Mutation Analysis (MutSigCV v0.6)
Lung Adenocarcinoma (MOLECULAR_NONSMOKER)
07 February 2013  |  awg_luad__2013_02_07
Maintainer Information
Citation Information
doi:10.7908/C1NP22JM
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/C1NP22JM
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: MOLECULAR_NONSMOKER

  • Number of patients in set: 56

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: MOLECULAR_NONSMOKER.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: 6. 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 52920 15456 75544 21 19 17 0 0 4 0 3.8e-15 95 0.057 6.9e-11
EGFR 172088 47040 379008 12 10 7 0 3 20 0.74 9.3e-11 40 0.053 8.4e-07
SMAD4 74368 20720 107968 6 6 5 0 1 20 0.56 5.4e-09 28 0.05 0.000033
CDKN2A 21056 6216 15064 5 5 5 0 0 6 2.2 2.3e-07 25 0.051 0.001
KEAP1 73808 21616 38920 6 6 6 0 0 20 0.42 2.1e-06 20 0.052 0.0078
BRAF 96992 27720 211120 7 7 4 0 0 19 0.5 4.1e-06 20 0.049 0.013
ZNF566 58016 13272 52808 3 3 2 0 0 20 0.26 0.000042 16 0.047 0.11
CRIPAK 55776 18536 13216 3 3 2 1 0 20 0.71 0.000067 16 0.05 0.15
NAA15 116032 27832 179424 3 3 2 0 0 20 0.43 0.00016 15 0.046 0.33
DCT 71848 20048 94528 2 2 2 0 0 19 0.32 0.00018 13 0.047 0.33
ERBB2 161728 49616 252616 3 3 2 0 0 6 0 0.00022 17 0.049 0.37
EIF5B 165872 40712 246512 6 3 5 0 0 3 0 0.00027 15 0.047 0.41
FRMD8 42560 13496 68208 4 4 3 0 0 20 1 0.00033 14 0.047 0.47
CETN3 23576 5432 59808 2 2 1 0 0 20 1.4 0.00043 12 0.045 0.53
C12orf74 24920 8008 18368 2 2 1 0 2 20 2.1 0.00044 13 0.047 0.53
CBWD1 41104 10808 120848 2 2 1 0 0 5 0.71 0.00048 13 0.047 0.55
U2AF1 35280 9576 98336 2 2 1 0 0 20 0.12 0.00059 7.8 0.038 0.59
MST1 101080 29848 110768 3 3 2 1 1 20 0.88 0.0006 15 0.047 0.59
SEC61A1 62776 19432 135856 2 2 1 0 0 20 0.89 0.00062 13 0.045 0.59
CASP8 81704 19096 107072 4 2 2 0 0 20 0.78 0.0007 13 0.049 0.62
SETD2 280224 75152 227416 8 6 7 0 1 7 3 0.00077 31 0.052 0.62
FAM75A2 54264 15736 24640 2 2 2 0 0 8 0 0.00077 10 0.042 0.62
STK11 30576 8792 27328 3 3 3 0 0 20 1.3 0.00081 12 0.045 0.62
U2AF2 59976 17416 105616 3 3 3 0 0 20 0.86 0.00082 13 0.046 0.62
EBF3 68768 19432 131040 3 3 2 1 0 4 0.71 0.00087 14 0.046 0.64
GTF2I 82040 22456 221144 3 3 2 0 0 20 0.77 0.00093 12 0.045 0.65
ASCL3 23688 7000 14280 2 2 2 0 0 20 0.97 0.0012 9.9 0.042 0.79
DKK2 34552 9688 46704 3 3 2 0 0 20 1.7 0.0013 12 0.045 0.84
DFNA5 65296 19600 111104 2 2 1 0 0 20 0.73 0.0014 12 0.047 0.84
RAB40C 35392 10360 45416 2 2 1 0 1 20 1.2 0.0014 12 0.048 0.84
SRL 62384 17752 67648 2 2 2 0 0 20 0 0.0015 7.6 0.036 0.84
PLAC4 8064 2912 2576 1 1 1 0 0 20 0.9 0.0015 7.3 0.036 0.84
TRIM60 62664 16464 6888 3 3 2 0 0 20 0.78 0.0015 11 0.047 0.84
PPPDE1 26376 7224 79072 1 1 1 0 0 20 0.29 0.0016 7.3 0.034 0.87
LONP1 124432 37352 172144 5 4 5 0 0 14 0.55 0.0017 14 0.048 0.87
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. ##REF##46

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)
Copyright © 2013 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle