Mutation Analysis (MutSigCV v0.9)
Sarcoma (Primary solid tumor)
21 August 2015  |  analyses__2015_08_21
Maintainer Information
Citation Information
doi:10.7908/C1ZG6RJ4
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/C1ZG6RJ4
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: SARC-TP

  • Number of patients in set: 245

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:SARC-TP.final_analysis_set.maf

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

  • Significantly mutated genes (q ≤ 0.1): 9

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: SARC-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: 9. 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
TP53 231525 67620 108763 89 84 75 3 0 4 3.8 1.1e-16 330 0.24 2e-12
ATRX 1480105 365162 466986 40 37 40 0 2 1 1.1 5.8e-15 170 0.25 5.3e-11
RB1 699188 184352 408291 27 24 27 0 1 20 0.89 9.2e-15 130 0.65 5.6e-11
LOR 30727 9994 12499 6 6 2 2 0 20 1.4 1.3e-13 44 0.24 5.7e-10
NUMBL 153576 48919 72831 9 9 1 0 0 20 1.3 4.6e-13 56 0.22 1.7e-09
KRTAP5-5 130340 38220 22098 9 7 8 1 0 20 1.1 4.7e-10 40 0.39 1.4e-06
EOMES 261486 74684 75819 6 6 2 0 0 20 1 2e-06 34 0.27 0.0052
MMP3 279086 77563 123929 6 6 5 1 0 20 0.69 3.7e-06 29 0.21 0.0083
PTEN 236743 56871 113112 8 7 8 0 0 20 0.91 4.5e-06 30 0.23 0.0091
WWC1 585519 171847 282815 8 8 8 1 0 20 0.94 0.00013 33 0.23 0.23
DCDC1 213997 58116 109517 6 6 6 0 0 20 1.5 0.00014 23 0.24 0.23
CABLES1 248818 71489 132958 3 3 1 0 0 20 0.45 0.00022 20 0.27 0.34
PKD2 455945 122010 206973 6 6 3 0 0 20 1.3 0.0003 29 0.21 0.42
CCDC7 277606 66487 188617 5 5 5 1 0 11 0.67 0.0005 22 0.46 0.63
OR4S1 174338 52185 14418 5 5 5 0 0 20 1.5 0.00054 19 0.23 0.63
FOXD2 71642 22346 0 3 3 1 0 0 8 1.1 0.00055 19 0.23 0.63
OR8D1 171776 52522 13602 5 5 5 0 0 13 0.35 0.00092 17 0.2 0.93
SMARCAL1 539500 157290 234304 6 6 6 0 0 17 0.62 0.00092 27 0.81 0.93
NEFM 385599 109423 36964 5 5 5 0 0 20 0.29 0.00097 22 0.44 0.93
LHCGR 379648 109025 152431 6 6 4 0 0 6 1.6 0.001 30 0.34 0.93
LTBP3 537389 149522 238025 5 5 2 0 0 19 0.85 0.0015 28 0.48 1
SOX1 58667 16517 2888 2 2 1 0 0 20 1.2 0.0015 14 0.38 1
SCOC 74878 17936 83167 2 2 2 0 0 20 0.3 0.0018 11 0.18 1
SYNGR4 161465 51501 82816 3 3 3 0 0 20 0.66 0.0018 14 0.19 1
LYNX1 98438 31472 48335 2 2 2 0 0 20 0.73 0.002 13 0.24 1
COPS4 241366 63159 128825 4 4 4 1 0 20 0.62 0.002 16 0.36 1
ANP32E 150879 36066 96210 4 4 1 0 0 3 0 0.0022 24 0.66 1
F11R 175318 53410 138985 4 3 4 0 0 20 0.58 0.0024 16 0.49 1
EFCAB3 265253 67722 146904 4 4 4 0 0 20 0.72 0.0026 16 0.18 1
WDR18 114638 35106 49252 3 3 3 0 0 20 0.91 0.0026 14 0.31 1
SLC22A8 309190 95989 125795 5 5 5 0 0 20 0.63 0.0027 19 0.2 1
DAPK1 802091 230862 335981 6 6 6 0 2 20 0.43 0.0027 24 0.79 1
OR2V2 178166 52481 14275 4 4 4 1 0 20 1.5 0.0029 16 0.2 1
OS9 374013 106330 192633 5 4 5 3 0 20 0.63 0.003 19 0.23 1
SCN2A 1182175 315866 362917 11 11 11 0 0 16 1 0.0031 32 0.24 1
TP53

Figure S1.  This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

ATRX

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

RB1

Figure S3.  This figure depicts the distribution of mutations and mutation types across the RB1 significant gene.

LOR

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

NUMBL

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

KRTAP5-5

Figure S6.  This figure depicts the distribution of mutations and mutation types across the KRTAP5-5 significant gene.

EOMES

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

MMP3

Figure S8.  This figure depicts the distribution of mutations and mutation types across the MMP3 significant gene.

PTEN

Figure S9.  This figure depicts the distribution of mutations and mutation types across the PTEN 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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