Mutation Analysis (MutSig)
Overview
Introduction

This report serves to describe the mutational landscape and properties of a given individual set, as well as rank genes and genesets according to mutational significance. MutSig v1.5 was used to generate the results found in this report.

Working with individual set: CESC.

Number of patients in set: 36

Input

The input for this pipeline is a set of individuals with the following files associated for each:

1. An annotated .maf file describing the mutations called for the respective individual, and their properties.

2. A .wig file that contains information about the coverage of the sample.

Summary

Significantly mutated genes (q ≤ 0.1): 8

Mutations seen in COSMIC: 0

Significantly mutated genes in COSMIC territory: 0

Genes with clustered mutations (&le 3 aa apart): 0

Significantly mutated genesets: 67

Significantly mutated genesets: (excluding sig. mutated genes): 19

Results
Breakdown of Mutations by Type

Table 1.  Get Full Table Table representing breakdown of mutations by type.

type count
Frame_Shift_Del 20
Frame_Shift_Ins 17
In_Frame_Del 9
In_Frame_Ins 1
Missense_Mutation 3422
Nonsense_Mutation 330
Nonstop_Mutation 7
Silent 1335
Splice_Site 60
Total 5201
Breakdown of Mutation Rates by Category Type

Table 2.  Get Full Table A breakdown of mutation rates per category discovered for this individual set.

category n N rate rate_per_mb relative_rate
(A/T)p*A->T 381 212530608 1.8e-06 1.8 0.51
(A/T)p*N->nonflip 1231 472118544 2.6e-06 2.6 0.74
(C/G)p*N->mut 1582 623521188 2.5e-06 2.5 0.72
(A/T)p*C->G 228 259587936 8.8e-07 0.88 0.25
indel+null 438 1095639768 4e-07 0.4 0.11
double_null 6 1095639768 5.5e-09 0.0055 0.0016
Total 3866 1095639768 3.5e-06 3.5 1
Target Coverage for Each Individual

The x axis represents the samples. The y axis represents the exons, one row per exon, and they are sorted by average coverage across samples. For exons with exactly the same average coverage, they are sorted next by the %GC of the exon. (The secondary sort is especially useful for the zero-coverage exons at the bottom).

Figure 1. 

Distribution of Mutation Counts, Coverage, and Mutation Rates Across Samples

Figure 2. 

Significantly Mutated Genes

Table 3.  Get Full Table A Ranked List of Significantly Mutated Genes. Number of significant genes found: 8. Number of genes displayed: 35

rank gene description N n npat nsite nsil n1 n2 n3 n4 n5 n6 p q
1 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 118332 9 7 3 0 5 0 4 0 0 0 5.4e-08 0.00098
2 NFE2L2 nuclear factor (erythroid-derived 2)-like 2 64404 5 5 4 0 0 3 1 1 0 0 1.9e-06 0.014
3 MLL3 myeloid/lymphoid or mixed-lineage leukemia 3 533196 8 7 8 2 0 1 1 0 4 2 2.3e-06 0.014
4 POU4F1 POU class 4 homeobox 1 27144 3 3 2 0 0 0 1 0 2 0 3.1e-06 0.014
5 OR5H6 olfactory receptor, family 5, subfamily H, member 6 35352 3 3 3 0 0 0 2 0 1 0 0.000023 0.074
6 AQP2 aquaporin 2 (collecting duct) 29376 3 3 3 0 2 0 1 0 0 0 0.000024 0.074
7 FCRL1 Fc receptor-like 1 48024 3 3 3 0 0 2 0 1 0 0 0.000038 0.098
8 TMEM51 transmembrane protein 51 27720 3 3 3 0 0 2 1 0 0 0 0.000072 0.15
9 COL11A2 collagen, type XI, alpha 2 182880 4 4 4 0 0 0 2 1 1 0 8e-05 0.15
10 DNAJB1 DnaJ (Hsp40) homolog, subfamily B, member 1 37260 4 3 4 0 0 2 1 0 1 0 0.000084 0.15
11 CDK11B 53604 3 3 3 1 0 1 1 0 1 0 0.000092 0.15
12 NFYB nuclear transcription factor Y, beta 23472 2 2 1 0 0 0 0 0 2 0 0.00011 0.16
13 SIGLEC10 sialic acid binding Ig-like lectin 10 76968 3 3 3 0 0 0 3 0 0 0 0.00012 0.17
14 MAPK1 mitogen-activated protein kinase 1 35712 3 3 1 0 0 3 0 0 0 0 0.00017 0.21
15 C15orf56 chromosome 15 open reading frame 56 5292 1 1 1 0 0 0 0 0 1 0 0.00017 0.21
16 ZIC3 Zic family member 3 heterotaxy 1 (odd-paired homolog, Drosophila) 37008 2 2 2 0 0 0 1 0 1 0 0.00027 0.3
17 SUMO1 SMT3 suppressor of mif two 3 homolog 1 (S. cerevisiae) 11736 2 2 2 0 0 0 1 1 0 0 0.00029 0.3
18 DALRD3 DALR anticodon binding domain containing 3 52776 3 2 3 1 0 0 2 1 0 0 0.0003 0.3
19 MYH9 myosin, heavy chain 9, non-muscle 217548 5 4 5 1 0 1 2 0 2 0 0.00033 0.3
20 TIE1 tyrosine kinase with immunoglobulin-like and EGF-like domains 1 118152 4 3 4 0 0 1 2 0 1 0 0.00034 0.3
21 HSD17B4 hydroxysteroid (17-beta) dehydrogenase 4 83052 3 3 3 2 0 2 0 0 1 0 0.00035 0.3
22 PTPN13 protein tyrosine phosphatase, non-receptor type 13 (APO-1/CD95 (Fas)-associated phosphatase) 267084 5 5 5 1 0 1 3 1 0 0 0.00039 0.32
23 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 44928 2 2 2 0 0 0 0 0 2 0 0.00043 0.33
24 B2M beta-2-microglobulin 13392 2 2 2 0 0 1 0 0 1 0 0.00044 0.33
25 SPANXN5 SPANX family, member N5 8172 1 1 1 0 0 0 0 0 1 0 0.00045 0.33
26 MTA2 metastasis associated 1 family, member 2 74844 2 2 2 0 1 0 0 0 1 0 0.00049 0.34
27 B3GNT8 UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 8 43128 2 2 2 0 0 1 0 0 1 0 0.00051 0.34
28 PRRG1 proline rich Gla (G-carboxyglutamic acid) 1 24084 2 2 2 0 0 1 0 0 1 0 0.00056 0.35
29 ARHGAP6 Rho GTPase activating protein 6 89496 3 3 3 1 0 2 1 0 0 0 0.00056 0.35
30 MUC17 mucin 17, cell surface associated 487224 6 6 6 2 0 1 4 0 1 0 0.00059 0.35
31 F2RL3 coagulation factor II (thrombin) receptor-like 3 38844 2 2 2 0 0 1 1 0 0 0 0.0006 0.35
32 PAX7 paired box 7 57420 2 2 2 0 0 1 0 0 1 0 0.00062 0.35
33 FAM49A family with sequence similarity 49, member A 36432 2 2 2 0 0 1 1 0 0 0 0.00066 0.36
34 DHRS12 dehydrogenase/reductase (SDR family) member 12 30276 2 2 2 0 0 0 0 0 2 0 0.00073 0.37
35 ARIH2 ariadne homolog 2 (Drosophila) 55368 3 2 3 0 0 0 2 0 1 0 0.00076 0.37

Note:

N - number of sequenced bases in this gene across the individual set.

n - number of (nonsilent) mutations in this gene across the individual set.

npat - number of patients (individuals) with at least one nonsilent mutation.

nsite - number of unique sites having a non-silent mutation.

nsil - number of silent mutations in this gene across the individual set.

n1 - number of nonsilent mutations of type: (A/T)p*A->T .

n2 - number of nonsilent mutations of type: (A/T)p*N->nonflip .

n3 - number of nonsilent mutations of type: (C/G)p*N->mut .

n4 - number of nonsilent mutations of type: (A/T)p*C->G .

n5 - number of nonsilent mutations of type: indel+null .

null - mutation category that includes nonsense, frameshift, splice-site mutations

p_classic = p-value for the observed amount of nonsilent mutations being elevated in this gene

p_ns_s = p-value for the observed nonsilent/silent ratio being elevated in this gene

p = p-value (overall)

q = q-value, False Discovery Rate (Benjamini-Hochberg procedure)

COSMIC analyses

In this analysis, COSMIC is used as a filter to increase power by restricting the territory of each gene. Cosmic version: v48.

Table 4.  Get Full Table Significantly mutated genes (COSMIC territory only). To access the database please go to: COSMIC. Number of significant genes found: 0. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 A4GNT alpha-1,4-N-acetylglucosaminyltransferase 1 0 0 0 0 1 1
2 AACS acetoacetyl-CoA synthetase 0 0 0 0 0 1 1
3 ABCA9 ATP-binding cassette, sub-family A (ABC1), member 9 0 0 0 0 0 1 1
4 ABCC10 ATP-binding cassette, sub-family C (CFTR/MRP), member 10 0 0 0 0 0 1 1
5 ABCF2 ATP-binding cassette, sub-family F (GCN20), member 2 0 0 0 0 0 1 1
6 ABHD2 abhydrolase domain containing 2 0 0 0 0 0 1 1
7 ABHD4 abhydrolase domain containing 4 0 0 0 0 0 1 1
8 ACADS acyl-Coenzyme A dehydrogenase, C-2 to C-3 short chain 0 0 0 0 0 1 1
9 ACOT11 acyl-CoA thioesterase 11 0 0 0 0 0 1 1
10 ACRBP acrosin binding protein 0 0 0 0 0 1 1

Note:

n - number of (nonsilent) mutations in this gene across the individual set.

cos = number of unique mutated sites in this gene in COSMIC

n_cos = overlap between n and cos.

N_cos = number of individuals times cos.

cos_ev = total evidence: number of reports in COSMIC for mutations seen in this gene.

p = p-value for seeing the observed amount of overlap in this gene)

q = q-value, False Discovery Rate (Benjamini-Hochberg procedure)

Clustered Mutations

Table 5.  Get Full Table Genes with Clustered Mutations

num gene desc n mindist npairs3 npairs12
975 FAT2 FAT tumor suppressor homolog 2 (Drosophila) 4 2465 0 0
2 A2M alpha-2-macroglobulin 2 Inf 0 0
7 AATF apoptosis antagonizing transcription factor 2 Inf 0 0
9 ABCA10 ATP-binding cassette, sub-family A (ABC1), member 10 2 Inf 0 0
10 ABCA12 ATP-binding cassette, sub-family A (ABC1), member 12 4 Inf 0 0
15 ABCA8 ATP-binding cassette, sub-family A (ABC1), member 8 2 Inf 0 0
16 ABCC3 ATP-binding cassette, sub-family C (CFTR/MRP), member 3 2 Inf 0 0
19 ABCD4 ATP-binding cassette, sub-family D (ALD), member 4 2 Inf 0 0
24 ABR active BCR-related gene 2 Inf 0 0
25 ACACB acetyl-Coenzyme A carboxylase beta 2 Inf 0 0

Note:

n - number of mutations in this gene in the individual set.

mindist - distance (in aa) between closest pair of mutations in this gene

npairs3 - how many pairs of mutations are within 3 aa of each other.

npairs12 - how many pairs of mutations are within 12 aa of each other.

Geneset Analyses

Table 6.  Get Full Table A Ranked List of Significantly Mutated Genesets. (Source: MSigDB GSEA Cannonical Pathway Set).Number of significant genesets found: 67. Number of genesets displayed: 10

rank geneset description genes N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 n6 p q
1 HSA04510_FOCAL_ADHESION Genes involved in focal adhesion ACTB, ACTG1, ACTN1, ACTN2, ACTN3, ACTN4, AKT1, AKT2, AKT3, ARHGAP5, BAD, BCAR1, BCL2, BIRC2, BIRC3, BIRC4, BRAF, CAPN2, CAV1, CAV2, CAV3, CCND1, CCND2, CCND3, CDC42, CHAD, COL11A1, COL11A2, COL1A1, COL1A2, COL2A1, COL3A1, COL4A1, COL4A2, COL4A4, COL4A6, COL5A1, COL5A2, COL5A3, COL6A1, COL6A2, COL6A3, COL6A6, COMP, CRK, CRKL, CTNNB1, DIAPH1, DOCK1, EGF, EGFR, ELK1, ERBB2, FARP2, FIGF, FLNA, FLNB, FLNC, FLT1, FN1, FYN, GRB2, GRLF1, GSK3B, HGF, HRAS, IBSP, IGF1, IGF1R, ILK, ITGA1, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAV, ITGB1, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, ITGB8, JUN, KDR, LAMA1, LAMA2, LAMA3, LAMA4, LAMA5, LAMB1, LAMB2, LAMB3, LAMB4, LAMC1, LAMC2, LAMC3, LOC653852, MAP2K1, MAPK1, MAPK10, MAPK3, MAPK8, MAPK9, MET, MLCK, MRCL3, MRLC2, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLK, MYLK2, MYLPF, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PARVA, PARVB, PARVG, PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA, PDGFRB, PDPK1, PGF, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIP5K1C, PPP1CA, PPP1CB, PPP1CC, PPP1R12A, PRKCA, PRKCB1, PRKCG, PTEN, PTK2, PXN, RAC1, RAC2, RAC3, RAF1, RAP1A, RAP1B, RAPGEF1, RELN, RHOA, ROCK1, ROCK2, SHC1, SHC2, SHC3, SHC4, SOS1, SOS2, SPP1, SRC, THBS1, THBS2, THBS3, THBS4, TLN1, TLN2, TNC, TNN, TNR, TNXB, VASP, VAV1, VAV2, VAV3, VCL, VEGFA, VEGFB, VEGFC, VTN, VWF, ZYX 192 ACTN1(1), ACTN3(1), ACTN4(1), AKT3(1), BRAF(1), COL11A2(4), COL1A2(2), COL3A1(1), COL4A1(1), COL5A1(1), COL5A3(2), COL6A3(2), COMP(1), EGFR(1), ERBB2(1), FLNA(2), FLNC(1), FN1(2), GRLF1(1), ITGA4(1), ITGA7(2), ITGA8(2), ITGAV(1), LAMA1(2), LAMA2(1), LAMA4(1), LAMA5(1), LAMB1(1), LAMB2(1), LAMB3(1), MAPK1(3), PAK2(1), PAK3(1), PDGFC(1), PIK3CA(9), PIK3CD(1), PIK3CG(1), PIK3R1(1), PPP1CB(1), PPP1R12A(3), PRKCA(1), PTEN(2), PTK2(1), RELN(2), RHOA(1), ROCK1(3), ROCK2(2), SOS1(1), SOS2(1), TNC(2), TNXB(2), VWF(1) 20561688 82 30 74 18 7 27 32 3 13 0 4e-09 2.4e-06
2 HSA04810_REGULATION_OF_ACTIN_CYTOSKELETON Genes involved in regulation of actin cytoskeleton ABI2, ACTN1, ACTN2, ACTN3, ACTN4, APC, APC2, ARAF, ARHGEF1, ARHGEF12, ARHGEF4, ARHGEF6, ARHGEF7, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, ARPC5, ARPC5L, BAIAP2, BCAR1, BDKRB1, BDKRB2, BRAF, C3orf10, CD14, CDC42, CFL1, CFL2, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, CRK, CRKL, CSK, CYFIP1, CYFIP2, DIAPH1, DIAPH2, DIAPH3, DOCK1, EGF, EGFR, EZR, F2, F2R, FGD1, FGD3, FGF1, FGF10, FGF11, FGF12, FGF13, FGF14, FGF16, FGF17, FGF18, FGF19, FGF2, FGF20, FGF21, FGF22, FGF23, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, FGFR1, FGFR2, FGFR3, FGFR4, FN1, GIT1, GNA12, GNA13, GNG12, GRLF1, GSN, HRAS, INS, IQGAP1, IQGAP2, IQGAP3, ITGA1, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAD, ITGAE, ITGAL, ITGAM, ITGAV, ITGAX, ITGB1, ITGB2, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, ITGB8, KRAS, LIMK1, LIMK2, LOC200025, LOC645126, LOC653888, MAP2K1, MAP2K2, MAPK1, MAPK3, MLCK, MOS, MRAS, MRCL3, MRLC2, MSN, MYH10, MYH14, MYH9, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLK, MYLK2, MYLPF, NCKAP1, NCKAP1L, NRAS, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PDGFA, PDGFB, PDGFRA, PDGFRB, PFN1, PFN2, PFN3, PFN4, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIP4K2A, PIP4K2B, PIP4K2C, PIP5K1A, PIP5K1B, PIP5K1C, PIP5K3, PPP1CA, PPP1CB, PPP1CC, PPP1R12A, PPP1R12B, PTK2, PXN, RAC1, RAC2, RAC3, RAF1, RDX, RHOA, ROCK1, ROCK2, RRAS, RRAS2, SCIN, SLC9A1, SOS1, SOS2, SSH1, SSH2, SSH3, TIAM1, TIAM2, TMSB4X, TMSB4Y, TMSL3, VAV1, VAV2, VAV3, VCL, WAS, WASF1, WASF2, WASL 203 ACTN1(1), ACTN3(1), ACTN4(1), APC(3), ARHGEF6(1), ARPC5(1), BRAF(1), CYFIP1(1), DIAPH3(2), EGFR(1), EZR(1), F2R(1), FGF17(1), FGF2(1), FGF9(1), FN1(2), GNA13(1), GRLF1(1), ITGA4(1), ITGA7(2), ITGA8(2), ITGAE(1), ITGAM(2), ITGAV(1), KRAS(1), LIMK1(1), MAPK1(3), MYH10(2), MYH14(2), MYH9(5), NCKAP1(1), NCKAP1L(1), PAK2(1), PAK3(1), PIK3CA(9), PIK3CD(1), PIK3CG(1), PIK3R1(1), PIP5K1A(1), PPP1CB(1), PPP1R12A(3), PTK2(1), RHOA(1), ROCK1(3), ROCK2(2), SLC9A1(2), SOS1(1), SOS2(1), SSH2(1), SSH3(1), TIAM1(1), WASF2(1) 15386760 81 29 73 28 9 29 23 5 15 0 1.3e-07 4e-05
3 HSA04320_DORSO_VENTRAL_AXIS_FORMATION Genes involved in dorso-ventral axis formation BRAF, CPEB1, EGFR, ERBB2, ERBB4, ETS1, ETS2, ETV6, ETV7, FMN2, GRB2, KRAS, MAP2K1, MAPK1, MAPK3, NOTCH1, NOTCH2, NOTCH3, NOTCH4, PIWIL1, PIWIL2, PIWIL3, PIWIL4, RAF1, SOS1, SOS2, SPIRE1, SPIRE2 28 BRAF(1), EGFR(1), ERBB2(1), FMN2(1), KRAS(1), MAPK1(3), NOTCH1(6), NOTCH2(2), NOTCH4(1), PIWIL1(2), PIWIL3(1), PIWIL4(2), SOS1(1), SOS2(1) 2917044 24 17 22 3 2 8 8 1 5 0 0.000014 0.0024
4 ST_INTEGRIN_SIGNALING_PATHWAY Integrins are transmembrane receptors that mediate cell growth, survival, and migration by binding to ligands in the extracellular matrix. ABL1, ACK1, ACTN1, ACTR2, ACTR3, AKT1, AKT2, AKT3, ANGPTL2, ARHGEF6, ARHGEF7, BCAR1, BRAF, CAV1, CDC42, CDKN2A, CRK, CSE1L, DDEF1, DOCK1, EPHB2, FYN, GRAF, GRB2, GRB7, GRF2, GRLF1, ILK, ITGA1, ITGA10, ITGA11, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGB3BP, MAP2K4, MAP2K7, MAP3K11, MAPK1, MAPK10, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, MRAS, MYLK, MYLK2, P4HB, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PIK3CA, PIK3CB, PKLR, PLCG1, PLCG2, PTEN, PTK2, RAF1, RALA, RHO, ROCK1, ROCK2, SHC1, SOS1, SOS2, SRC, TERF2IP, TLN1, TLN2, VASP, WAS, ZYX 78 ABL1(1), ACTN1(1), AKT3(1), ARHGEF6(1), BRAF(1), EPHB2(1), GRLF1(1), ITGA4(1), ITGA7(2), ITGA8(2), MAPK1(3), PAK2(1), PAK3(1), PIK3CA(9), PLCG2(1), PTEN(2), PTK2(1), ROCK1(3), ROCK2(2), SOS1(1), SOS2(1) 6762672 37 21 29 9 6 12 10 1 8 0 0.000016 0.0024
5 HSA04670_LEUKOCYTE_TRANSENDOTHELIAL_MIGRATION Genes involved in Leukocyte transendothelial migration ACTN1, ACTN2, ACTN3, ACTN4, ARHGAP5, BCAR1, CD99, CDC42, CDH5, CLDN1, CLDN10, CLDN11, CLDN14, CLDN15, CLDN16, CLDN17, CLDN18, CLDN19, CLDN2, CLDN20, CLDN22, CLDN23, CLDN3, CLDN4, CLDN5, CLDN6, CLDN7, CLDN8, CLDN9, CTNNA1, CTNNA2, CTNNA3, CTNNB1, CTNND1, CXCL12, CXCR4, CYBA, CYBB, ESAM, EZR, F11R, GNAI1, GNAI2, GNAI3, GRLF1, ICAM1, ITGA4, ITGAL, ITGAM, ITGB1, ITGB2, ITK, JAM2, JAM3, MAPK11, MAPK12, MAPK13, MAPK14, MLLT4, MMP2, MMP9, MRCL3, MRLC2, MSN, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLPF, NCF1, NCF2, NCF4, NOX1, NOX3, OCLN, PECAM1, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PLCG1, PLCG2, PRKCA, PRKCB1, PRKCG, PTK2, PTK2B, PTPN11, PXN, RAC1, RAC2, RAP1A, RAP1B, RAPGEF3, RAPGEF4, RASSF5, RHOA, RHOH, ROCK1, ROCK2, SIPA1, THY1, TXK, VASP, VAV1, VAV2, VAV3, VCAM1, VCL 109 ACTN1(1), ACTN3(1), ACTN4(1), CLDN18(1), CTNNA1(1), CTNNA2(2), CTNNA3(2), EZR(1), GNAI2(1), GRLF1(1), ITGA4(1), ITGAM(2), NOX1(1), NOX3(1), PIK3CA(9), PIK3CD(1), PIK3CG(1), PIK3R1(1), PLCG2(1), PRKCA(1), PTK2(1), RHOA(1), ROCK1(3), ROCK2(2) 6935364 38 20 32 14 8 8 15 2 5 0 0.000044 0.0046
6 NOTCHPATHWAY Proteolysis and Signaling Pathway of Notch ADAM17, DLL1, FURIN, NOTCH1, PSEN1, RBPSUH 5 ADAM17(1), DLL1(1), NOTCH1(6), PSEN1(2) 537840 10 7 10 2 0 3 5 0 2 0 0.000044 0.0046
7 SIG_CHEMOTAXIS Genes related to chemotaxis ACTR2, ACTR3, AKT1, AKT2, AKT3, ANGPTL2, ARHGAP1, ARHGAP4, ARHGEF11, BTK, CDC42, CFL1, CFL2, GDI1, GDI2, INPPL1, ITPR1, ITPR2, ITPR3, LIMK1, MYLK, MYLK2, P101-PI3K, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PDK1, PIK3CA, PIK3CD, PIK3CG, PIK3R1, PITX2, PPP1R13B, PTEN, RACGAP1, RHO, ROCK1, ROCK2, RPS4X, SAG, WASF1, WASL 44 AKT3(1), ARHGAP4(2), ARHGEF11(1), BTK(1), GDI1(1), ITPR2(1), LIMK1(1), PAK2(1), PAK3(1), PDK1(1), PIK3CA(9), PIK3CD(1), PIK3CG(1), PIK3R1(1), PTEN(2), ROCK1(3), ROCK2(2), RPS4X(1), SAG(1) 3887316 32 17 26 2 6 4 16 1 5 0 0.000071 0.0052
8 SA_PTEN_PATHWAY PTEN is a tumor suppressor that dephosphorylates the lipid messenger phosphatidylinositol triphosphate. AKT1, AKT2, AKT3, BPNT1, GRB2, ILK, MAPK1, MAPK3, PDK1, PIK3CA, PIK3CD, PIP3-E, PTEN, PTK2B, RBL2, SHC1, SOS1 16 AKT3(1), MAPK1(3), PDK1(1), PIK3CA(9), PIK3CD(1), PTEN(2), RBL2(1), SOS1(1) 1114344 19 11 11 0 5 5 7 0 2 0 0.000072 0.0052
9 MTORPATHWAY Mammalian target of rapamycin (mTOR) senses mitogenic factors and nutrients, including ATP, and induces cell proliferation. AKT1, EIF3S10, EIF4A1, EIF4A2, EIF4B, EIF4E, EIF4EBP1, EIF4G1, EIF4G2, EIF4G3, FKBP1A, FRAP1, MKNK1, PDK2, PDPK1, PIK3CA, PIK3R1, PPP2CA, PTEN, RPS6, RPS6KB1, TSC1, TSC2 21 EIF4A1(1), EIF4B(1), EIF4G1(3), MKNK1(1), PIK3CA(9), PIK3R1(1), PTEN(2), TSC1(1), TSC2(1) 1515564 20 12 14 3 6 3 9 0 2 0 0.000077 0.0052
10 ARENRF2PATHWAY Nrf1 and nrf2 are transcription factors that bind to antioxidant response elements (AREs), promoters of genes involved in oxidative damage control. CREB1, FOS, FXYD2, JUN, KEAP1, MAFF, MAFG, MAFK, MAPK1, MAPK14, MAPK8, NFE2L2, PRKCA, PRKCB1 12 MAPK1(3), NFE2L2(5), PRKCA(1) 482076 9 8 6 0 0 7 1 1 0 0 0.00012 0.0074

Table 7.  Get Full Table A Ranked List of Significantly Mutated Genesets (Excluding Significantly Mutated Genes). Number of significant genesets found: 19. Number of genesets displayed: 10

rank geneset description genes N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 n6 p q
1 HSA04810_REGULATION_OF_ACTIN_CYTOSKELETON Genes involved in regulation of actin cytoskeleton ABI2, ACTN1, ACTN2, ACTN3, ACTN4, APC, APC2, ARAF, ARHGEF1, ARHGEF12, ARHGEF4, ARHGEF6, ARHGEF7, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, ARPC5, ARPC5L, BAIAP2, BCAR1, BDKRB1, BDKRB2, BRAF, C3orf10, CD14, CDC42, CFL1, CFL2, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, CRK, CRKL, CSK, CYFIP1, CYFIP2, DIAPH1, DIAPH2, DIAPH3, DOCK1, EGF, EGFR, EZR, F2, F2R, FGD1, FGD3, FGF1, FGF10, FGF11, FGF12, FGF13, FGF14, FGF16, FGF17, FGF18, FGF19, FGF2, FGF20, FGF21, FGF22, FGF23, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, FGFR1, FGFR2, FGFR3, FGFR4, FN1, GIT1, GNA12, GNA13, GNG12, GRLF1, GSN, HRAS, INS, IQGAP1, IQGAP2, IQGAP3, ITGA1, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAD, ITGAE, ITGAL, ITGAM, ITGAV, ITGAX, ITGB1, ITGB2, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, ITGB8, KRAS, LIMK1, LIMK2, LOC200025, LOC645126, LOC653888, MAP2K1, MAP2K2, MAPK1, MAPK3, MLCK, MOS, MRAS, MRCL3, MRLC2, MSN, MYH10, MYH14, MYH9, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLK, MYLK2, MYLPF, NCKAP1, NCKAP1L, NRAS, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PDGFA, PDGFB, PDGFRA, PDGFRB, PFN1, PFN2, PFN3, PFN4, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIP4K2A, PIP4K2B, PIP4K2C, PIP5K1A, PIP5K1B, PIP5K1C, PIP5K3, PPP1CA, PPP1CB, PPP1CC, PPP1R12A, PPP1R12B, PTK2, PXN, RAC1, RAC2, RAC3, RAF1, RDX, RHOA, ROCK1, ROCK2, RRAS, RRAS2, SCIN, SLC9A1, SOS1, SOS2, SSH1, SSH2, SSH3, TIAM1, TIAM2, TMSB4X, TMSB4Y, TMSL3, VAV1, VAV2, VAV3, VCL, WAS, WASF1, WASF2, WASL 202 ACTN1(1), ACTN3(1), ACTN4(1), APC(3), ARHGEF6(1), ARPC5(1), BRAF(1), CYFIP1(1), DIAPH3(2), EGFR(1), EZR(1), F2R(1), FGF17(1), FGF2(1), FGF9(1), FN1(2), GNA13(1), GRLF1(1), ITGA4(1), ITGA7(2), ITGA8(2), ITGAE(1), ITGAM(2), ITGAV(1), KRAS(1), LIMK1(1), MAPK1(3), MYH10(2), MYH14(2), MYH9(5), NCKAP1(1), NCKAP1L(1), PAK2(1), PAK3(1), PIK3CD(1), PIK3CG(1), PIK3R1(1), PIP5K1A(1), PPP1CB(1), PPP1R12A(3), PTK2(1), RHOA(1), ROCK1(3), ROCK2(2), SLC9A1(2), SOS1(1), SOS2(1), SSH2(1), SSH3(1), TIAM1(1), WASF2(1) 15268428 72 27 70 28 4 29 19 5 15 0 1.7e-06 0.00052
2 HSA04510_FOCAL_ADHESION Genes involved in focal adhesion ACTB, ACTG1, ACTN1, ACTN2, ACTN3, ACTN4, AKT1, AKT2, AKT3, ARHGAP5, BAD, BCAR1, BCL2, BIRC2, BIRC3, BIRC4, BRAF, CAPN2, CAV1, CAV2, CAV3, CCND1, CCND2, CCND3, CDC42, CHAD, COL11A1, COL11A2, COL1A1, COL1A2, COL2A1, COL3A1, COL4A1, COL4A2, COL4A4, COL4A6, COL5A1, COL5A2, COL5A3, COL6A1, COL6A2, COL6A3, COL6A6, COMP, CRK, CRKL, CTNNB1, DIAPH1, DOCK1, EGF, EGFR, ELK1, ERBB2, FARP2, FIGF, FLNA, FLNB, FLNC, FLT1, FN1, FYN, GRB2, GRLF1, GSK3B, HGF, HRAS, IBSP, IGF1, IGF1R, ILK, ITGA1, ITGA10, ITGA11, ITGA2, ITGA2B, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGAV, ITGB1, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7, ITGB8, JUN, KDR, LAMA1, LAMA2, LAMA3, LAMA4, LAMA5, LAMB1, LAMB2, LAMB3, LAMB4, LAMC1, LAMC2, LAMC3, LOC653852, MAP2K1, MAPK1, MAPK10, MAPK3, MAPK8, MAPK9, MET, MLCK, MRCL3, MRLC2, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLK, MYLK2, MYLPF, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PARVA, PARVB, PARVG, PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA, PDGFRB, PDPK1, PGF, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R5, PIP5K1C, PPP1CA, PPP1CB, PPP1CC, PPP1R12A, PRKCA, PRKCB1, PRKCG, PTEN, PTK2, PXN, RAC1, RAC2, RAC3, RAF1, RAP1A, RAP1B, RAPGEF1, RELN, RHOA, ROCK1, ROCK2, SHC1, SHC2, SHC3, SHC4, SOS1, SOS2, SPP1, SRC, THBS1, THBS2, THBS3, THBS4, TLN1, TLN2, TNC, TNN, TNR, TNXB, VASP, VAV1, VAV2, VAV3, VCL, VEGFA, VEGFB, VEGFC, VTN, VWF, ZYX 191 ACTN1(1), ACTN3(1), ACTN4(1), AKT3(1), BRAF(1), COL11A2(4), COL1A2(2), COL3A1(1), COL4A1(1), COL5A1(1), COL5A3(2), COL6A3(2), COMP(1), EGFR(1), ERBB2(1), FLNA(2), FLNC(1), FN1(2), GRLF1(1), ITGA4(1), ITGA7(2), ITGA8(2), ITGAV(1), LAMA1(2), LAMA2(1), LAMA4(1), LAMA5(1), LAMB1(1), LAMB2(1), LAMB3(1), MAPK1(3), PAK2(1), PAK3(1), PDGFC(1), PIK3CD(1), PIK3CG(1), PIK3R1(1), PPP1CB(1), PPP1R12A(3), PRKCA(1), PTEN(2), PTK2(1), RELN(2), RHOA(1), ROCK1(3), ROCK2(2), SOS1(1), SOS2(1), TNC(2), TNXB(2), VWF(1) 20443356 73 27 71 18 2 27 28 3 13 0 1.7e-06 0.00052
3 HSA04320_DORSO_VENTRAL_AXIS_FORMATION Genes involved in dorso-ventral axis formation BRAF, CPEB1, EGFR, ERBB2, ERBB4, ETS1, ETS2, ETV6, ETV7, FMN2, GRB2, KRAS, MAP2K1, MAPK1, MAPK3, NOTCH1, NOTCH2, NOTCH3, NOTCH4, PIWIL1, PIWIL2, PIWIL3, PIWIL4, RAF1, SOS1, SOS2, SPIRE1, SPIRE2 28 BRAF(1), EGFR(1), ERBB2(1), FMN2(1), KRAS(1), MAPK1(3), NOTCH1(6), NOTCH2(2), NOTCH4(1), PIWIL1(2), PIWIL3(1), PIWIL4(2), SOS1(1), SOS2(1) 2917044 24 17 22 3 2 8 8 1 5 0 0.000014 0.0028
4 NOTCHPATHWAY Proteolysis and Signaling Pathway of Notch ADAM17, DLL1, FURIN, NOTCH1, PSEN1, RBPSUH 5 ADAM17(1), DLL1(1), NOTCH1(6), PSEN1(2) 537840 10 7 10 2 0 3 5 0 2 0 0.000044 0.0068
5 HSA05130_PATHOGENIC_ESCHERICHIA_COLI_INFECTION_EHEC Genes involved in pathogenic Escherichia coli infection - EHEC ABL1, ACTB, ACTG1, ARHGEF2, ARPC5, ARPC5L, CD14, CDC42, CDH1, CLDN1, CTNNB1, CTTN, EZR, FYN, HCLS1, ITGB1, KRT18, LOC643224, LOC654264, LY96, NCK1, NCK2, NCL, OCLN, PRKCA, RHOA, ROCK1, ROCK2, TLR4, TLR5, TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA8, TUBAL3, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB2C, TUBB3, TUBB4, TUBB4Q, TUBB6, TUBB8, WAS, WASL, YWHAQ, YWHAZ 51 ABL1(1), ARHGEF2(2), ARPC5(1), CTTN(1), EZR(1), LY96(1), PRKCA(1), RHOA(1), ROCK1(3), ROCK2(2), TUBA1C(1), TUBA3C(1), TUBA8(1), TUBB4(1), YWHAZ(1) 2897604 19 13 19 8 2 3 8 1 5 0 0.00015 0.015
6 HSA05131_PATHOGENIC_ESCHERICHIA_COLI_INFECTION_EPEC Genes involved in pathogenic Escherichia coli infection - EPEC ABL1, ACTB, ACTG1, ARHGEF2, ARPC5, ARPC5L, CD14, CDC42, CDH1, CLDN1, CTNNB1, CTTN, EZR, FYN, HCLS1, ITGB1, KRT18, LOC643224, LOC654264, LY96, NCK1, NCK2, NCL, OCLN, PRKCA, RHOA, ROCK1, ROCK2, TLR4, TLR5, TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA8, TUBAL3, TUBB, TUBB1, TUBB2A, TUBB2B, TUBB2C, TUBB3, TUBB4, TUBB4Q, TUBB6, TUBB8, WAS, WASL, YWHAQ, YWHAZ 51 ABL1(1), ARHGEF2(2), ARPC5(1), CTTN(1), EZR(1), LY96(1), PRKCA(1), RHOA(1), ROCK1(3), ROCK2(2), TUBA1C(1), TUBA3C(1), TUBA8(1), TUBB4(1), YWHAZ(1) 2897604 19 13 19 8 2 3 8 1 5 0 0.00015 0.015
7 HSA04530_TIGHT_JUNCTION Genes involved in tight junction ACTB, ACTG1, ACTN1, ACTN2, ACTN3, ACTN4, AKT1, AKT2, AKT3, AMOTL1, ASH1L, CASK, CDC42, CDK4, CGN, CLDN1, CLDN10, CLDN11, CLDN14, CLDN15, CLDN16, CLDN17, CLDN18, CLDN19, CLDN2, CLDN20, CLDN22, CLDN23, CLDN3, CLDN4, CLDN5, CLDN6, CLDN7, CLDN8, CLDN9, CRB3, CSDA, CSNK2A1, CSNK2A2, CSNK2B, CTNNA1, CTNNA2, CTNNA3, CTNNB1, CTTN, EPB41, EPB41L1, EPB41L2, EPB41L3, EXOC3, EXOC4, F11R, GNAI1, GNAI2, GNAI3, HCLS1, HRAS, IGSF5, INADL, JAM2, JAM3, KRAS, LLGL1, LLGL2, MAGI1, MAGI2, MAGI3, MLLT4, MPDZ, MPP5, MRAS, MRCL3, MRLC2, MYH1, MYH10, MYH11, MYH13, MYH14, MYH15, MYH2, MYH3, MYH4, MYH6, MYH7, MYH7B, MYH8, MYH9, MYL2, MYL5, MYL7, MYL8P, MYL9, MYLC2PL, MYLPF, NRAS, OCLN, PARD3, PARD6A, PARD6B, PARD6G, PPM1J, PPP2CA, PPP2CB, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R2B, PPP2R2C, PPP2R3A, PPP2R3B, PPP2R4, PRKCA, PRKCB1, PRKCD, PRKCE, PRKCG, PRKCH, PRKCI, PRKCQ, PRKCZ, PTEN, RAB13, RAB3B, RHOA, RRAS, RRAS2, SPTAN1, SRC, SYMPK, TJAP1, TJP1, TJP2, TJP3, VAPA, YES1, ZAK 130 ACTN1(1), ACTN3(1), ACTN4(1), AKT3(1), AMOTL1(1), ASH1L(2), CGN(1), CLDN18(1), CTNNA1(1), CTNNA2(2), CTNNA3(2), CTTN(1), EPB41(1), GNAI2(1), KRAS(1), LLGL2(1), MAGI1(1), MAGI2(1), MYH1(3), MYH10(2), MYH11(1), MYH13(1), MYH14(2), MYH15(2), MYH2(1), MYH3(1), MYH6(3), MYH7(1), MYH7B(1), MYH8(3), MYH9(5), PARD3(1), PPM1J(1), PPP2R1A(1), PPP2R3A(1), PRKCA(1), PTEN(2), RHOA(1), SPTAN1(2) 10681812 57 23 57 18 4 17 21 5 10 0 0.0004 0.032
8 PS1PATHWAY Presenilin is required for gamma-secretase activity to activate Notch signaling; presenilin also inhibits beta-catenin in the Wnt/Frizzled pathway. ADAM17, APC, AXIN1, BTRC, CTNNB1, DLL1, DVL1, FZD1, GSK3B, NOTCH1, PSEN1, RBPSUH, TCF1, WNT1 12 ADAM17(1), APC(3), DLL1(1), NOTCH1(6), PSEN1(2) 1174716 13 9 13 2 0 4 6 1 2 0 0.00042 0.032
9 ST_TYPE_I_INTERFERON_PATHWAY Type I interferon is an antiviral cytokine that induces a JAK-STAT type pathway leading to ISGF3 activation and a cellular antiviral response. IFNAR1, IFNB1, ISGF3G, JAK1, PTPRU, REG1A, STAT1, STAT2, TYK2 8 IFNAR1(1), REG1A(1), STAT1(2), TYK2(3) 684288 7 7 7 1 0 3 3 1 0 0 0.00052 0.035
10 ST_INTEGRIN_SIGNALING_PATHWAY Integrins are transmembrane receptors that mediate cell growth, survival, and migration by binding to ligands in the extracellular matrix. ABL1, ACK1, ACTN1, ACTR2, ACTR3, AKT1, AKT2, AKT3, ANGPTL2, ARHGEF6, ARHGEF7, BCAR1, BRAF, CAV1, CDC42, CDKN2A, CRK, CSE1L, DDEF1, DOCK1, EPHB2, FYN, GRAF, GRB2, GRB7, GRF2, GRLF1, ILK, ITGA1, ITGA10, ITGA11, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGB3BP, MAP2K4, MAP2K7, MAP3K11, MAPK1, MAPK10, MAPK8, MAPK8IP1, MAPK8IP2, MAPK8IP3, MAPK9, MRAS, MYLK, MYLK2, P4HB, PAK1, PAK2, PAK3, PAK4, PAK6, PAK7, PIK3CA, PIK3CB, PKLR, PLCG1, PLCG2, PTEN, PTK2, RAF1, RALA, RHO, ROCK1, ROCK2, SHC1, SOS1, SOS2, SRC, TERF2IP, TLN1, TLN2, VASP, WAS, ZYX 77 ABL1(1), ACTN1(1), AKT3(1), ARHGEF6(1), BRAF(1), EPHB2(1), GRLF1(1), ITGA4(1), ITGA7(2), ITGA8(2), MAPK1(3), PAK2(1), PAK3(1), PLCG2(1), PTEN(2), PTK2(1), ROCK1(3), ROCK2(2), SOS1(1), SOS2(1) 6644340 28 18 26 9 1 12 6 1 8 0 0.00057 0.035
Methods & Data
Methods

In brief, we tabulate the number of mutations and the number of covered bases for each gene. The counts are broken down by mutation context category: four context categories that are discovered by MutSig, and one for indel and 'null' mutations, which include indels, nonsense mutations, splice-site mutations, and non-stop (read-through) mutations. For each gene, we calculate the probability of seeing the observed constellation of mutations, i.e. the product P1 x P2 x ... x Pm, or a more extreme one, given the background mutation rates calculated across the dataset.[1]

References
[1] TCGA, Integrated genomic analyses of ovarian carcinoma, Nature 474:609 Ð 615 (2011)
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