Mutation Analysis (MutSigCV v0.9)
Stomach and Esophageal carcinoma (Primary solid tumor)
21 August 2015  |  analyses__2015_08_21
Maintainer Information
Citation Information
doi:10.7908/C16D5S9H
Maintained by David Heiman (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Mutation Analysis (MutSigCV v0.9). Broad Institute of MIT and Harvard. doi:10.7908/C16D5S9H
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. MutSigCV v0.9 was used to generate the results found in this report.

  • Working with individual set: STES-TP

  • Number of patients in set: 289

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:STES-TP.final_analysis_set.maf

  • Blacklist used for this analysis: pancan_mutation_blacklist.v14.hg19.txt

  • Significantly mutated genes (q ≤ 0.1): 78

Results
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). If the figure is unpopulated, then full coverage is assumed (e.g. MutSig CV doesn't use WIGs and assumes full coverage).

Figure 1. 

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

Figure 2.  Patients counts and rates file used to generate this plot: STES-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:

  • nnon = 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

  • nflank = number of noncoding mutations from this gene's flanking region, across the individual set

  • nsil = number of silent mutations in this gene across the individual set

  • p = p-value (overall)

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

Table 1.  Get Full Table A Ranked List of Significantly Mutated Genes. Number of significant genes found: 78. 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).

gene Nnon Nsil Nflank nnon npat nsite nsil nflank nnei fMLE p score time q
ARID1A 1290963 380324 3384 119 90 83 4 0 2 0.63 0 390 0.27 0
PIK3CA 751111 192185 3564 72 57 34 2 0 20 0.89 0 130 0.24 0
XYLT2 496791 153748 1584 35 32 10 3 0 16 0.63 5.6e-16 140 0.23 3.4e-12
TP53 273105 79764 1854 149 138 90 0 0 4 0.88 1.1e-15 500 0.24 5.1e-12
RNF43 481185 152303 1575 63 49 19 2 0 8 0.57 2.7e-15 240 0.24 9.7e-12
PTEN 281486 67626 1566 33 23 22 4 0 20 0.66 4.2e-15 100 0.24 1.3e-11
BZRAP1 1062653 338708 4590 47 46 17 5 0 2 1.2 9.4e-15 190 0.24 2.5e-11
B2M 82943 23120 576 30 17 18 1 0 20 0.69 1.1e-14 83 0.25 2.6e-11
GNG12 50864 13583 396 11 11 3 2 0 20 0.71 6e-14 57 0.23 1.2e-10
CDH1 564706 167909 3114 30 29 27 4 0 20 0.87 2.1e-10 99 0.23 3.8e-07
LMAN1 354025 95081 2268 19 19 4 2 3 10 1 7e-10 89 0.24 1.2e-06
PLEKHA6 585803 170221 3033 26 20 18 1 0 20 0.55 3.5e-09 85 0.25 5.3e-06
SMAD4 382636 106641 1998 28 24 23 1 0 20 1 1.2e-08 79 0.25 0.000017
OR5M3 204901 58089 225 16 15 9 1 0 20 0.85 1.3e-08 59 0.26 0.000017
MBD6 644759 244783 2115 31 23 18 2 0 20 1.1 1.5e-08 94 0.23 0.000018
FBXW7 561238 154037 2151 28 27 18 1 0 20 0.8 3.3e-08 80 0.25 0.000037
LARP4B 493901 145078 2961 29 27 8 2 0 2 0.66 5.3e-08 120 0.25 0.000057
EDNRB 306918 88145 3294 30 27 22 4 1 4 1.3 6.8e-08 90 0.25 0.000069
KLF3 236113 67915 936 23 19 15 1 0 7 1.1 7.9e-08 74 0.25 0.000074
APC 1928208 540430 2619 53 42 46 7 0 4 0.57 8.4e-08 140 0.26 0.000074
RHOA 191896 55777 999 17 16 13 0 1 20 0.55 8.8e-08 51 0.24 0.000074
CD4 302872 89012 1548 15 15 6 3 0 20 0.84 9.2e-08 63 0.26 0.000074
ATP6V1B1 340731 101439 2412 22 20 10 2 0 20 1.1 9.3e-08 80 0.26 0.000074
CTCF 509796 130628 1809 19 18 11 2 0 20 0.66 1e-07 72 0.25 0.000077
JARID2 812668 236113 3726 34 28 22 6 0 16 0.74 1.1e-07 95 0.24 0.000077
CCDC153 94214 26588 738 8 8 2 0 0 6 0.5 2.2e-07 43 0.24 0.00016
MUC6 1160913 408068 2385 45 34 40 12 0 20 1.1 4.3e-07 110 0.24 0.00029
CRYGA 121091 32657 576 10 10 3 3 0 20 0.99 6.8e-07 47 0.23 0.00044
PGM5 309519 91613 1620 29 25 7 0 0 20 0.84 8.1e-07 59 0.24 0.00051
GAS6 321368 92769 2178 16 16 9 5 0 9 0.76 9e-07 66 0.25 0.00055
CASP8 420784 98549 1917 18 18 15 1 0 20 0.95 9.4e-07 67 0.27 0.00055
GATA3 245361 78319 720 17 16 13 4 0 20 0.87 1.2e-06 56 0.24 0.0007
WSB2 275128 80342 1449 9 9 8 1 0 17 0.19 3.2e-06 32 0.26 0.0017
EPHA2 616726 182937 2565 25 23 20 3 0 16 0.43 3.2e-06 68 0.25 0.0017
HLA-A 236980 71672 1386 16 15 9 0 0 20 1.3 3.8e-06 62 0.25 0.002
ARID1A

Figure S1.  This figure depicts the distribution of mutations and mutation types across the ARID1A significant gene.

PIK3CA

Figure S2.  This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

XYLT2

Figure S3.  This figure depicts the distribution of mutations and mutation types across the XYLT2 significant gene.

TP53

Figure S4.  This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

RNF43

Figure S5.  This figure depicts the distribution of mutations and mutation types across the RNF43 significant gene.

PTEN

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

BZRAP1

Figure S7.  This figure depicts the distribution of mutations and mutation types across the BZRAP1 significant gene.

B2M

Figure S8.  This figure depicts the distribution of mutations and mutation types across the B2M significant gene.

GNG12

Figure S9.  This figure depicts the distribution of mutations and mutation types across the GNG12 significant gene.

CDH1

Figure S10.  This figure depicts the distribution of mutations and mutation types across the CDH1 significant gene.

LMAN1

Figure S11.  This figure depicts the distribution of mutations and mutation types across the LMAN1 significant gene.

PLEKHA6

Figure S12.  This figure depicts the distribution of mutations and mutation types across the PLEKHA6 significant gene.

SMAD4

Figure S13.  This figure depicts the distribution of mutations and mutation types across the SMAD4 significant gene.

OR5M3

Figure S14.  This figure depicts the distribution of mutations and mutation types across the OR5M3 significant gene.

MBD6

Figure S15.  This figure depicts the distribution of mutations and mutation types across the MBD6 significant gene.

FBXW7

Figure S16.  This figure depicts the distribution of mutations and mutation types across the FBXW7 significant gene.

LARP4B

Figure S17.  This figure depicts the distribution of mutations and mutation types across the LARP4B significant gene.

EDNRB

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

KLF3

Figure S19.  This figure depicts the distribution of mutations and mutation types across the KLF3 significant gene.

APC

Figure S20.  This figure depicts the distribution of mutations and mutation types across the APC significant gene.

RHOA

Figure S21.  This figure depicts the distribution of mutations and mutation types across the RHOA significant gene.

CD4

Figure S22.  This figure depicts the distribution of mutations and mutation types across the CD4 significant gene.

ATP6V1B1

Figure S23.  This figure depicts the distribution of mutations and mutation types across the ATP6V1B1 significant gene.

CTCF

Figure S24.  This figure depicts the distribution of mutations and mutation types across the CTCF significant gene.

JARID2

Figure S25.  This figure depicts the distribution of mutations and mutation types across the JARID2 significant gene.

CCDC153

Figure S26.  This figure depicts the distribution of mutations and mutation types across the CCDC153 significant gene.

MUC6

Figure S27.  This figure depicts the distribution of mutations and mutation types across the MUC6 significant gene.

CRYGA

Figure S28.  This figure depicts the distribution of mutations and mutation types across the CRYGA significant gene.

PGM5

Figure S29.  This figure depicts the distribution of mutations and mutation types across the PGM5 significant gene.

GAS6

Figure S30.  This figure depicts the distribution of mutations and mutation types across the GAS6 significant gene.

GATA3

Figure S31.  This figure depicts the distribution of mutations and mutation types across the GATA3 significant gene.

WSB2

Figure S32.  This figure depicts the distribution of mutations and mutation types across the WSB2 significant gene.

EPHA2

Figure S33.  This figure depicts the distribution of mutations and mutation types across the EPHA2 significant gene.

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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