Mutation Analysis (MutSigCV v0.9)
Pancreatic Adenocarcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C1TM796S
Maintained by David Heiman (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Mutation Analysis (MutSigCV v0.9). Broad Institute of MIT and Harvard. doi:10.7908/C1TM796S
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: 146

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): 35

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: 35. 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
JMY 247762 68474 5735 56 55 3 0 0 20 1.1 0 310 0.16 0
KRAS 88330 21608 3286 127 123 5 1 0 1 1.9 0 260 0.16 0
RBM47 182792 55918 2232 27 25 3 2 0 20 0.57 0 150 0.18 0
TP53 137970 40296 6386 100 100 72 0 0 4 0 0 330 0.16 0
RIOK1 189654 44822 9238 55 55 2 0 0 15 0.63 3.2e-15 310 0.15 9.1e-12
CDKN2A 87892 24966 1922 31 30 19 1 0 6 1.4 3.4e-15 140 0.17 9.1e-12
LCE2A 36500 10366 744 46 46 1 0 0 20 0.55 3.8e-15 300 0.16 9.1e-12
SMAD4 193304 53874 6882 32 32 29 0 0 20 0.78 4e-15 140 0.16 9.1e-12
RFX1 213014 67160 7936 24 24 3 2 0 20 1.3 4.9e-15 130 0.18 9.9e-12
C1QB 84242 26718 1302 35 35 2 0 0 20 1.4 6.7e-15 210 0.17 1.2e-11
TYRO3 281196 86870 10323 14 14 5 0 0 20 1 1e-14 80 0.17 1.7e-11
GPR6 110668 41610 744 12 12 3 0 0 20 0.89 1.8e-14 69 0.17 2.8e-11
NCOA3 500488 135196 12803 17 14 7 1 0 20 0.79 9.6e-12 72 0.2 1.3e-08
FNDC1 464864 147606 9145 19 14 7 3 0 16 0.96 1.7e-10 69 0.2 2.2e-07
ZMIZ2 296818 96068 10664 12 12 4 1 0 20 1 1.9e-09 57 0.16 2.3e-06
AEBP1 362956 105412 10912 30 26 5 1 0 0 1.2 5.2e-09 120 0.16 5.9e-06
CASQ2 144686 34748 6758 8 8 2 0 0 20 1.3 1.7e-08 43 0.16 0.000019
LZTS1 188778 56502 1612 10 10 3 2 0 20 1.7 7.7e-08 49 0.16 0.000079
RPL22 44092 10658 1736 6 5 2 0 0 20 1.6 1.2e-07 31 0.15 0.00011
KCNE1 43654 13140 744 4 4 2 0 0 20 0.31 3.7e-07 25 0.16 0.00033
SHROOM4 458002 129940 4836 13 11 5 3 0 20 1.9 1.4e-06 52 0.16 0.0012
ESPN 139284 43362 4216 6 6 1 0 0 19 0.63 1.8e-06 36 0.17 0.0015
TMEM91 77234 23214 2883 6 6 2 0 0 15 1.1 2.4e-06 32 0.15 0.0019
ZNF880 55918 13870 0 6 4 2 1 0 20 1.3 6.8e-06 25 0.15 0.0052
CBX3 67744 15768 3782 4 4 1 1 0 20 1.2 8.1e-06 25 0.15 0.0059
UBAC1 132568 37814 5518 5 5 1 0 0 20 0.68 0.000026 30 0.15 0.018
RBMX 144248 30514 7812 5 5 1 0 0 20 0.44 0.000027 30 0.15 0.018
ATP2C1 388798 105412 17856 11 8 8 0 0 20 0.9 0.000029 37 0.17 0.019
TGFBR2 198560 53290 7440 10 8 10 0 0 20 0.98 0.000029 33 0.16 0.019
TGFBR1 164396 45406 4867 8 8 8 0 0 20 0.58 0.000046 28 0.16 0.028
HSPE1 34602 10366 2077 4 4 2 0 0 20 1.7 0.000048 20 0.16 0.028
RNF43 243090 76942 5425 10 9 10 1 0 8 1.9 0.000062 36 0.18 0.035
ZNF678 176076 40588 4030 5 5 3 0 0 19 0.4 0.000077 25 0.15 0.042
PRKRA 106726 28762 4216 4 4 2 0 0 20 0.68 0.00014 22 0.15 0.073
IRS4 409530 131254 744 16 16 5 3 0 1 1.7 0.00016 71 0.17 0.083
JMY

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

KRAS

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

RBM47

Figure S3.  This figure depicts the distribution of mutations and mutation types across the RBM47 significant gene.

TP53

Figure S4.  This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

RIOK1

Figure S5.  This figure depicts the distribution of mutations and mutation types across the RIOK1 significant gene.

CDKN2A

Figure S6.  This figure depicts the distribution of mutations and mutation types across the CDKN2A significant gene.

LCE2A

Figure S7.  This figure depicts the distribution of mutations and mutation types across the LCE2A significant gene.

SMAD4

Figure S8.  This figure depicts the distribution of mutations and mutation types across the SMAD4 significant gene.

RFX1

Figure S9.  This figure depicts the distribution of mutations and mutation types across the RFX1 significant gene.

C1QB

Figure S10.  This figure depicts the distribution of mutations and mutation types across the C1QB significant gene.

TYRO3

Figure S11.  This figure depicts the distribution of mutations and mutation types across the TYRO3 significant gene.

GPR6

Figure S12.  This figure depicts the distribution of mutations and mutation types across the GPR6 significant gene.

NCOA3

Figure S13.  This figure depicts the distribution of mutations and mutation types across the NCOA3 significant gene.

FNDC1

Figure S14.  This figure depicts the distribution of mutations and mutation types across the FNDC1 significant gene.

ZMIZ2

Figure S15.  This figure depicts the distribution of mutations and mutation types across the ZMIZ2 significant gene.

AEBP1

Figure S16.  This figure depicts the distribution of mutations and mutation types across the AEBP1 significant gene.

CASQ2

Figure S17.  This figure depicts the distribution of mutations and mutation types across the CASQ2 significant gene.

LZTS1

Figure S18.  This figure depicts the distribution of mutations and mutation types across the LZTS1 significant gene.

KCNE1

Figure S19.  This figure depicts the distribution of mutations and mutation types across the KCNE1 significant gene.

SHROOM4

Figure S20.  This figure depicts the distribution of mutations and mutation types across the SHROOM4 significant gene.

ESPN

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

ZNF880

Figure S22.  This figure depicts the distribution of mutations and mutation types across the ZNF880 significant gene.

CBX3

Figure S23.  This figure depicts the distribution of mutations and mutation types across the CBX3 significant gene.

UBAC1

Figure S24.  This figure depicts the distribution of mutations and mutation types across the UBAC1 significant gene.

ATP2C1

Figure S25.  This figure depicts the distribution of mutations and mutation types across the ATP2C1 significant gene.

TGFBR2

Figure S26.  This figure depicts the distribution of mutations and mutation types across the TGFBR2 significant gene.

TGFBR1

Figure S27.  This figure depicts the distribution of mutations and mutation types across the TGFBR1 significant gene.

RNF43

Figure S28.  This figure depicts the distribution of mutations and mutation types across the RNF43 significant gene.

PRKRA

Figure S29.  This figure depicts the distribution of mutations and mutation types across the PRKRA 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)
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