Mutation Analysis (MutSig v2.0)
Kidney Renal Papillary Cell Carcinoma (Primary solid tumor)
Due to issues with GAF 3.0, we strongly advise caution in the use of these results.
23 September 2013  |  analyses__2013_09_23
Maintainer Information
Citation Information
doi:10.7908/C1KW5DC3
Maintained by Dan DiCara (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Mutation Analysis (MutSig v2.0). Broad Institute of MIT and Harvard. doi:10.7908/C1KW5DC3
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: KIRP-TP

  • Number of patients in set: 112

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:KIRP-TP.final_analysis_set.maf

  • Significantly mutated genes (q ≤ 0.1): 18

  • Mutations seen in COSMIC: 43

  • Significantly mutated genes in COSMIC territory: 11

  • Genes with clustered mutations (≤ 3 aa apart): 72

  • Significantly mutated genesets: 0

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

Mutation Preprocessing

  • Read 112 MAFs of type "Broad"

  • Total number of mutations in input MAFs: 10029

  • After removing 78 mutations outside chr1-24: 9951

  • After removing 285 noncoding mutations: 9666

  • After collapsing adjacent/redundant mutations: 8213

Mutation Filtering

  • Number of mutations before filtering: 8213

  • After removing 413 mutations outside gene set: 7800

  • After removing 9 mutations outside category set: 7791

  • After removing 2 "impossible" mutations in

  • gene-patient-category bins of zero coverage: 7367

Results
Breakdown of Mutations by Type

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

type count
Frame_Shift_Del 511
Frame_Shift_Ins 199
In_Frame_Del 166
In_Frame_Ins 38
Missense_Mutation 4569
Nonsense_Mutation 248
Nonstop_Mutation 7
Silent 1705
Splice_Site 345
Translation_Start_Site 3
Total 7791
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 477 186386483 2.6e-06 2.6 1.4 2.1
*Cp(A/C/T)->T 863 1509673770 5.7e-07 0.57 0.31 1.7
A->G 861 1622585631 5.3e-07 0.53 0.29 2.3
transver 2368 3318645884 7.1e-07 0.71 0.39 5
indel+null 1506 3318645884 4.5e-07 0.45 0.25 NaN
double_null 9 3318645884 2.7e-09 0.0027 0.0015 NaN
Total 6084 3318645884 1.8e-06 1.8 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: KIRP-TP.patients.counts_and_rates.txt

Lego Plots

The mutation spectrum is depicted in the lego plots below in which the 96 possible mutation types are subdivided into six large blocks, color-coded to reflect the base substitution type. Each large block is further subdivided into the 16 possible pairs of 5' and 3' neighbors, as listed in the 4x4 trinucleotide context legend. The height of each block corresponds to the mutation frequency for that kind of mutation (counts of mutations normalized by the base coverage in a given bin). The shape of the spectrum is a signature for dominant mutational mechanisms in different tumor types.

Figure 3.  Get High-res Image SNV Mutation rate lego plot for entire set. Each bin is normalized by base coverage for that bin. Colors represent the six SNV types on the upper right. The three-base context for each mutation is labeled in the 4x4 legend on the lower right. The fractional breakdown of SNV counts is shown in the pie chart on the upper left. If this figure is blank, not enough information was provided in the MAF to generate it.

Figure 4.  Get High-res Image SNV Mutation rate lego plots for 4 slices of mutation allele fraction (0<=AF<0.1, 0.1<=AF<0.25, 0.25<=AF<0.5, & 0.5<=AF) . The color code and three-base context legends are the same as the previous figure. If this figure is blank, not enough information was provided in the MAF to generate it.

CoMut Plot

Figure 5.  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: *Cp(A/C/T)->T

  • n3 = number of nonsilent mutations of type: A->G

  • 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_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: 18. 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_clust p_cons p_joint p q
1 CDC27 cell division cycle 27 homolog (S. cerevisiae) 280332 4 4 1 0 0 0 0 0 4 0 0.00082 1 6e-07 0.078 0 <1.00e-15 <9.06e-12
2 KCNK5 potassium channel, subfamily K, member 5 159653 2 2 2 0 0 0 0 0 2 0 0.0075 0.33 0.26 0 0 <1.00e-15 <9.06e-12
3 PLAC4 placenta-specific 4 20310 5 4 4 0 0 0 1 0 4 0 1.2e-09 0.74 0.52 0.0016 0.0044 1.37e-10 6.24e-07
4 MET met proto-oncogene (hepatocyte growth factor receptor) 478818 9 9 8 0 0 3 2 4 0 0 7.7e-08 0.065 0.00038 0.0011 0.000066 1.38e-10 6.24e-07
5 MUC4 mucin 4, cell surface associated 365020 12 11 9 1 1 2 2 7 0 0 3e-10 0.12 NaN NaN NaN 3.04e-10 1.10e-06
6 IL32 interleukin 32 62375 4 4 2 0 0 0 0 0 4 0 3.8e-06 1 0.000021 0.9 0.0002 1.71e-08 5.17e-05
7 NF2 neurofibromin 2 (merlin) 181882 7 7 7 0 0 0 0 0 7 0 2.4e-08 0.43 0.43 0.98 0.59 2.73e-07 0.000707
8 NBPF1 neuroblastoma breakpoint family, member 1 371646 8 7 2 0 0 1 0 0 7 0 1.3e-06 0.021 NaN NaN NaN 1.30e-06 0.00294
9 PPARGC1B peroxisome proliferator-activated receptor gamma, coactivator 1 beta 320747 3 3 1 0 0 0 0 0 3 0 0.02 1 0.000092 0.00038 7.4e-06 2.45e-06 0.00494
10 FOXE1 forkhead box E1 (thyroid transcription factor 2) 51983 3 3 1 0 0 0 0 0 3 0 0.000045 1 0.00035 0.61 0.0049 3.60e-06 0.00653
11 KRTAP4-11 keratin associated protein 4-11 60031 4 4 3 1 0 0 2 2 0 0 3.3e-07 0.83 0.36 0.85 0.77 4.14e-06 0.00682
12 LGI4 leucine-rich repeat LGI family, member 4 78713 4 4 4 0 0 1 1 2 0 0 7.2e-06 0.28 0.35 0.015 0.046 5.22e-06 0.00789
13 NUDT11 nudix (nucleoside diphosphate linked moiety X)-type motif 11 47767 3 3 2 0 1 0 0 0 2 0 0.000037 0.61 0.0069 0.88 0.022 1.20e-05 0.0167
14 HRCT1 histidine rich carboxyl terminus 1 34801 3 3 2 0 0 0 0 2 1 0 0.000023 0.6 0.019 0.96 0.068 2.25e-05 0.0278
15 STAG3L2 stromal antigen 3-like 2 30982 3 3 1 0 0 0 0 0 3 0 0.000023 1 NaN NaN NaN 2.30e-05 0.0278
16 UBXN11 UBX domain protein 11 169165 4 3 2 0 0 0 0 0 4 0 0.0029 1 0.00029 0.2 0.00075 3.03e-05 0.0343
17 BHMT betaine-homocysteine methyltransferase 139714 4 4 4 0 0 0 2 0 2 0 0.000026 0.31 0.28 0.11 0.22 7.42e-05 0.0791
18 PCDHGC5 protocadherin gamma subfamily C, 5 324524 15 13 15 6 0 3 4 3 4 1 0.000078 0.67 NaN NaN NaN 7.85e-05 0.0791
19 ACSBG2 acyl-CoA synthetase bubblegum family member 2 226349 3 3 1 0 0 0 0 3 0 0 0.0077 0.61 0.000081 1 0.0011 0.000110 0.105
20 PARD6B par-6 partitioning defective 6 homolog beta (C. elegans) 118830 4 4 4 0 0 0 2 0 2 0 0.000016 0.26 0.63 0.71 0.91 0.000181 0.164
21 ATP1B1 ATPase, Na+/K+ transporting, beta 1 polypeptide 104177 4 4 4 0 0 0 1 1 2 0 0.000032 0.61 0.93 0.22 0.56 0.000212 0.183
22 NFE2L2 nuclear factor (erythroid-derived 2)-like 2 199571 3 3 3 0 0 0 1 2 0 0 0.0039 0.46 0.024 0.011 0.005 0.000229 0.189
23 OR2T35 olfactory receptor, family 2, subfamily T, member 35 33964 2 2 1 0 0 0 0 0 2 0 0.000065 1 0.015 0.92 0.45 0.000336 0.265
24 FAT1 FAT tumor suppressor homolog 1 (Drosophila) 1538743 8 8 8 1 1 0 2 2 3 0 0.006 0.5 0.003 0.48 0.0057 0.000388 0.290
25 SAV1 salvador homolog 1 (Drosophila) 129761 3 3 3 0 0 1 0 0 2 0 0.0002 0.74 0.1 0.97 0.18 0.000400 0.290
26 COCH coagulation factor C homolog, cochlin (Limulus polyphemus) 186274 4 4 4 0 1 0 1 2 0 0 9e-05 0.31 0.7 0.18 0.58 0.000570 0.393
27 POMC proopiomelanocortin (adrenocorticotropin/ beta-lipotropin/ alpha-melanocyte stimulating hormone/ beta-melanocyte stimulating hormone/ beta-endorphin) 64181 3 3 3 0 1 0 0 1 1 0 0.00015 0.52 0.3 0.5 0.38 0.000620 0.393
28 POTEC POTE ankyrin domain family, member C 167445 3 3 3 0 1 1 0 0 1 0 0.00024 0.35 0.12 0.38 0.24 0.000620 0.393
29 EPSTI1 epithelial stromal interaction 1 (breast) 143344 3 2 3 0 0 1 0 2 0 0 0.0074 0.48 0.0017 0.38 0.0079 0.000629 0.393
30 SETD2 SET domain containing 2 712734 7 7 7 0 0 0 0 2 5 0 0.00018 0.38 0.36 0.26 0.34 0.000654 0.395
31 CD86 CD86 molecule 113374 3 3 3 0 1 0 0 1 1 0 0.00018 0.6 0.31 0.093 0.38 0.000719 0.406
32 CUL3 cullin 3 261328 5 4 5 1 0 1 1 1 2 0 0.00073 0.59 0.072 0.6 0.097 0.000750 0.406
33 EBF2 early B-cell factor 2 193894 3 3 3 1 0 0 0 3 0 0 0.0057 0.8 0.0069 0.23 0.013 0.000757 0.406
34 OR8I2 olfactory receptor, family 8, subfamily I, member 2 103742 3 3 3 0 1 0 0 1 1 0 0.00031 0.49 0.27 0.17 0.23 0.000762 0.406
35 EEF1B2 eukaryotic translation elongation factor 1 beta 2 78624 2 2 1 0 0 0 2 0 0 0 0.0013 0.42 0.013 1 0.059 0.000794 0.411
CDC27

Figure S1.  This figure depicts the distribution of mutations and mutation types across the CDC27 significant gene.

KCNK5

Figure S2.  This figure depicts the distribution of mutations and mutation types across the KCNK5 significant gene.

PLAC4

Figure S3.  This figure depicts the distribution of mutations and mutation types across the PLAC4 significant gene.

MET

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

MUC4

Figure S5.  This figure depicts the distribution of mutations and mutation types across the MUC4 significant gene.

IL32

Figure S6.  This figure depicts the distribution of mutations and mutation types across the IL32 significant gene.

NF2

Figure S7.  This figure depicts the distribution of mutations and mutation types across the NF2 significant gene.

NBPF1

Figure S8.  This figure depicts the distribution of mutations and mutation types across the NBPF1 significant gene.

PPARGC1B

Figure S9.  This figure depicts the distribution of mutations and mutation types across the PPARGC1B significant gene.

FOXE1

Figure S10.  This figure depicts the distribution of mutations and mutation types across the FOXE1 significant gene.

KRTAP4-11

Figure S11.  This figure depicts the distribution of mutations and mutation types across the KRTAP4-11 significant gene.

LGI4

Figure S12.  This figure depicts the distribution of mutations and mutation types across the LGI4 significant gene.

NUDT11

Figure S13.  This figure depicts the distribution of mutations and mutation types across the NUDT11 significant gene.

HRCT1

Figure S14.  This figure depicts the distribution of mutations and mutation types across the HRCT1 significant gene.

UBXN11

Figure S15.  This figure depicts the distribution of mutations and mutation types across the UBXN11 significant gene.

BHMT

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

PCDHGC5

Figure S17.  This figure depicts the distribution of mutations and mutation types across the PCDHGC5 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: 11. Number of genes displayed: 10

rank gene description n cos n_cos N_cos cos_ev p q
1 MET met proto-oncogene (hepatocyte growth factor receptor) 9 34 4 3808 12 9.8e-11 4.4e-07
2 FGFR3 fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism) 5 62 3 6944 1469 3.4e-07 0.00077
3 NF2 neurofibromin 2 (merlin) 7 550 4 61600 29 6.2e-06 0.0093
4 SMARCA4 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 5 30 2 3360 3 0.000019 0.021
5 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 2 52 2 5824 29208 0.000057 0.051
6 BRAF v-raf murine sarcoma viral oncogene homolog B1 2 89 2 9968 14380 0.00016 0.084
7 CDCA8 cell division cycle associated 8 1 1 1 112 1 0.00021 0.084
8 FLCN folliculin 1 1 1 112 1 0.00021 0.084
9 G6PC glucose-6-phosphatase, catalytic subunit 1 1 1 112 1 0.00021 0.084
10 PLXDC2 plexin domain containing 2 1 1 1 112 1 0.00021 0.084

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
2368 MUC4 mucin 4, cell surface associated 12 0 6 6 15 6 6 15
54 ACSBG2 acyl-CoA synthetase bubblegum family member 2 3 0 3 3 3 3 3 3
4435 ZNF814 zinc finger protein 814 6 0 3 3 3 3 3 3
2259 MET met proto-oncogene (hepatocyte growth factor receptor) 9 0 1 3 4 1 3 4
2745 PCF11 PCF11, cleavage and polyadenylation factor subunit, homolog (S. cerevisiae) 8 0 1 2 10 1 2 10
1219 EP400 E1A binding protein p400 6 0 1 2 2 1 2 2
1239 EPSTI1 epithelial stromal interaction 1 (breast) 3 0 1 1 3 1 1 3
2032 KRTAP4-9 keratin associated protein 4-9 3 0 1 1 3 1 1 3
92 ADAMTS7 ADAM metallopeptidase with thrombospondin type 1 motif, 7 3 0 1 1 1 1 1 1
199 ANAPC5 anaphase promoting complex subunit 5 3 0 1 1 1 1 1 1

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: 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 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(2), EIF4G1(2), EIF4G3(5), PIK3CA(2), PIK3R1(1), PTEN(2), TSC1(2), TSC2(4) 4653778 21 18 21 2 2 6 3 4 6 0 0.056 0.001 0.61
2 KREBPATHWAY The Krebs (citric acid) cycle takes place in mitochondria, where it extracts energy in the form of electron carriers NADH and FADH2, which drive the electron transport chain. ACO2, CS, FH, IDH2, MDH1, OGDH, SDHA, SUCLA2 8 FH(1), IDH2(1), MDH1(1), OGDH(2), SDHA(3) 1572837 8 8 8 0 0 3 1 1 3 0 0.052 0.0025 0.62
3 ALANINE_AND_ASPARTATE_METABOLISM AARS, ABAT, ADSL, ADSS, AGXT, AGXT2, ASL, ASNS, ASPA, ASS, CAD, CRAT, DARS, DDO, GAD1, GAD2, GOT1, GOT2, GPT, GPT2, NARS, PC 21 AARS(1), ADSL(1), AGXT(1), AGXT2(1), ASNS(1), CAD(3), CRAT(1), DARS(3), DDO(1), GPT(2), PC(4) 4376807 19 17 19 1 0 3 1 8 7 0 0.078 0.003 0.62
4 CBLPATHWAY Activated EGF receptors undergo endocytosis into clathrin-coated vesicles, where they are recycled to the membrane or ubiquitinated by Cbl. CBL, CSF1R, EGF, EGFR, GRB2, MET, PDGFRA, PRKCA, PRKCB1, SH3GLB1, SH3GLB2, SH3KBP1, SRC 12 CSF1R(1), EGF(1), MET(9), PDGFRA(2) 3254544 13 12 12 1 1 3 2 6 1 0 0.11 0.0063 0.96
5 CITRATE_CYCLE_TCA_CYCLE ACO1, ACO2, CS, DLD, DLST, DLSTP, FH, IDH1, IDH2, IDH3A, IDH3B, IDH3G, MDH1, MDH2, PC, PCK1, SDHA, SDHA, SDHAL2, SDHB, SUCLA2, SUCLG1, SUCLG2 20 ACO1(1), DLD(1), FH(1), IDH2(1), MDH1(1), PC(4), PCK1(1), SDHA(3) 3444763 13 12 13 0 0 2 2 3 6 0 0.035 0.013 1
6 DNAFRAGMENTPATHWAY DNA fragmentation during apoptosis is effected by DFF, a caspase-activated DNAse, and by endonuclease G. CASP3, CASP7, DFFA, DFFB, ENDOG, GZMB, HMGB1, HMGB2, TOP2A, TOP2B 9 HMGB1(3), HMGB2(2), TOP2B(3) 1518294 8 7 8 0 1 1 1 3 2 0 0.21 0.016 1
7 HSA00830_RETINOL_METABOLISM Genes involved in retinol metabolism ALDH1A1, ALDH1A2, BCMO1, RDH5 4 BCMO1(2), RDH5(2) 649405 4 4 4 1 0 0 3 0 1 0 0.72 0.018 1
8 HSA00252_ALANINE_AND_ASPARTATE_METABOLISM Genes involved in alanine and aspartate metabolism AARS, AARS2, ABAT, ACY3, ADSL, ADSS, ADSSL1, AGXT, AGXT2, ASL, ASNS, ASPA, ASRGL1, ASS1, CAD, CRAT, DARS, DARS2, DDO, DLAT, DLD, GAD1, GAD2, GOT1, GOT2, GPT, GPT2, NARS, NARS2, PC, PDHA1, PDHA2, PDHB 33 AARS(1), AARS2(1), ACY3(1), ADSL(1), AGXT(1), AGXT2(1), ASNS(1), CAD(3), CRAT(1), DARS(3), DDO(1), DLD(1), GPT(2), PC(4) 6354267 22 19 22 1 0 3 2 9 8 0 0.039 0.019 1
9 RABPATHWAY Rab family GTPases regulate vesicle transport, endocytosis and exocytosis, and vesicle docking via interactions with the rabphilins. ACTA1, MEL, RAB11A, RAB1A, RAB2, RAB27A, RAB3A, RAB4A, RAB5A, RAB6A, RAB7, RAB9A 9 ACTA1(1), RAB11A(1), RAB3A(1), RAB6A(1) 711732 4 4 4 1 0 1 0 2 1 0 0.81 0.022 1
10 HSA01040_POLYUNSATURATED_FATTY_ACID_BIOSYNTHESIS Genes involved in polyunsaturated fatty acid biosynthesis ACAA1, ACOX1, ACOX3, ELOVL2, ELOVL5, ELOVL6, FADS1, FADS2, FASN, GPSN2, HADHA, HSD17B12, PECR, SCD 13 ACAA1(3), ACOX1(1), ACOX3(2), ELOVL6(1), FADS1(1), FASN(3), HADHA(1) 2460627 12 9 12 1 1 4 0 6 1 0 0.096 0.022 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 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(2), EIF4G1(2), EIF4G3(5), PIK3CA(2), PIK3R1(1), PTEN(2), TSC1(2), TSC2(4) 4653778 21 18 21 2 2 6 3 4 6 0 0.056 0.001 0.61
2 KREBPATHWAY The Krebs (citric acid) cycle takes place in mitochondria, where it extracts energy in the form of electron carriers NADH and FADH2, which drive the electron transport chain. ACO2, CS, FH, IDH2, MDH1, OGDH, SDHA, SUCLA2 8 FH(1), IDH2(1), MDH1(1), OGDH(2), SDHA(3) 1572837 8 8 8 0 0 3 1 1 3 0 0.052 0.0025 0.62
3 ALANINE_AND_ASPARTATE_METABOLISM AARS, ABAT, ADSL, ADSS, AGXT, AGXT2, ASL, ASNS, ASPA, ASS, CAD, CRAT, DARS, DDO, GAD1, GAD2, GOT1, GOT2, GPT, GPT2, NARS, PC 21 AARS(1), ADSL(1), AGXT(1), AGXT2(1), ASNS(1), CAD(3), CRAT(1), DARS(3), DDO(1), GPT(2), PC(4) 4376807 19 17 19 1 0 3 1 8 7 0 0.078 0.003 0.62
4 CITRATE_CYCLE_TCA_CYCLE ACO1, ACO2, CS, DLD, DLST, DLSTP, FH, IDH1, IDH2, IDH3A, IDH3B, IDH3G, MDH1, MDH2, PC, PCK1, SDHA, SDHA, SDHAL2, SDHB, SUCLA2, SUCLG1, SUCLG2 20 ACO1(1), DLD(1), FH(1), IDH2(1), MDH1(1), PC(4), PCK1(1), SDHA(3) 3444763 13 12 13 0 0 2 2 3 6 0 0.035 0.013 1
5 DNAFRAGMENTPATHWAY DNA fragmentation during apoptosis is effected by DFF, a caspase-activated DNAse, and by endonuclease G. CASP3, CASP7, DFFA, DFFB, ENDOG, GZMB, HMGB1, HMGB2, TOP2A, TOP2B 9 HMGB1(3), HMGB2(2), TOP2B(3) 1518294 8 7 8 0 1 1 1 3 2 0 0.21 0.016 1
6 HSA00830_RETINOL_METABOLISM Genes involved in retinol metabolism ALDH1A1, ALDH1A2, BCMO1, RDH5 4 BCMO1(2), RDH5(2) 649405 4 4 4 1 0 0 3 0 1 0 0.72 0.018 1
7 HSA00252_ALANINE_AND_ASPARTATE_METABOLISM Genes involved in alanine and aspartate metabolism AARS, AARS2, ABAT, ACY3, ADSL, ADSS, ADSSL1, AGXT, AGXT2, ASL, ASNS, ASPA, ASRGL1, ASS1, CAD, CRAT, DARS, DARS2, DDO, DLAT, DLD, GAD1, GAD2, GOT1, GOT2, GPT, GPT2, NARS, NARS2, PC, PDHA1, PDHA2, PDHB 33 AARS(1), AARS2(1), ACY3(1), ADSL(1), AGXT(1), AGXT2(1), ASNS(1), CAD(3), CRAT(1), DARS(3), DDO(1), DLD(1), GPT(2), PC(4) 6354267 22 19 22 1 0 3 2 9 8 0 0.039 0.019 1
8 RABPATHWAY Rab family GTPases regulate vesicle transport, endocytosis and exocytosis, and vesicle docking via interactions with the rabphilins. ACTA1, MEL, RAB11A, RAB1A, RAB2, RAB27A, RAB3A, RAB4A, RAB5A, RAB6A, RAB7, RAB9A 9 ACTA1(1), RAB11A(1), RAB3A(1), RAB6A(1) 711732 4 4 4 1 0 1 0 2 1 0 0.81 0.022 1
9 HSA01040_POLYUNSATURATED_FATTY_ACID_BIOSYNTHESIS Genes involved in polyunsaturated fatty acid biosynthesis ACAA1, ACOX1, ACOX3, ELOVL2, ELOVL5, ELOVL6, FADS1, FADS2, FASN, GPSN2, HADHA, HSD17B12, PECR, SCD 13 ACAA1(3), ACOX1(1), ACOX3(2), ELOVL6(1), FADS1(1), FASN(3), HADHA(1) 2460627 12 9 12 1 1 4 0 6 1 0 0.096 0.022 1
10 UBIQUINONE_BIOSYNTHESIS NDUFA1, NDUFA10, NDUFA11, NDUFA4, NDUFA5, NDUFA8, NDUFB2, NDUFB4, NDUFB5, NDUFB6, NDUFB7, NDUFS1, NDUFS2, NDUFV1, NDUFV2 15 NDUFA10(1), NDUFB2(1), NDUFB5(1), NDUFS1(2), NDUFV1(1) 1169848 6 6 6 0 0 1 0 3 2 0 0.32 0.023 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

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

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