96 plate, and the samples were processed as described in the kit protocol. RNA was diluted 1/10 with dH2O. 10 μL RT-qPCR reactions were prepared using TaqMan RNA-to-CT 1-step kit (Life Technologies), 8.5 μL RNA, and 1 μL of Ad2 mRNA primers/probe set (FW 5′ ACTCTCTTCCGCATCGCTGT (SEQ ID NO: 1191), RW 5′-CCGACGGGTTTCCGATCCAA (SEQ ID NO: 1192) and probe 5′ CTGTTGGGCTCGCGGTTG (SEQ ID NO: 1193)).


To evaluate pSF3B1, in vitro splicing reactions were prepared as described above. To quench the reactions, 6× Laemmli Buffer (Boston Bioproducts) was added, and the samples were subjected to SDS-PAGE gels (Life Technologies). The separated proteins were transferred onto nitrocellulose membranes then blocked with blocking buffer (50% Odyssey Blocking Buffer (Li-Cor Biosciences) and 50% TBST). The blots were incubated with anti-SF3B1 antibody overnight, after several washes in TBST, they were incubated with IRDye 680LT donkey-α-mouse-IgG antibody and visualized using an Odyssey CLx imaging system (Li-Cor Biosciences).


E7107 was able to inhibit splicing in nuclear extracts from both the Nalm-6 cells or the 293F cells expressing Flag-tag SF3B1WT or SF3B1K700E (FIGS. 15A and 15B).


E7107 Binds Both SF3B1WT and SF3B1K700E Proteins


The ability of E7107 to bind both SF3B1WT and SF3B1K700E proteins was evaluated in a competitive binding assay using Flag-tag SF3B1 proteins immunoprecipitated with anti-Flag antibody from transiently transfected 293F cells. Batch immobilization of antibody to beads was prepared by incubating 80 μg of anti-SF3B1 antibody (MBL International) and 24 mg anti-mouse PVT SPA scintillation beads (PerkinElmer) for 30 minutes. After centrifugation, the antibody-bead mixture was resuspended in PBS supplemented with PhosSTOP phosphatase inhibitor cocktail (Roche) and complete ULTRA protease inhibitor cocktail (Roche). Nuclear extracts were prepared by diluting 40 mg into a total volume of 16 mL PBS with phosphatase and protease inhibitors, and the mixture was centrifuged. The supernatant was transferred into a clean tube, and the antibody-bead mixture was added and incubated for two hours. The beads were collected by centrifuging, washed twice with PBS+0.1% Triton X-100, and resuspended with 4.8 mL of PBS. 100 μL binding reactions were prepared using slurry and varying concentrations of E7107. After 15 minutes pre-incubation at room temperature, one nM 3H-probe molecule (described in Kotake, Y. et al. Splicing factor SF3b as a target of the antitumor natural product pladienolide. Nat Chem Biol 3, 570-575, doi:10.1038/nchembio.2007.16 [2007]) was added. The mixture was incubated at room temperature for 15 minutes, and luminescence signals were read using a MicroBeta2 Plate Counter (PerkinElmer).


As shown in FIG. 16A, E7107 was able to competitively inhibit binding of the 3H-probe molecule in a similar manner to either SF3B1WT (IC50: 13 nM) or SF3B1K700E (IC50: 11 nM).


Effect of E7107 and Other Compounds on Normal and Aberrant Splicing


E7107 was also tested in vitro in Nalm-6 isogenic cell lines for the ability to modulate normal and aberrant splicing induced by SF3B1WT and SF3B1K700E protein. Nalm-6 isogenic cells were treated with increasing concentrations of E7107 for six hours and RNA was analyzed by qPCR. As shown in FIG. 16B, canonical splicing was observed, with accumulation of pre-mRNA for EIF4A1 and downregulation of the mature mRNA SLC25A19 observed in both cell lines. Additionally, downregulation of mature mRNA of the two abnormally spliced isoforms of COASY and ZDHHC16 was observed in Nalm-6 SF3B1K700E (FIG. 16B).


To investigate the broader activity of E7107 on normal and aberrant splicing, RNA from Nalm-6 isogenic cells treated for two and six hours at 15 nM was analyzed by NanoString®. Only partial inhibition of splicing was observed at two hours in both isogenic cell lines, and at the level of gene, WT-associated isoforms, and MUT-associated isoform expression. After six hours of treatment, clear inhibition was detected for all isoforms quantified (FIG. 17). Similar results were obtained by RNA-Seq analysis of isogenic cell lines treated for six hours with E7107 at 15 nM (FIG. 18). Normal and aberrant splicing in the isogenic cell lines was also analyzed by RNA-Seq following treatment with one of additional compounds having formulas 1 or 2. Like E7107, each of these additional compounds inhibited expression of both WT-associated and MUT-associated RNA isoforms (FIG. 19; compound is indicated by formula number above each vertical pair of graphs). For the RNA-Seq analysis, cells were washed with PBS after treatment with E7107 or other test compound, and RNA was isolated using PureLink (Life Technology) as reported in the manufacturer's manual. cDNA library preparation, sequencing and raw read filtering was performed as described in Ren, S. et al. “RNA-Seq analysis of prostate cancer in the Chinese population identifies recurrent gene fusions, cancer-associated long noncoding RNAs and aberrant alternative splicings.” Cell Res 22, 806-821, doi:10.1038/cr.2012.30 (2012).


In addition, the ability of E7107 to modulate splicing was tested in mice bearing human tumor xenografts. Nalm-6 isogenic xenograft mice were generated by subcutaneously implanting 10×106 Nalm-6 isogenic cells into the flank of CB17-SCID mice, and tumors from these mice were collected at different timepoints after a single intravenous (IV) dose of E7107 (5 mg/kg) and analyzed to determine compound concentrations and splicing regulation. RNA was isolated from the tumors using RiboPure™ RNA purification kit (Ambion®) and used for NanoString® assay or qPCR. The RNA was retrotranscribed according to the instructions of the SuperScript® VILO™ cDNA synthesis kit (Invitrogen™) and 0.04 μl of cDNA was used for qPCR. qPCR for pre-mRNA EIF4A1 and mature mRNA SLC24A19 and pharmacokinetic evaluation were performed as described in Eskens, F. A. et al. “Phase I pharmacokinetic and pharmacodynamic study of the first-in-class spliceosome inhibitor E7107 in patients with advanced solid tumors.” Clin Cancer Res 19, 6296-6304, doi:10.1158/1078-0432.CCR-13-0485 (2013). The primers and probes used for ZDHHC16 were the following: FW 5′-TCTTGTCTACCTCTGGTTCCT (SEQ ID NO: 1194), RW 5′ CCTTCTTGTTGATGTGCCTTTC (SEQ ID NO: 1195) and probe 5′ FAM CAGTCTTCGCCCCTCTTTTCTTAG (SEQ ID NO: 1196). The primers and probes used for COASY were the following: FW 5′-CGGTGGTGCAAGTGGAA (SEQ ID NO: 1197), RW 5′-GCCTTGGTGTCCTCATTTCT (SEQ ID NO: 1198) and probe 5′-FAM-CTTGAGGTTTCATTTCCCCCTCCC (SEQ ID NO: 1199). E7107 reached similar drug concentrations and modulated canonical splicing (accumulation of pre-mRNA for EIF4A1 and downregulation of the mature mRNA SLC25A19) in both Nalm-6 SF3B1K700K and Nalm-6 SF3B1K700E models and downregulated abnormal splicing of COASY and ZDHHC16 in the Nalm-6 SF3B1K700E cells (FIG. 20), as observed in vitro. The canonical and aberrant splice mRNA isoforms were downregulated by E7107 as early as one hour following administration of the compound, and expression normalized shortly after treatment (FIG. 21), consistent with E7107 pharmacokinetic profile. Similar results were observed in a Panc 05.04 neomorphic SF3B1 xenograft model (FIG. 22). All these data indicate that E7107 is a pan-splicing modulator that can bind and inhibit SF3B1WT and SF3B1K700E proteins in vitro and in vivo.


Example 5: E7107 has Anti-Tumor Activity Via SF3B1 Modulation

SF3B1 modulator E7107 was tested for antitumor activity in vivo by determining the effect of E7107 in a subcutaneous model of Nalm-6 SF3B1K700E. 10×106 Nalm-6 SF3B1K700E were subcutaneously implanted into the flank of CB17-SCID mice, and mice were administered E7107 intravenously once a day for 5 consecutive days (QD×5) at three well tolerated dose levels (1.25, 2.5 and 5 mg/kg). After this dosing, the animals were monitored until they reached either of the following endpoints: 1) excessive tumor volume measured three times a week (tumor volume calculated by using the ellipsoid formula: (length×width)/2), or 2) development of any health problem such as paralysis or excessive body weight loss. Partial regression (PR) and complete regression (CR) are defined as 3 consecutive tumor measurements <50% and <30% of starting volume respectively.


In the 1.25 mg/kg group, all animals (n=10) reached complete regression (CR) in the Nalm-6 SF3B1K700E xenograft group. In the 2.5 mg/kg group, 10/10 CRs were observed in the Nalm-6 SF3B1K700E group by day 9. In the 5 mg/kg group all Nalm-6 SF3B1K700E xenograft animals reached CR as early as 9 days post treatment and had mean survival times of over 250 days (FIGS. 23 and 24). These data demonstrate antitumor activity of SF3B1 modulator in SF3B1K700E xenografts in vivo.


The ability of E7107 to inhibit splicing in CLL patient samples in vitro was determined by isolating RNA from samples of E7107-treated patient cells treated for 6 hours with E7107 at 10 nM and performing RNA-Seq analysis. To do so, cells were washed with PBS after treatment with E7107, and RNA was isolated using PureLink (Life Technology) as reported in the manufacturer's manual. cDNA library preparation, sequencing and raw read filtering was performed as described in Ren, S. et al. “RNA-Seq analysis of prostate cancer in the Chinese population identifies recurrent gene fusions, cancer-associated long noncoding RNAs and aberrant alternative splicings.” Cell Res 22, 806-821, doi:10.1038/cr.2012.30 (2012). As shown in FIG. 25, E7107 inhibited the expression of canonical splice isoforms in SF3B1WT and neomorphic SF3B1MUT patient samples. E7107 was able to modulate aberrant splicing in all CLL patient samples carrying neomorphic SF3B1 mutations.


Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims.

Claims
  • 1. A method of detecting one or more splice variants selected from rows 1-790 of Table 1 in a biological sample, comprising a) providing a biological sample suspected of containing one or more splice variants;b) contacting the biological sample with one or more nucleic acid probes capable of specifically hybridizing to the one or more splice variants, andc) detecting the binding of the one or more probes to the one or more splice variants.
  • 2. The method of claim 1, wherein the one or more nucleic acid probes each comprise a label.
  • 3. The method of claim 1, further comprising contacting the biological sample with one or more additional nucleic acid probes, wherein the additional probes are each labeled with a molecular barcode.
  • 4. A method of modulating the activity of a neomorphic mutant SF3B1 protein in a target cell, comprising applying an SF3B1-modulating compound to the target cell, wherein the target cell has been determined to express one or more aberrant splice variants selected from rows 1-790 of Table 1 at a level that is increased or decreased relative to the level in a cell not having the neomorphic mutant SF3B1 protein.
  • 5. A method for evaluating the ability of a compound to modulate the activity of a neomorphic mutant SF3B1 protein in a target cell, comprising the steps of: a) providing a target cell having a mutant SF3B1 protein;b) applying the compound to the target cell; andc) measuring the expression level of one or more splice variants selected from row 1-790 of Table 1.
  • 6. The method of claim 5, further comprising the step of measuring the expression level of one or more splice variants selected from row 1-790 of Table 1 before step (b).
  • 7. The method of any one of claims 4-6, wherein the neomorphic mutant SF3B1 protein is selected from E622D, E622K, E622Q, E622V, Y623C, Y623H, Y623S, R625C, R625G, R625H, R625L, R625P, R625S, N626D, N626H, N626I, N626S, N626Y, H662D, H662L, H662Q, H662R, H662Y, T663I, T663P, K666E, K666M, K666N, K666Q, K666R, K666S, K666T, K700E, V701A, V701F, V701I, I704F, I704N, 17045, 1704V, G740E, G740K, G740R, G740V, K741N, K741Q, K741T, G742D, D781E, D781G, or D781N.
  • 8. The method of any one of claims 5-7, wherein the step of measuring the expression level of one or more splice variants comprises using a nucleic acid quantification assay selected from nucleic acid barcoding, RT-PCR, microarray, nucleic acid sequencing, nanoparticle probes, and in situ hybridization.
  • 9. The method of any one of claims 5-8, wherein the step of measuring the expression level of one or more splice variants comprises measuring the number of copies of the one or more splice variant RNAs in the target cell.
  • 10. The method of any one of claims 4-9, wherein the compound is selected from a small molecule, an antibody, an antisense molecule, an aptamer, an RNA molecule, and a peptide.
  • 11. The method of claim 10, wherein the compound is a small molecule selected from a pladienolide or a pladienolide analog.
  • 12. The method of claim 11, wherein the pladienolide analog is selected from pladienolide B, pladienolide D, E7107, a compound of formula 1:
  • 13. The method of any one of claims 4-12, wherein the target cell is obtained from a patient suspected of having myelodysplastic syndrome, chronic lymphocytic leukemia, chronic myelomonocytic leukemia, or acute myeloid leukemia.
  • 14. The method of any one of claims 4-13, wherein the target cell is obtained from a sample selected from blood or a blood fraction or is a cultured cell derived from a cell obtained from a sample chosen from blood or a blood fraction.
  • 15. The method of claim 14, wherein the target cell is a lymphocyte.
  • 16. The method of any one of claims 4-12, wherein the target cell is obtained from a solid tumor.
  • 17. The method of claim 16, wherein the target cell is a breast tissue cell, pancreatic cell, lung cell, or skin cell.
  • 18. A method for treating a patient with a neoplastic disorder, comprising administering a therapeutically effective amount of an SF3B1-modulating compound to the patient, wherein a cell from the patient has been determined to: a) contain a neomorphic mutant SF3B1 protein; andb) express one or more aberrant splice variants selected from rows 1-790 of Table 1 at a level that is increased or decreased relative to the level in a cell not having the neomorphic mutant SF3B1 protein.
  • 19. The method of any one of claims 1-18, wherein one or more of the splice variants is an aberrant variant selected from rows 1, 7, 9, 10, 13, 15, 16, 18, 21, 24, 27, 28, 30, 31, 33, 34, 48, 51, 62, 65, 66, 71, 72, 81, 84, 89, 91, 105, 107, 121, 135, 136, 152, 178, 235, 240, 247, 265, 267, 272, 276, 279, 282, 283, 286, 292, 295, 296, 298, 302, 306, 329, 330, 331, 343, 350, 355, 356, 360, 364, 372, 378, 390, 391, 423, 424, 425, 426, 431, 433, 438, 439, 443, 445, 447, 448, 451, 452, 458, 459, 460, 462, 468, 469, 472, 500, 508, 517, 519, 521, 524, 525, 527, 528, 530, 533, 536, 540, 543, 548, 545, 554, 556, 559, 571, 573, 580, 582, 583, 597, 601, 615, 617, 618, 639, 640, 654, 657, 666, 670, 680, 727, 730, 750, 758, 767, or 774 of Table 1.
  • 20. The method of any one of claims 1-19, wherein one or more of the splice variants is an aberrant variant selected from rows 21, 31, 51, 81, 118, 279, 372, 401, 426, 443, 528, 543, 545, 548 or 566 of Table 1.
Parent Case Info

The present application claims the benefit of priority to U.S. Provisional Patent Application No. 62/212,876, filed Sep. 1, 2015, the contents of which are hereby incorporated by reference herein in their entirety.

PCT Information
Filing Document Filing Date Country Kind
PCT/US16/49490 8/30/2016 WO 00
Provisional Applications (1)
Number Date Country
62212876 Sep 2015 US