Mutation Analysis (MutSigCV v0.9)
Bladder Urothelial Carcinoma (Primary solid tumor)
15 January 2014  |  analyses__2014_01_15
Maintainer Information
Citation Information
doi:10.7908/C1DF6PMW
Maintained by Dan DiCara (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Mutation Analysis (MutSigCV v0.9). Broad Institute of MIT and Harvard. doi:10.7908/C1DF6PMW
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: BLCA-TP

  • Number of patients in set: 28

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). If the figure is unpopulated, then full coverage is assumed (e.g. MutSig CV doesn't use WIGs and assumes full coverage).

Figure 1. 

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

Figure 2.  Patients counts and rates file used to generate this plot: BLCA-TP.patients.counts_and_rates.txt

Lego Plots

The mutation spectrum is depicted in the lego plots below in which the 96 possible mutation types are subdivided into six large blocks, color-coded to reflect the base substitution type. Each large block is further subdivided into the 16 possible pairs of 5' and 3' neighbors, as listed in the 4x4 trinucleotide context legend. The height of each block corresponds to the mutation frequency for that kind of mutation (counts of mutations normalized by the base coverage in a given bin). The shape of the spectrum is a signature for dominant mutational mechanisms in different tumor types.

Figure 3.  Get High-res Image SNV Mutation rate lego plot for entire set. Each bin is normalized by base coverage for that bin. Colors represent the six SNV types on the upper right. The three-base context for each mutation is labeled in the 4x4 legend on the lower right. The fractional breakdown of SNV counts is shown in the pie chart on the upper left. If this figure is blank, not enough information was provided in the MAF to generate it.

Figure 4.  Get High-res Image SNV Mutation rate lego plots for 4 slices of mutation allele fraction (0<=AF<0.1, 0.1<=AF<0.25, 0.25<=AF<0.5, & 0.5<=AF) . The color code and three-base context legends are the same as the previous figure. If this figure is blank, not enough information was provided in the MAF to generate it.

CoMut Plot

Figure 5.  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: 0. 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 26460 7728 824 14 11 13 1 0 4 2.9 0.0023 26 0.016 1
RFTN2 31528 8484 652 3 3 3 0 0 20 1.2 0.0051 13 0.014 1
FBXW7 54376 14924 956 6 5 5 0 0 20 0 0.0058 14 0.014 1
GPS2 24836 7196 816 4 3 4 0 0 20 2.4 0.0061 12 0.014 1
ELF3 24892 6832 632 3 3 3 0 0 20 2.4 0.0075 13 0.014 1
HLA-A 22960 6944 616 3 3 3 0 0 20 0.69 0.0076 13 0.014 1
CAMKK2 33684 9268 1720 2 2 2 0 0 18 0 0.0098 11 0.014 1
KLF5 24304 7056 244 2 2 2 1 0 20 0.54 0.01 11 0.014 1
CTF1 2688 756 80 1 1 1 0 0 20 1.3 0.011 6.3 0.01 1
PYGO1 27580 7868 256 3 3 3 0 0 20 1.4 0.016 10 0.014 1
XPR1 46508 12880 1176 5 4 5 1 0 20 1.1 0.017 14 0.014 1
FEZ2 18116 4536 396 2 2 2 0 0 20 0.53 0.018 8.1 0.012 1
ZNF263 44716 12600 476 3 3 3 0 0 20 0.93 0.019 12 0.014 1
LASP1 15008 3780 472 2 2 2 0 0 20 0.8 0.025 7.9 0.012 1
C11orf85 15064 3864 632 2 2 2 0 0 20 0.6 0.029 7.9 0.012 1
NUDT14 10836 3528 268 1 1 1 0 0 20 0.58 0.03 5.7 0.011 1
LCE1F 7672 2212 108 1 1 1 0 0 20 0.82 0.033 5.9 0.01 1
GABRB2 33180 9296 740 2 2 2 1 0 20 0.37 0.034 7.8 0.013 1
ADSS 29288 8120 996 1 1 1 0 0 20 0.14 0.035 3.4 0.0058 1
FIGN 48888 14924 176 2 2 2 0 0 20 0.81 0.036 10 0.014 1
GINS1 13496 3556 564 1 1 1 0 0 19 1 0.036 5.7 0.011 1
AGFG2 26236 8680 860 2 2 2 0 0 20 2.5 0.039 10 0.014 1
MGP 6888 1792 304 1 1 1 0 0 20 0 0.042 5.9 0.01 1
OR11H12 19684 5768 100 1 1 1 0 0 20 0.77 0.042 5.6 0.01 1
TP53I13 17248 6132 356 1 1 1 0 0 20 0.82 0.042 5.7 0.011 1
TNFSF4 12236 3388 348 1 1 1 0 0 20 1.1 0.043 5.7 0.01 1
NME4 9268 2772 288 1 1 1 0 0 20 0.65 0.045 5.7 0.011 1
OR13G1 19908 5880 96 1 1 1 0 0 20 0.75 0.046 5.6 0.011 1
DDTL 4284 1232 176 1 1 1 0 0 20 0.92 0.047 3.2 0.0057 1
TRAPPC6B 10808 2688 460 1 1 1 0 0 20 0.57 0.048 5.7 0.01 1
NFE2L2 39452 10444 324 4 4 4 0 0 20 0 0.048 8.9 0.013 1
PPBP 8512 2520 256 2 2 2 0 0 20 0.51 0.051 5.6 0.01 1
C5orf58 5796 1484 164 1 1 1 0 0 20 0.56 0.052 3.1 0.0057 1
C22orf24 5600 1540 116 1 1 1 0 0 20 0.98 0.054 3.1 0.0058 1
MTX3 15232 4452 360 1 1 1 0 0 20 0 0.059 3.3 0.006 1
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

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

References
[1] TCGA, Integrated genomic analyses of ovarian carcinoma, Nature 474:609 - 615 (2011)
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