Mutation Analysis (MutSigCV v0.9)
Brain Lower Grade Glioma (Primary solid tumor)
21 April 2013  |  analyses__2013_04_21
Maintainer Information
Citation Information
doi:10.7908/C16T0JMW
Maintained by Dan DiCara (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Brain Lower Grade Glioma (Primary solid tumor cohort) - 21 April 2013: Mutation Analysis (MutSigCV v0.9). Broad Institute of MIT and Harvard. doi:10.7908/C16T0JMW
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: LGG-TP

  • Number of patients in set: 217

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: 12. 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 205065 59892 824 151 113 78 2 0 4 3.3 1.1e-16 320 0.16 2e-12
IDH1 218519 56420 648 165 165 2 0 0 13 0.54 3.3e-16 510 0.17 3e-12
ATRX 1309595 323113 2844 104 93 92 3 0 1 1.8 2.6e-15 400 0.22 1.6e-11
CIC 676606 245210 1312 47 41 40 0 0 8 0.26 6.2e-15 160 0.17 2.8e-11
FUBP1 333963 98518 1584 22 22 21 2 0 5 1.7 8.5e-15 110 0.34 3.1e-11
NOTCH1 866481 250418 1520 29 19 26 3 0 20 1.2 1.4e-09 75 0.17 4.4e-06
IL32 88536 23219 436 6 6 1 0 0 20 1 4.7e-09 39 0.17 0.000011
PIK3R1 404488 103943 1380 15 14 13 1 0 20 1.7 4.7e-09 60 0.17 0.000011
PIK3CA 563983 144305 1584 21 19 13 0 0 20 1.3 1.7e-08 58 0.17 0.000034
PTEN 211358 50778 696 12 12 12 0 0 20 1.2 7.1e-08 43 0.18 0.00013
EMG1 147560 44919 492 4 4 2 0 0 20 0.68 0.000015 26 0.21 0.025
TIMD4 192913 59241 720 6 6 3 1 0 20 1 0.000036 30 0.15 0.055
IDH2 199206 52514 716 9 9 3 0 0 20 1 0.000074 29 0.16 0.1
CRIPAK 213528 70959 92 5 5 4 2 0 20 1 0.00017 25 0.3 0.22
TCF12 380401 108934 1604 10 9 9 0 0 7 3.5 0.00021 49 0.15 0.25
CREBZF 162967 55335 60 4 4 1 0 0 20 1.2 0.00044 25 0.29 0.48
NOX4 304234 81809 1404 6 5 3 0 0 13 0.92 0.00045 25 0.16 0.48
ARID1A 969339 285572 1504 16 13 16 0 0 2 0.44 0.0011 65 0.16 1
SMARCA4 702863 198772 2204 13 13 11 4 0 20 1.3 0.0015 42 0.28 1
ZNRF2 48391 12152 724 3 2 3 0 0 20 0.8 0.0017 12 0.12 1
ATG5 147343 35371 560 3 3 3 0 0 20 1.4 0.005 16 0.13 1
MUC7 179676 66836 176 8 5 7 0 0 20 0.94 0.0062 15 0.15 1
TRDN 189658 49259 988 4 4 4 0 0 14 2 0.012 19 0.22 1
TFAM 115661 27776 484 2 2 1 0 0 20 0.92 0.014 13 0.17 1
BTBD1 202895 52948 564 3 3 3 0 0 20 0.93 0.014 14 0.23 1
C3orf35 75516 23436 96 3 3 3 0 0 20 1.2 0.015 11 0.13 1
PRB2 191394 69657 212 4 4 3 1 0 12 1.6 0.015 16 0.15 1
EGFR 668360 182714 2352 12 10 9 0 0 20 0.42 0.016 25 0.15 1
GFRA4 18662 7161 108 1 1 1 0 0 20 1 0.02 7.1 0.16 1
SPANXN4 19530 4123 72 1 1 1 0 0 20 0.59 0.02 5.5 0.098 1
DDX5 318990 86800 1012 5 5 4 0 0 20 0.85 0.02 19 0.14 1
UQCRH 51429 12586 332 2 2 2 0 0 20 0 0.021 7.5 0.18 1
AP1S1 56203 14756 164 2 2 2 0 0 20 0.68 0.021 8.6 0.11 1
PAGE1 65100 17577 328 2 2 2 0 0 20 1.3 0.022 10 0.12 1
SPANXE 50778 13237 172 2 2 2 0 0 20 0.98 0.023 7.6 0.14 1
TP53

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

IDH1

Figure S2.  This figure depicts the distribution of mutations and mutation types across the IDH1 significant gene.

ATRX

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

CIC

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

FUBP1

Figure S5.  This figure depicts the distribution of mutations and mutation types across the FUBP1 significant gene.

NOTCH1

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

IL32

Figure S7.  This figure depicts the distribution of mutations and mutation types across the IL32 significant gene.

PIK3R1

Figure S8.  This figure depicts the distribution of mutations and mutation types across the PIK3R1 significant gene.

PIK3CA

Figure S9.  This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

PTEN

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

EMG1

Figure S11.  This figure depicts the distribution of mutations and mutation types across the EMG1 significant gene.

TIMD4

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