Kidney Renal Clear Cell Carcinoma: Mutation Analysis (MutSig v2.0)
Maintained by Dan DiCara (Broad Institute)
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 v2.0 was used to generate the results found in this report.

  • Working with individual set: KIRC

  • Number of patients in set: 293

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

  • MAF used for this analysis:KIRC.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 42

  • Mutations seen in COSMIC: 345

  • Significantly mutated genes in COSMIC territory: 85

  • Genes with clustered mutations (≤ 3 aa apart): 198

  • Significantly mutated genesets: 5

  • Significantly mutated genesets: (excluding sig. mutated genes):0

Mutation Preprocessing

  • Read 293 MAFs of type "Broad"

  • Read 66 MAFs of type "Baylor"

  • Total number of mutations in input MAFs: 99658

  • After removing 232 mutations outside chr1-24: 99426

  • After removing 70518 noncoding mutations: 28908

  • After collapsing adjacent/redundant mutations: 26038

Mutation Filtering

  • Number of mutations before filtering: 26038

  • After removing 802 mutations outside gene set: 25236

  • After removing 111 mutations outside category set: 25125

  • After removing 1 "impossible" mutations in

  • gene-patient-category bins of zero coverage: 25124

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 440
Frame_Shift_Ins 114
In_Frame_Del 129
In_Frame_Ins 43
Missense_Mutation 16106
Nonsense_Mutation 1080
Nonstop_Mutation 21
Silent 6625
Splice_Site 525
Translation_Start_Site 42
Total 25125
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 exp_ns_s_ratio
*CpG->T 1767 484078369 3.7e-06 3.7 1.7 2.1
*ApG->G 1226 1342141277 9.1e-07 0.91 0.43 2.1
*Np(A/C/T)->transit 5303 6921093572 7.7e-07 0.77 0.36 2
transver 7785 8747313218 8.9e-07 0.89 0.42 5
indel+null 2411 8747313218 2.8e-07 0.28 0.13 NaN
double_null 8 8747313218 9.1e-10 0.00091 0.00043 NaN
Total 18500 8747313218 2.1e-06 2.1 1 3.5
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.  Patients counts and rates file used to generate this plot: KIRC.patients.counts_and_rates.txt

CoMut Plot

Figure 3.  Get High-res Image The matrix in the center of the figure represents individual mutations in patient samples, color-coded by type of mutation, for the significantly mutated genes. The rate of synonymous and non-synonymous mutations is displayed at the top of the matrix. The barplot on the left of the matrix shows the number of mutations in each gene. The percentages represent the fraction of tumors with at least one mutation in the specified gene. The barplot to the right of the matrix displays the q-values for the most significantly mutated genes. The purple boxplots below the matrix (only displayed if required columns are present in the provided MAF) represent the distributions of allelic fractions observed in each sample. The plot at the bottom represents the base substitution distribution of individual samples, using the same categories that were used to calculate significance.

Significantly Mutated Genes

Column Descriptions:

  • 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: *CpG->T

  • n2 = number of nonsilent mutations of type: *ApG->G

  • n3 = number of nonsilent mutations of type: *Np(A/C/T)->transit

  • n4 = number of nonsilent mutations of type: transver

  • n5 = number of nonsilent mutations of type: indel+null

  • n6 = number of nonsilent mutations of type: double_null

  • 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_ks = p-value for clustering of mutations (Kolmogorov-Smirnoff test)

  • p_cons = p-value for enrichment of mutations at evolutionarily most-conserved sites in gene

  • p_joint = p-value for clustering + conservation

  • p = p-value (overall)

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

Table 3.  Get Full Table A Ranked List of Significantly Mutated Genes. Number of significant genes found: 42. Number of genes displayed: 35. Click on a gene name to display its stick figure depicting the distribution of mutations and mutation types across the chosen gene (this feature may not be available for all significant genes).

rank gene description N n npat nsite nsil n1 n2 n3 n4 n5 n6 p_classic p_ns_s p_ks p_cons p_joint p q
1 SETD2 SET domain containing 2 1866089 32 32 32 1 2 2 2 7 18 1 2.78e-15 0.0038 0.009 0.057 0.0057 6.66e-16 3.62e-12
2 VHL von Hippel-Lindau tumor suppressor 123072 150 146 96 2 2 14 15 33 86 0 <1.00e-15 2.3e-11 2e-07 2e-07 0 <1.00e-15 <3.62e-12
3 SV2C synaptic vesicle glycoprotein 2C 653960 3 3 3 0 0 1 1 0 1 0 0.0731 0.3 0.14 0.0017 0 <1.00e-15 <3.62e-12
4 TOR1A torsin family 1, member A (torsin A) 280456 3 3 1 0 0 0 3 0 0 0 0.0160 0.27 4e-06 0.001 0 <1.00e-15 <3.62e-12
5 TPST1 tyrosylprotein sulfotransferase 1 330797 2 2 2 0 0 0 0 1 1 0 0.0662 0.74 0.08 0.00084 0 <1.00e-15 <3.62e-12
6 PBRM1 polybromo 1 1470408 100 98 98 2 0 1 6 15 78 0 <1.00e-15 0.000013 0.036 0.12 0.032 <1.22e-15 <3.69e-12
7 BAP1 BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) 589189 28 27 25 1 0 2 6 5 14 1 3.44e-15 0.0024 0.031 0.4 0.047 6.00e-15 1.55e-11
8 KDM5C lysine (K)-specific demethylase 5C 1253863 18 18 18 1 0 0 2 5 11 0 1.41e-11 0.1 0.0047 0.21 0.0066 2.89e-12 6.54e-09
9 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 365609 16 15 16 2 0 1 5 3 7 0 2.64e-12 0.11 0.11 0.91 0.18 1.43e-11 2.88e-08
10 STAG3L2 stromal antigen 3-like 2 83876 6 6 2 0 0 0 0 0 6 0 1.29e-09 1 0.0012 0.16 0.0016 5.88e-11 1.06e-07
11 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 963086 14 14 13 1 0 2 6 5 1 0 2.17e-08 0.06 0.0014 0.21 0.0014 7.84e-10 1.29e-06
12 MTOR mechanistic target of rapamycin (serine/threonine kinase) 2294678 26 24 22 2 1 2 4 19 0 0 2.53e-08 0.043 0.0052 0.48 0.0092 5.40e-09 8.16e-06
13 EBPL emopamil binding protein-like 139558 7 6 3 0 1 0 0 6 0 0 2.98e-07 0.2 0.00032 1 0.00097 6.64e-09 9.25e-06
14 FAM174B family with sequence similarity 174, member B 72325 3 3 1 0 0 0 0 0 3 0 0.000107 1 4.8e-06 0.91 5.6e-06 1.33e-08 1.72e-05
15 NUDT11 nudix (nucleoside diphosphate linked moiety X)-type motif 11 127356 3 3 1 0 0 0 0 0 3 0 0.000330 1 3.6e-06 0.97 6.6e-06 4.57e-08 5.52e-05
16 VCX2 variable charge, X-linked 2 46999 4 3 4 0 0 1 0 1 2 0 5.07e-06 0.67 0.00059 0.88 0.00059 6.16e-08 6.97e-05
17 RRAD Ras-related associated with diabetes 202274 4 4 1 0 0 0 0 4 0 0 0.00118 0.42 2e-07 0.0003 4.4e-06 1.04e-07 0.000111
18 ANKRD36 ankyrin repeat domain 36 752950 11 10 6 2 1 0 0 9 1 0 1.12e-05 0.52 0.00046 0.84 0.0013 2.79e-07 0.000280
19 KANK3 KN motif and ankyrin repeat domains 3 301372 6 6 2 0 0 0 0 0 6 0 6.92e-06 1 0.0011 0.37 0.0028 3.58e-07 0.000342
20 KRTAP1-1 keratin associated protein 1-1 157631 3 3 1 0 0 0 0 3 0 0 0.00432 0.62 4.4e-06 0.82 9e-06 7.03e-07 0.000636
21 UQCRFS1 ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1 180195 3 3 1 0 0 0 3 0 0 0 0.00524 0.31 5.8e-06 1 0.000011 1.02e-06 0.000879
22 ZCCHC3 zinc finger, CCHC domain containing 3 208403 3 3 1 0 0 0 0 0 3 0 0.00219 1 8e-07 0.99 0.000033 1.25e-06 0.00103
23 MADCAM1 mucosal vascular addressin cell adhesion molecule 1 158333 4 4 2 0 0 0 0 4 0 0 0.000511 0.35 0.000042 0.99 0.00031 2.61e-06 0.00206
24 CR1 complement component (3b/4b) receptor 1 (Knops blood group) 1444581 11 11 8 0 1 0 0 4 6 0 2.51e-05 0.095 0.016 0.037 0.0072 3.00e-06 0.00226
25 DACH2 dachshund homolog 2 (Drosophila) 506733 7 7 3 0 0 0 0 7 0 0 0.000117 0.27 0.0013 0.18 0.0027 5.00e-06 0.00362
26 NBPF10 neuroblastoma breakpoint family, member 10 1006919 26 20 18 6 2 2 6 16 0 0 0.000770 0.42 0.00016 1 0.00045 5.47e-06 0.00381
27 OR5H1 olfactory receptor, family 5, subfamily H, member 1 276592 5 4 3 1 0 2 1 0 2 0 0.000274 0.49 0.00088 0.55 0.0032 1.29e-05 0.00867
28 TSPAN19 tetraspanin 19 144817 4 4 4 0 0 0 1 1 2 0 6.30e-05 0.6 0.007 0.26 0.014 1.35e-05 0.00876
29 WDR52 WD repeat domain 52 887493 10 9 6 1 1 1 0 8 0 0 3.87e-05 0.35 0.066 0.045 0.024 1.41e-05 0.00879
30 KRT1 keratin 1 (epidermolytic hyperkeratosis) 500192 5 5 2 0 1 0 0 0 4 0 0.000790 0.72 0.00063 0.97 0.0018 2.08e-05 0.0125
31 MSN moesin 458269 4 4 4 0 1 0 0 2 1 0 0.00486 0.39 0.0033 0.031 0.0012 7.72e-05 0.0438
32 PCDHGA8 protocadherin gamma subfamily A, 8 835388 4 4 2 1 1 0 0 3 0 0 0.0957 0.61 2e-05 0.084 0.000062 7.74e-05 0.0438
33 BAGE2 B melanoma antigen family, member 2 101378 4 4 4 0 1 0 1 1 1 0 2.47e-05 0.29 0.1 0.82 0.34 0.000105 0.0577
34 ABCB1 ATP-binding cassette, sub-family B (MDR/TAP), member 1 1157641 9 8 9 0 0 0 4 3 2 0 0.00184 0.084 0.004 0.16 0.0047 0.000109 0.0579
35 POTEC POTE ankyrin domain family, member C 455476 10 10 6 3 6 0 3 1 0 0 4.50e-05 0.28 0.3 0.16 0.2 0.000112 0.0579
SV2C

Figure S1.  This figure depicts the distribution of mutations and mutation types across the SV2C significant gene.

TOR1A

Figure S2.  This figure depicts the distribution of mutations and mutation types across the TOR1A significant gene.

TPST1

Figure S3.  This figure depicts the distribution of mutations and mutation types across the TPST1 significant gene.

MTOR

Figure S4.  This figure depicts the distribution of mutations and mutation types across the MTOR significant gene.

EBPL

Figure S5.  This figure depicts the distribution of mutations and mutation types across the EBPL significant gene.

FAM174B

Figure S6.  This figure depicts the distribution of mutations and mutation types across the FAM174B significant gene.

RRAD

Figure S7.  This figure depicts the distribution of mutations and mutation types across the RRAD significant gene.

ANKRD36

Figure S8.  This figure depicts the distribution of mutations and mutation types across the ANKRD36 significant gene.

KRTAP1-1

Figure S9.  This figure depicts the distribution of mutations and mutation types across the KRTAP1-1 significant gene.

ZCCHC3

Figure S10.  This figure depicts the distribution of mutations and mutation types across the ZCCHC3 significant gene.

CR1

Figure S11.  This figure depicts the distribution of mutations and mutation types across the CR1 significant gene.

DACH2

Figure S12.  This figure depicts the distribution of mutations and mutation types across the DACH2 significant gene.

OR5H1

Figure S13.  This figure depicts the distribution of mutations and mutation types across the OR5H1 significant gene.

TSPAN19

Figure S14.  This figure depicts the distribution of mutations and mutation types across the TSPAN19 significant gene.

WDR52

Figure S15.  This figure depicts the distribution of mutations and mutation types across the WDR52 significant gene.

KRT1

Figure S16.  This figure depicts the distribution of mutations and mutation types across the KRT1 significant gene.

MSN

Figure S17.  This figure depicts the distribution of mutations and mutation types across the MSN significant gene.

PCDHGA8

Figure S18.  This figure depicts the distribution of mutations and mutation types across the PCDHGA8 significant gene.

ABCB1

Figure S19.  This figure depicts the distribution of mutations and mutation types across the ABCB1 significant gene.

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: 85. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 VHL von Hippel-Lindau tumor suppressor 150 537 150 157341 3740 0 0
2 PIK3CA phosphoinositide-3-kinase, catalytic, alpha polypeptide 14 184 12 53912 3014 0 0
3 TP53 tumor protein p53 13 308 12 90244 1649 0 0
4 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 16 728 16 213304 120 0 0
5 CHEK2 CHK2 checkpoint homolog (S. pombe) 7 2 4 586 4 7.3e-14 6.6e-11
6 NF1 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) 11 285 6 83505 8 3.6e-08 0.000026
7 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 4 51 4 14943 14813 4.1e-08 0.000026
8 ARHGAP20 Rho GTPase activating protein 20 4 2 2 586 2 7.7e-07 0.00043
9 NF2 neurofibromin 2 (merlin) 6 543 6 159099 36 1.5e-06 0.00076
10 SBNO1 strawberry notch homolog 1 (Drosophila) 3 4 2 1172 4 3.1e-06 0.0014

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 nmuts0 nmuts3 nmuts12 npairs0 npairs3 npairs12
8744 VHL von Hippel-Lindau tumor suppressor 143 0 125 401 986 125 401 986
5016 MUC4 mucin 4, cell surface associated 104 0 38 64 165 38 64 165
412 ANKRD36 ankyrin repeat domain 36 11 0 15 15 16 15 15 16
4722 MED12L mediator complex subunit 12-like 9 0 15 15 15 15 15 15
2449 EBPL emopamil binding protein-like 6 0 10 10 15 10 10 15
2093 DACH2 dachshund homolog 2 (Drosophila) 7 0 10 10 10 10 10 10
8818 WDR52 WD repeat domain 52 10 0 10 10 10 10 10 10
5149 NBPF10 neuroblastoma breakpoint family, member 10 26 0 7 11 11 7 11 11
6234 POTEC POTE ankyrin domain family, member C 10 0 7 7 8 7 7 8
742 BAP1 BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) 28 0 6 11 22 6 11 22

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: 5. 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_ns_s p q
1 HIFPATHWAY Under normal conditions, hypoxia inducible factor HIF-1 is degraded; under hypoxic conditions, it activates transcription of genes controlled by hpoxic response elements (HREs). ARNT, ASPH, COPS5, CREB1, EDN1, EP300, EPO, HIF1A, HSPCA, JUN, LDHA, NOS3, P4HB, VEGF, VHL 13 ASPH(1), EP300(6), HIF1A(3), JUN(1), NOS3(1), VHL(150) 7504580 162 151 108 8 2 15 18 39 88 0 9.3e-08 1.9e-15 7.9e-13
2 VEGFPATHWAY Vascular endothelial growth factor (VEGF) is upregulated by hypoxic conditions and promotes normal blood vessel formation and angiogenesis related to tumor growth or cardiac disease. ARNT, EIF1, EIF1A, EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5, EIF2S1, EIF2S2, EIF2S3, ELAVL1, FLT1, FLT4, HIF1A, HRAS, KDR, NOS3, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, PTK2, PXN, SHC1, VEGF, VHL 25 EIF1(1), EIF2B1(2), EIF2B2(1), EIF2B5(2), EIF2S1(1), EIF2S2(1), ELAVL1(1), FLT1(3), FLT4(4), HIF1A(3), KDR(5), NOS3(1), PIK3CA(14), PIK3R1(1), PTK2(1), PXN(2), SHC1(2), VHL(150) 14983008 195 165 140 17 7 18 26 53 91 0 2.9e-06 2.6e-15 7.9e-13
3 HSA04120_UBIQUITIN_MEDIATED_PROTEOLYSIS Genes involved in ubiquitin mediated proteolysis ANAPC1, ANAPC10, ANAPC11, ANAPC2, ANAPC4, ANAPC5, ANAPC7, BTRC, CDC16, CDC20, CDC23, CDC26, CDC27, CUL1, CUL2, CUL3, FBXW11, FBXW7, FZR1, ITCH, LOC728919, RBX1, SKP1, SKP2, SMURF1, SMURF2, TCEB1, TCEB2, UBA1, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2D4, UBE2E1, UBE2E2, UBE2E3, VHL, WWP1, WWP2 39 ANAPC1(4), ANAPC11(1), ANAPC2(1), ANAPC4(2), ANAPC5(2), ANAPC7(1), CDC16(2), CDC20(1), CDC23(2), CDC27(5), CUL1(3), CUL2(1), CUL3(2), FBXW11(1), FBXW7(4), FZR1(1), SKP2(1), SMURF1(1), SMURF2(2), TCEB1(1), UBA1(1), UBE2D1(2), UBE2D2(1), UBE2D3(1), UBE2E2(1), VHL(150), WWP1(1), WWP2(1) 17820449 196 165 142 21 4 19 31 48 94 0 0.000027 5.2e-15 1.1e-12
4 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 AKT1(1), AKT2(2), AKT3(2), MAPK1(1), MAPK3(1), PDK1(1), PIK3CA(14), PIK3CD(1), PTEN(16), PTK2B(2), RBL2(3), SHC1(2), SOS1(4) 8973555 50 45 49 5 3 5 19 14 9 0 0.0012 0.00026 0.04
5 SA_TRKA_RECEPTOR The TrkA receptor binds nerve growth factor to activate MAP kinase pathways and promote cell growth. AKT1, AKT2, AKT3, ARHA, CDKN1A, ELK1, GRB2, HRAS, MAP2K1, MAP2K2, NGFB, NGFR, NTRK1, PIK3CA, PIK3CD, SHC1, SOS1 15 AKT1(1), AKT2(2), AKT3(2), CDKN1A(1), ELK1(1), MAP2K1(1), NGFR(1), NTRK1(2), PIK3CA(14), PIK3CD(1), SHC1(2), SOS1(4) 7184719 32 31 31 2 2 3 13 13 1 0 0.0029 0.00076 0.094
6 BLYMPHOCYTEPATHWAY B cells express the major histocompatibility complex (class II MHC), immunoglobulins, adhesion proteins, and other factors on their cell surface. CD80, CR1, CR2, FCGR2B, HLA-DRA, HLA-DRB1, ICAM1, ITGAL, ITGB2, PTPRC, TNFRSF5 10 CD80(1), CR1(11), CR2(1), HLA-DRA(1), ITGAL(3), ITGB2(1), PTPRC(6) 6737962 24 23 21 2 2 0 2 11 9 0 0.091 0.014 1
7 HSA00950_ALKALOID_BIOSYNTHESIS_I Genes involved in alkaloid biosynthesis I DDC, GOT1, GOT2, TAT, TYR 5 DDC(3), GOT1(1), GOT2(3), TAT(1), TYR(1) 2063429 9 9 9 1 1 0 5 1 2 0 0.2 0.018 1
8 ACETAMINOPHENPATHWAY Acetaminophen selectively inhibits Cox-3, which is localized to the brain, and yields the toxic metabolite NAPQI when processed by CAR in the liver. CYP1A2, CYP2E1, CYP3A, NR1I3, PTGS1, PTGS2 5 CYP1A2(2), CYP2E1(2), NR1I3(1), PTGS2(4) 2332448 9 9 9 1 1 0 1 5 2 0 0.35 0.029 1
9 HSA00130_UBIQUINONE_BIOSYNTHESIS Genes involved in ubiquinone biosynthesis COQ2, COQ3, COQ5, COQ6, COQ7, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, NDUFA12, NDUFA13, NDUFB11 8 COQ5(2), COQ6(1), NDUFA13(3), NDUFB11(1) 1778759 7 7 7 0 2 0 1 3 1 0 0.15 0.046 1
10 CYSTEINE_METABOLISM CARS, CTH, GOT1, GOT2, LDHA, LDHB, LDHC, MPST 8 CARS(2), CTH(1), GOT1(1), GOT2(3), LDHB(1), LDHC(2), MPST(2) 3003190 12 12 12 2 2 0 4 3 3 0 0.33 0.051 1

Table 7.  Get Full Table A Ranked List of Significantly Mutated Genesets (Excluding Significantly Mutated Genes). Number of significant genesets found: 0. 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_ns_s p q
1 HSA00950_ALKALOID_BIOSYNTHESIS_I Genes involved in alkaloid biosynthesis I DDC, GOT1, GOT2, TAT, TYR 5 DDC(3), GOT1(1), GOT2(3), TAT(1), TYR(1) 2063429 9 9 9 1 1 0 5 1 2 0 0.2 0.018 1
2 ACETAMINOPHENPATHWAY Acetaminophen selectively inhibits Cox-3, which is localized to the brain, and yields the toxic metabolite NAPQI when processed by CAR in the liver. CYP1A2, CYP2E1, CYP3A, NR1I3, PTGS1, PTGS2 5 CYP1A2(2), CYP2E1(2), NR1I3(1), PTGS2(4) 2332448 9 9 9 1 1 0 1 5 2 0 0.35 0.029 1
3 HSA00130_UBIQUINONE_BIOSYNTHESIS Genes involved in ubiquinone biosynthesis COQ2, COQ3, COQ5, COQ6, COQ7, ND1, ND2, ND3, ND4, ND4L, ND5, ND6, NDUFA12, NDUFA13, NDUFB11 8 COQ5(2), COQ6(1), NDUFA13(3), NDUFB11(1) 1778759 7 7 7 0 2 0 1 3 1 0 0.15 0.046 1
4 CYSTEINE_METABOLISM CARS, CTH, GOT1, GOT2, LDHA, LDHB, LDHC, MPST 8 CARS(2), CTH(1), GOT1(1), GOT2(3), LDHB(1), LDHC(2), MPST(2) 3003190 12 12 12 2 2 0 4 3 3 0 0.33 0.051 1
5 HSA00272_CYSTEINE_METABOLISM Genes involved in cysteine metabolism CARS, CARS2, CDO1, CTH, GOT1, GOT2, LDHA, LDHAL6A, LDHAL6B, LDHB, LDHC, MPST, SDS, SULT1B1, SULT1C2, SULT1C4, SULT4A1 17 CARS(2), CARS2(3), CTH(1), GOT1(1), GOT2(3), LDHAL6B(1), LDHB(1), LDHC(2), MPST(2), SULT1C2(1), SULT4A1(1) 5521164 18 18 18 2 2 1 5 5 5 0 0.14 0.052 1
6 CYANOAMINO_ACID_METABOLISM ATP6V0C, SHMT1, GBA3, GGT1, SHMT1, SHMT2 5 GBA3(2), GGT1(1), SHMT1(2), SHMT2(2) 1851827 7 7 7 1 0 0 3 1 3 0 0.38 0.056 1
7 HSA00401_NOVOBIOCIN_BIOSYNTHESIS Genes involved in novobiocin biosynthesis GOT1, GOT2, TAT 3 GOT1(1), GOT2(3), TAT(1) 1153972 5 5 5 1 1 0 3 0 1 0 0.42 0.056 1
8 EEA1PATHWAY The FYVE-finger proteins EEA1 and HRS are localized to endosome membranes and regulate sorting and ubiquitination in the vesicle transport system. EEA1, EGF, EGFR, HGS, RAB5A, TF, TFRC 7 EEA1(5), EGF(3), EGFR(4), HGS(3), TF(1), TFRC(2) 5644686 18 18 18 2 2 2 6 5 3 0 0.1 0.064 1
9 BBCELLPATHWAY Fas ligand expression by T cells induces apoptosis in Fas-expressing, inactive B cells. CD28, CD4, HLA-DRA, HLA-DRB1, TNFRSF5, TNFRSF6, TNFSF5, TNFSF6 4 CD28(2), CD4(1), HLA-DRA(1) 1044308 4 4 4 0 1 1 0 1 1 0 0.42 0.083 1
10 METHANE_METABOLISM ADH5, ATP6V0C, SHMT1, CAT, EPX, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, SHMT1, SHMT2, TPO 13 ADH5(1), CAT(2), EPX(1), MPO(2), PRDX1(1), PRDX5(1), PRDX6(1), SHMT1(2), SHMT2(2), TPO(2) 5198189 15 15 15 1 1 2 5 5 2 0 0.056 0.089 1
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]

Download Results

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

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