Mutation Analysis (MutSigCV v0.6)
Brain Lower Grade Glioma (Primary solid tumor)
22 February 2013  |  analyses__2013_02_22
Maintainer Information
Citation Information
doi:10.7908/C1P26WBG
Maintained by Dan DiCara (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Mutation Analysis (MutSigCV v0.6). Broad Institute of MIT and Harvard. doi:10.7908/C1P26WBG
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 v0.6 was used to generate the results found in this report.

  • Working with individual set: LGG-TP

  • Number of patients in set: 170

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: LGG-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: 14. 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 160650 46920 412 116 88 65 2 0 4 3.6 2e-15 260 0.16 2.4e-11
ATRX 1025950 253130 1422 82 73 73 2 0 1 1.3 3.8e-15 330 0.16 2.4e-11
IDH1 171190 44200 324 131 131 2 0 0 13 0.59 4e-15 420 0.16 2.4e-11
FUBP1 261630 77180 792 19 19 18 2 0 5 1.4 5.7e-15 98 0.16 2.6e-11
CIC 530060 192100 656 40 35 34 0 0 8 0.28 1.2e-14 150 0.17 4.3e-11
NOTCH1 678810 196180 760 25 16 22 2 0 20 1 1.1e-08 60 0.16 0.000035
PIK3R1 316880 81430 690 13 12 11 1 0 20 1.9 1.2e-07 48 0.15 0.0003
PIK3CA 441830 113050 792 15 15 10 0 0 20 1.3 1.3e-07 47 0.15 0.0003
ARID1A 759390 223720 752 14 11 14 0 0 2 0.49 6.1e-07 58 0.16 0.0012
IL32 69360 18190 218 4 4 1 0 0 20 0.92 7.5e-07 26 0.15 0.0014
PTEN 165580 39780 348 8 8 8 0 0 20 1.2 2.1e-06 32 0.15 0.0034
TIMD4 151130 46410 360 6 6 3 1 0 20 1.1 2.4e-06 31 0.15 0.0037
NOX4 238340 64090 702 6 5 3 0 0 13 0.88 0.000058 26 0.15 0.082
CRIPAK 167280 55590 46 5 5 4 2 0 20 1.1 0.000076 25 0.16 0.099
CREBZF 127670 43350 30 4 4 1 0 0 20 1.4 0.00011 25 0.16 0.14
HDAC2 196520 48790 510 4 4 4 0 0 6 0 0.00045 24 0.15 0.52
ZNRF2 37910 9520 362 3 2 3 0 0 20 0.73 0.00071 12 0.13 0.76
SCAF1 251260 81940 336 4 4 2 0 0 20 0.37 0.0011 19 0.14 1
EGFR 523600 143140 1176 10 8 8 0 0 20 0.46 0.0011 24 0.15 1
SMARCA4 550630 155720 1102 10 10 9 4 0 20 1.1 0.0014 32 0.15 1
UQCRH 40290 9860 166 2 2 2 0 0 20 0 0.0019 8.3 0.11 1
IDH2 156060 41140 358 6 6 2 0 0 20 1.1 0.0019 19 0.14 1
DDX5 249900 68000 506 5 5 4 0 0 20 0.75 0.0022 19 0.15 1
SERPINB7 156060 41310 286 4 4 4 0 0 8 0.62 0.0025 17 0.14 1
ATG5 115430 27710 280 3 3 3 0 0 20 1.5 0.0027 16 0.14 1
TCF12 298010 85340 802 6 6 5 0 0 7 3.4 0.003 33 0.15 1
FETUB 152660 46240 286 2 2 2 0 0 20 0.31 0.0032 13 0.14 1
KRT3 198730 58310 240 3 3 3 0 0 20 0.49 0.0036 16 0.14 1
NF1 1600040 448460 2368 21 11 20 1 0 0 0.45 0.004 46 0.16 1
PMEPA1 72250 22440 76 2 2 2 0 0 13 0 0.0041 11 0.12 1
SPDYE5 114920 30090 190 4 4 3 0 0 20 0.47 0.0043 12 0.13 1
MUC7 140760 52360 88 8 5 7 0 0 20 1 0.0046 14 0.14 1
EMG1 115600 35190 246 2 2 2 0 0 20 0.75 0.0047 13 0.14 1
C3orf35 59160 18360 48 3 3 3 0 0 20 1.3 0.0058 11 0.13 1
C12orf65 66640 19040 88 2 2 2 0 0 20 0.42 0.0069 10 0.12 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.

IDH1

Figure S3.  This figure depicts the distribution of mutations and mutation types across the IDH1 significant gene.

FUBP1

Figure S4.  This figure depicts the distribution of mutations and mutation types across the FUBP1 significant gene.

CIC

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

NOTCH1

Figure S6.  This figure depicts the distribution of mutations and mutation types across the NOTCH1 significant gene.

PIK3R1

Figure S7.  This figure depicts the distribution of mutations and mutation types across the PIK3R1 significant gene.

PIK3CA

Figure S8.  This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

ARID1A

Figure S9.  This figure depicts the distribution of mutations and mutation types across the ARID1A significant gene.

IL32

Figure S10.  This figure depicts the distribution of mutations and mutation types across the IL32 significant gene.

PTEN

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

TIMD4

Figure S12.  This figure depicts the distribution of mutations and mutation types across the TIMD4 significant gene.

NOX4

Figure S13.  This figure depicts the distribution of mutations and mutation types across the NOX4 significant gene.

CRIPAK

Figure S14.  This figure depicts the distribution of mutations and mutation types across the CRIPAK 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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