Mutation Analysis (MutSigCV v0.9)
Glioblastoma Multiforme (Primary solid tumor)
23 May 2013  |  analyses__2013_05_23
Maintainer Information
Citation Information
doi:10.7908/C1CN71X6
Maintained by Dan DiCara (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Mutation Analysis (MutSigCV v0.9). Broad Institute of MIT and Harvard. doi:10.7908/C1CN71X6
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: GBM-TP

  • Number of patients in set: 284

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
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).

Figure 1. 

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

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

  • 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: 11. 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
PIK3R1 529376 136036 0 33 32 27 0 0 20 1.1 0 140 0.52 0
TP53 268380 78384 0 96 79 59 1 0 4 1 0 240 0.87 0
EGFR 874720 239128 0 92 74 44 7 0 20 1.6 2.3e-15 190 0.26 1.4e-11
PIK3CA 738116 188860 0 33 30 28 0 0 20 0.82 5.1e-15 100 0.56 1.9e-11
PTEN 276616 66456 0 90 87 73 0 0 20 0.44 5.2e-15 400 0.51 1.9e-11
RB1 808832 213284 0 25 24 22 1 0 20 0.79 6.7e-15 140 0.53 2e-11
NF1 2673008 749192 0 35 29 34 1 0 0 0.51 4.5e-08 130 1 0.00012
STAG2 887500 220384 0 12 12 12 0 0 20 0.71 3.8e-07 61 0.22 0.00086
IDH1 285988 73840 0 14 14 2 0 0 13 0.67 1.1e-06 43 0.25 0.0022
PRB2 250488 91164 0 6 6 2 0 0 12 1.5 2.5e-06 37 0.49 0.0046
GABRA6 307572 87188 0 11 11 10 1 0 20 1 0.000018 34 0.51 0.029
CDKN2C 111044 33796 0 3 3 3 0 0 20 0.94 0.00037 20 0.48 0.56
TPTE2 363804 94572 0 8 8 6 0 0 14 0.62 0.00054 32 0.75 0.75
CDC27 553232 149668 0 7 6 3 0 0 20 0.93 0.00073 32 0.64 0.9
RPL5 207320 53108 0 7 7 7 0 0 2 0.82 0.00074 34 0.5 0.9
OR5AR1 203628 59356 0 7 7 7 0 0 20 1.6 0.00085 22 0.49 0.91
LCE4A 66740 18176 0 2 2 1 0 0 20 0.17 0.00085 14 0.18 0.91
PSPH 167560 48280 0 5 5 3 0 0 19 0.94 0.0012 20 0.49 1
LZTR1 498704 142284 0 10 10 10 0 0 20 0.41 0.0012 31 0.22 1
LRRC55 221236 69296 0 6 6 6 1 0 20 1 0.0015 21 0.21 1
GFRA4 24424 9372 0 2 2 2 1 0 20 1.1 0.0016 11 0.4 1
QKI 252192 72420 0 5 5 5 0 0 12 0.31 0.0016 24 0.49 1
CHD8 1450956 415208 0 10 10 10 0 0 20 1 0.0035 45 0.26 1
BCOR 1012176 302744 0 8 8 8 3 0 20 0.91 0.0036 36 0.49 1
SEMA3C 512904 138876 0 11 11 11 1 0 11 1.8 0.0042 32 0.22 1
FOXR2 210444 53108 0 5 5 5 1 0 20 1.3 0.0043 16 0.25 1
KRTAP20-2 42600 12780 0 3 3 3 0 0 20 2.5 0.0048 13 0.21 1
OR5P2 208456 64752 0 4 4 3 0 0 20 1.3 0.0058 16 0.5 1
MTX3 154496 45156 0 3 3 3 0 0 20 0.52 0.0066 11 0.38 1
TXNDC3 412084 100252 0 6 5 6 1 0 20 1.4 0.0072 24 0.49 1
CD3EAP 330576 105364 0 3 3 1 0 0 20 0.19 0.0074 19 0.6 1
OR8K3 203628 60776 0 7 7 7 1 0 9 2.7 0.0076 24 0.5 1
ZNF697 117860 30388 0 3 3 3 0 0 20 0 0.0077 13 0.27 1
FOXG1 214136 67876 0 4 4 3 1 0 12 1.6 0.0081 22 0.26 1
LCE1F 77816 22436 0 3 3 3 1 0 20 1.4 0.0092 11 0.2 1
PIK3R1

Figure S1.  This figure depicts the distribution of mutations and mutation types across the PIK3R1 significant gene.

TP53

Figure S2.  This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

EGFR

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

PIK3CA

Figure S4.  This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

PTEN

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

RB1

Figure S6.  This figure depicts the distribution of mutations and mutation types across the RB1 significant gene.

NF1

Figure S7.  This figure depicts the distribution of mutations and mutation types across the NF1 significant gene.

STAG2

Figure S8.  This figure depicts the distribution of mutations and mutation types across the STAG2 significant gene.

IDH1

Figure S9.  This figure depicts the distribution of mutations and mutation types across the IDH1 significant gene.

GABRA6

Figure S10.  This figure depicts the distribution of mutations and mutation types across the GABRA6 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

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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