Mutation Analysis (MutSigCV v0.9)
Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (Primary solid tumor)
21 August 2015  |  analyses__2015_08_21
Maintainer Information
Citation Information
doi:10.7908/C1668CCH
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/C1668CCH
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: DLBC-TP

  • Number of patients in set: 48

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:DLBC-TP.final_analysis_set.maf

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

  • Significantly mutated genes (q ≤ 0.1): 29

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: DLBC-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: 29. 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
IGLL5 13536 4176 161 41 18 34 25 0 20 2.2 7.2e-15 71 0.037 8e-11
ZNF880 18384 4560 0 34 15 10 12 0 20 1.1 9.7e-15 56 0.036 8e-11
B2M 13776 3840 448 15 13 13 0 0 20 0.73 1.3e-14 48 0.036 8e-11
TMSB4X 5424 1248 308 7 6 7 0 0 20 0.76 1.6e-09 29 0.035 7.4e-06
C11orf40 19152 5136 420 10 8 5 0 0 20 0.89 3.3e-09 36 0.036 0.000012
KRTAP4-5 19680 4992 140 14 9 9 0 0 20 1 3.1e-08 36 0.036 8e-05
MYD88 33504 8832 546 7 7 4 0 0 20 0.35 3.1e-08 34 0.035 8e-05
BTG2 13008 3792 182 20 13 17 5 0 8 1.6 1.4e-07 38 0.036 0.00032
PRAMEF1 53184 15456 448 17 13 9 8 0 20 0.59 1.7e-07 38 0.037 0.00035
HLA-DRB5 20736 6336 427 31 17 18 9 0 20 2.5 2.6e-07 36 0.036 0.00047
DMKN 50832 15360 2030 22 10 13 4 3 9 1.1 6.5e-07 42 0.037 0.0011
KLF2 6816 1872 119 5 4 5 1 0 20 1.1 5.9e-06 21 0.035 0.0084
BTG1 19248 5520 287 9 7 8 6 0 20 1.2 6e-06 26 0.036 0.0084
HLA-A 39360 11904 1078 94 13 62 41 0 20 4 7.3e-06 41 0.038 0.0095
CRIPAK 47232 15696 161 40 11 18 3 0 20 0.77 9.2e-06 30 0.036 0.011
SOCS1 6528 2016 56 9 5 9 4 0 20 1.3 9.9e-06 21 0.034 0.011
CCDC66 98688 23808 2023 14 9 7 0 0 18 0.25 0.000019 34 0.036 0.02
KRTAP10-2 28464 8352 168 19 7 8 12 0 20 0.54 2e-05 24 0.035 0.02
PIM1 34992 10272 833 41 10 32 19 6 20 2.2 0.000021 34 0.036 0.02
LCE1F 13152 3792 189 6 5 4 3 0 20 1 0.000024 21 0.035 0.021
HLA-C 39792 12240 1057 61 15 45 30 0 20 2.2 0.000024 35 0.036 0.021
KRTAP10-10 27696 8352 168 20 6 13 12 0 20 1.3 0.000026 27 0.036 0.022
FAM72B 14352 3648 406 5 5 1 1 0 20 0.32 0.000028 19 0.034 0.022
ZNF285 68688 16656 448 13 10 7 5 0 20 1.1 0.000029 34 0.036 0.022
TPRX1 19872 7248 91 13 9 7 7 0 20 1.1 0.000047 23 0.035 0.034
ZNF80 31344 7968 168 7 6 5 2 0 20 0.74 0.000063 24 0.035 0.044
NBPF15 28272 7104 567 9 8 5 0 0 20 0.75 0.000065 22 0.037 0.044
MDP1 26496 7632 1022 4 4 1 0 0 20 0.48 9e-05 21 0.036 0.059
OR13C2 35424 10176 189 18 5 6 2 0 20 1.2 0.00013 25 0.035 0.08
DHRS4 28800 9216 987 12 6 4 9 0 20 1.4 0.00019 24 0.036 0.11
CBWD6 19152 4896 798 4 4 2 2 0 20 0.81 0.0002 19 0.034 0.12
EPB41L4A 77184 20304 3073 10 7 6 4 0 20 1 0.00024 31 0.036 0.13
DEFA3 6768 1872 175 5 5 1 0 0 20 0.76 0.00025 14 0.035 0.13
OR1S2 36000 10704 189 18 14 7 11 0 20 1.9 0.00025 27 0.036 0.13
PRSS3 28128 8304 728 8 8 5 7 0 20 1.5 0.00026 24 0.037 0.13
ZNF880

Figure S1.  This figure depicts the distribution of mutations and mutation types across the ZNF880 significant gene.

B2M

Figure S2.  This figure depicts the distribution of mutations and mutation types across the B2M significant gene.

C11orf40

Figure S3.  This figure depicts the distribution of mutations and mutation types across the C11orf40 significant gene.

KRTAP4-5

Figure S4.  This figure depicts the distribution of mutations and mutation types across the KRTAP4-5 significant gene.

MYD88

Figure S5.  This figure depicts the distribution of mutations and mutation types across the MYD88 significant gene.

BTG2

Figure S6.  This figure depicts the distribution of mutations and mutation types across the BTG2 significant gene.

PRAMEF1

Figure S7.  This figure depicts the distribution of mutations and mutation types across the PRAMEF1 significant gene.

DMKN

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

KLF2

Figure S9.  This figure depicts the distribution of mutations and mutation types across the KLF2 significant gene.

BTG1

Figure S10.  This figure depicts the distribution of mutations and mutation types across the BTG1 significant gene.

HLA-A

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

CRIPAK

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

SOCS1

Figure S13.  This figure depicts the distribution of mutations and mutation types across the SOCS1 significant gene.

CCDC66

Figure S14.  This figure depicts the distribution of mutations and mutation types across the CCDC66 significant gene.

KRTAP10-2

Figure S15.  This figure depicts the distribution of mutations and mutation types across the KRTAP10-2 significant gene.

PIM1

Figure S16.  This figure depicts the distribution of mutations and mutation types across the PIM1 significant gene.

LCE1F

Figure S17.  This figure depicts the distribution of mutations and mutation types across the LCE1F significant gene.

HLA-C

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

KRTAP10-10

Figure S19.  This figure depicts the distribution of mutations and mutation types across the KRTAP10-10 significant gene.

FAM72B

Figure S20.  This figure depicts the distribution of mutations and mutation types across the FAM72B significant gene.

ZNF285

Figure S21.  This figure depicts the distribution of mutations and mutation types across the ZNF285 significant gene.

TPRX1

Figure S22.  This figure depicts the distribution of mutations and mutation types across the TPRX1 significant gene.

ZNF80

Figure S23.  This figure depicts the distribution of mutations and mutation types across the ZNF80 significant gene.

NBPF15

Figure S24.  This figure depicts the distribution of mutations and mutation types across the NBPF15 significant gene.

MDP1

Figure S25.  This figure depicts the distribution of mutations and mutation types across the MDP1 significant gene.

OR13C2

Figure S26.  This figure depicts the distribution of mutations and mutation types across the OR13C2 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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