Mutation Analysis (MutSigCV v0.6)
Lung Squamous Cell Carcinoma (Primary solid tumor)
22 February 2013  |  analyses__2013_02_22
Maintainer Information
Citation Information
doi:10.7908/C11V5C64
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/C11V5C64
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: LUSC-TP

  • Number of patients in set: 178

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: LUSC-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: 7. 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 168210 49128 206 147 141 98 7 0 4 3 2.7e-15 430 0.18 4.9e-11
CDKN2A 107156 30438 62 26 26 23 1 0 6 2 2.6e-14 96 0.18 2.4e-10
PTEN 173372 41652 174 16 14 15 0 0 20 0.93 1.2e-09 61 0.39 7.5e-06
KEAP1 231400 67640 87 24 22 21 0 0 20 0.55 5.7e-09 58 0.19 0.000026
NFE2L2 250802 66394 81 28 27 15 0 0 20 1.3 3.9e-07 63 0.16 0.0014
MLL2 1885198 623178 771 41 35 41 6 0 20 0.73 0.000022 110 0.17 0.059
RB1 506944 133678 486 12 12 12 0 0 20 0.61 0.000023 53 0.18 0.059
SLC17A8 252048 69420 241 15 13 15 0 0 1 0 0.000087 41 0.18 0.2
ASCL4 31328 11392 10 6 6 6 0 0 20 1 0.00011 24 0.17 0.21
FBXW7 345676 94874 239 11 11 9 3 0 20 0.54 0.00013 40 0.17 0.23
PIK3CA 462622 118370 396 29 27 16 1 0 20 0.86 0.00014 54 0.18 0.23
ELTD1 288894 77252 288 18 18 18 2 0 15 1.6 0.00049 52 0.18 0.75
MORF4L2 120328 33642 24 4 4 4 0 0 20 0.14 0.00053 17 0.15 0.75
DACH2 214846 61944 169 10 9 10 0 0 5 0 0.00092 28 0.18 1
DET1 227840 66394 74 5 5 5 0 0 11 0 0.00099 19 0.17 1
GLRA4 218762 58028 151 7 6 7 0 0 20 0.14 0.0012 20 0.16 1
LEPROT 53400 16198 64 4 4 4 0 0 15 0.93 0.002 19 0.17 1
HLA-A 145960 44144 154 7 6 7 0 0 20 0.88 0.0022 30 0.17 1
LRRC4C 262728 78676 24 19 17 19 1 0 13 1 0.0024 39 0.17 1
FAM159A 72802 21004 52 5 5 5 1 0 20 0.55 0.0024 18 0.16 1
CSMD3 1583488 442508 1422 124 81 122 21 0 5 2.8 0.0026 150 0.19 1
TDRD5 417054 116768 323 15 14 15 2 0 11 0.58 0.003 38 0.18 1
GPR174 135458 38270 24 6 5 6 1 0 19 0.69 0.0032 23 0.17 1
APOBEC1 102350 26522 103 7 7 7 1 0 20 0.74 0.0033 21 0.18 1
KIAA0831 197758 53578 181 3 3 3 0 0 6 0.19 0.0034 19 0.18 1
CYP11B1 208616 63190 428 15 15 15 0 0 3 0.45 0.0034 34 0.18 1
REG3G 76006 20648 103 8 8 8 1 0 1 1.2 0.0036 30 0.18 1
HS6ST1 106622 31506 16 5 5 5 0 0 20 0.45 0.0037 19 0.16 1
APLNR 152368 46102 24 7 7 7 0 0 20 0.73 0.0037 26 0.38 1
FAM58B 99146 30082 12 5 5 5 1 0 20 0.86 0.0037 23 0.18 1
MAGEA4 127448 39338 120 7 7 7 0 0 7 0.6 0.0037 23 0.16 1
SPRED3 57850 19224 71 4 3 4 1 0 20 0.42 0.0045 15 0.16 1
GBA3 177644 47348 654 11 9 11 1 0 6 0.73 0.0048 28 0.17 1
RASA1 413316 113386 486 8 8 8 0 0 1 0 0.0049 37 0.19 1
PDYN 105376 31150 44 11 10 11 1 0 7 0.94 0.0051 25 0.18 1
TP53

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

CDKN2A

Figure S2.  This figure depicts the distribution of mutations and mutation types across the CDKN2A significant gene.

PTEN

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

KEAP1

Figure S4.  This figure depicts the distribution of mutations and mutation types across the KEAP1 significant gene.

NFE2L2

Figure S5.  This figure depicts the distribution of mutations and mutation types across the NFE2L2 significant gene.

MLL2

Figure S6.  This figure depicts the distribution of mutations and mutation types across the MLL2 significant gene.

RB1

Figure S7.  This figure depicts the distribution of mutations and mutation types across the RB1 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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