Mutation Analysis (MutSigCV v0.9)
Pancreatic Adenocarcinoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
Maintained by David Heiman (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/C1K936FW
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: PAAD-TP

  • Number of patients in set: 91

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
  • MAF used for this analysis:PAAD-TP.final_analysis_set.maf

  • Blacklist used for this analysis: pancan_mutation_blacklist.v14.hg19.txt

  • Significantly mutated genes (q ≤ 0.1): 364

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: PAAD-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: 364. 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
CHGA 56602 15470 8280 12 12 2 1 0 20 1.6 0 66 0.093 0
ERF 100009 33670 6660 19 16 6 0 0 20 0.69 0 88 0.2 0
GAS2L2 177541 58604 9540 23 23 4 0 0 20 0.48 0 120 0.089 0
QRICH1 171808 50414 18450 15 15 2 1 0 20 1.4 0 77 0.097 0
TAOK2 302757 97643 31860 23 20 6 1 0 20 0.78 0 100 0.088 0
TMC4 138957 46592 22680 19 19 2 0 0 20 1.7 0 100 0.09 0
TMEM184A 71344 21658 9810 19 18 3 0 0 20 1.1 0 100 0.089 0
TNFSF9 26754 10192 3510 19 19 1 1 0 20 0.88 4.4e-16 120 0.09 1e-12
SRP14 32123 9373 9630 18 18 1 0 0 13 1.5 2e-15 110 0.089 3.5e-12
CCDC28B 54964 17108 11430 16 16 2 0 0 20 0.96 2.2e-15 93 0.2 3.5e-12
TP53 85995 25116 18540 59 59 48 0 0 4 0 2.4e-15 200 0.09 3.5e-12
TMEM175 96551 32214 16740 16 14 5 0 0 20 0.91 2.7e-15 74 0.09 3.5e-12
BRDT 209664 52416 31500 17 17 2 0 0 20 0.26 2.8e-15 91 0.2 3.5e-12
MED15 158249 45227 29970 28 24 5 0 0 20 0.86 2.8e-15 130 0.094 3.5e-12
CDKN2A 54782 15561 5580 22 21 14 0 0 6 1.2 3e-15 100 0.096 3.5e-12
B4GALT2 76804 24115 10260 10 10 1 0 0 20 0.33 3.1e-15 59 0.09 3.5e-12
ZMIZ1 228319 67431 37080 17 17 5 1 0 7 0.66 3.8e-15 86 0.089 3.6e-12
CIR1 94003 21840 20340 16 16 1 0 0 20 0.67 3.9e-15 92 0.096 3.6e-12
EDC4 291837 90272 50760 19 18 3 1 0 15 1.3 4e-15 89 0.094 3.6e-12
NFAT5 331058 91273 23220 21 20 4 0 0 20 2.7 4e-15 92 0.095 3.6e-12
DHX57 301210 84721 41400 23 20 4 2 0 20 0.71 4.8e-15 100 0.2 3.6e-12
FGF10 45227 12194 5670 14 14 1 0 0 8 1.6 4.8e-15 80 0.2 3.6e-12
OLIG3 41951 12467 1440 13 12 3 2 0 20 0.57 4.8e-15 70 0.092 3.6e-12
THBS4 196196 52962 35100 21 21 3 0 0 20 0.76 4.9e-15 110 0.088 3.6e-12
CXXC4 41769 12649 3960 13 13 2 0 0 20 0.54 5e-15 76 0.2 3.6e-12
SORBS2 250159 68887 32760 17 17 4 1 0 20 1 5.2e-15 84 0.088 3.7e-12
OR10A7 66248 19747 2430 30 30 2 0 0 20 0.94 6.1e-15 180 0.89 3.8e-12
MEPCE 109564 36218 6120 19 18 3 0 0 20 1.4 6.3e-15 99 0.089 3.8e-12
DDX55 136955 37037 27900 19 19 1 0 0 20 0.85 6.8e-15 110 0.2 3.8e-12
FADS2 92001 23660 19440 13 13 1 0 0 20 0.68 6.9e-15 75 0.15 3.8e-12
IFNGR2 68159 19201 10800 13 13 1 0 0 20 0.94 7e-15 76 0.096 3.8e-12
PHF13 62244 17563 6570 14 14 1 0 0 20 0.58 7e-15 85 0.088 3.8e-12
TMEM40 46592 13104 17100 16 16 2 0 0 20 0.96 7.1e-15 97 0.09 3.8e-12
SYT15 92183 28301 11970 13 13 3 0 0 10 0.8 7.4e-15 65 0.088 3.8e-12
C19orf55 55874 18655 24570 18 18 3 0 0 9 1 7.5e-15 97 0.19 3.8e-12
CHGA

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

ERF

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

GAS2L2

Figure S3.  This figure depicts the distribution of mutations and mutation types across the GAS2L2 significant gene.

QRICH1

Figure S4.  This figure depicts the distribution of mutations and mutation types across the QRICH1 significant gene.

TAOK2

Figure S5.  This figure depicts the distribution of mutations and mutation types across the TAOK2 significant gene.

TMC4

Figure S6.  This figure depicts the distribution of mutations and mutation types across the TMC4 significant gene.

TMEM184A

Figure S7.  This figure depicts the distribution of mutations and mutation types across the TMEM184A significant gene.

TNFSF9

Figure S8.  This figure depicts the distribution of mutations and mutation types across the TNFSF9 significant gene.

SRP14

Figure S9.  This figure depicts the distribution of mutations and mutation types across the SRP14 significant gene.

CCDC28B

Figure S10.  This figure depicts the distribution of mutations and mutation types across the CCDC28B significant gene.

TP53

Figure S11.  This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

TMEM175

Figure S12.  This figure depicts the distribution of mutations and mutation types across the TMEM175 significant gene.

BRDT

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

MED15

Figure S14.  This figure depicts the distribution of mutations and mutation types across the MED15 significant gene.

CDKN2A

Figure S15.  This figure depicts the distribution of mutations and mutation types across the CDKN2A significant gene.

B4GALT2

Figure S16.  This figure depicts the distribution of mutations and mutation types across the B4GALT2 significant gene.

ZMIZ1

Figure S17.  This figure depicts the distribution of mutations and mutation types across the ZMIZ1 significant gene.

CIR1

Figure S18.  This figure depicts the distribution of mutations and mutation types across the CIR1 significant gene.

EDC4

Figure S19.  This figure depicts the distribution of mutations and mutation types across the EDC4 significant gene.

NFAT5

Figure S20.  This figure depicts the distribution of mutations and mutation types across the NFAT5 significant gene.

DHX57

Figure S21.  This figure depicts the distribution of mutations and mutation types across the DHX57 significant gene.

FGF10

Figure S22.  This figure depicts the distribution of mutations and mutation types across the FGF10 significant gene.

OLIG3

Figure S23.  This figure depicts the distribution of mutations and mutation types across the OLIG3 significant gene.

THBS4

Figure S24.  This figure depicts the distribution of mutations and mutation types across the THBS4 significant gene.

CXXC4

Figure S25.  This figure depicts the distribution of mutations and mutation types across the CXXC4 significant gene.

SORBS2

Figure S26.  This figure depicts the distribution of mutations and mutation types across the SORBS2 significant gene.

OR10A7

Figure S27.  This figure depicts the distribution of mutations and mutation types across the OR10A7 significant gene.

MEPCE

Figure S28.  This figure depicts the distribution of mutations and mutation types across the MEPCE significant gene.

FADS2

Figure S29.  This figure depicts the distribution of mutations and mutation types across the FADS2 significant gene.

IFNGR2

Figure S30.  This figure depicts the distribution of mutations and mutation types across the IFNGR2 significant gene.

PHF13

Figure S31.  This figure depicts the distribution of mutations and mutation types across the PHF13 significant gene.

TMEM40

Figure S32.  This figure depicts the distribution of mutations and mutation types across the TMEM40 significant gene.

SYT15

Figure S33.  This figure depicts the distribution of mutations and mutation types across the SYT15 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

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)