Mutation Analysis (MutSigCV v0.9)
Acute Myeloid Leukemia (Primary blood derived cancer - Peripheral blood)
21 August 2015  |  analyses__2015_08_21
Maintainer Information
Citation Information
doi:10.7908/C1W09569
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/C1W09569
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: LAML-TB

  • Number of patients in set: 197

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:LAML-TB.final_analysis_set.maf

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

  • Significantly mutated genes (q ≤ 0.1): 16

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: LAML-TB.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: 16. 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
CEBPA 34869 10638 788 19 13 16 0 0 20 1.3 0 90 0.12 0
DNMT3A 408184 113275 85498 56 50 28 0 0 18 0 0 180 0.12 0
IDH2 180846 47674 35263 20 20 2 0 0 20 0 0 68 0.12 0
NPM1 140855 34278 45507 35 34 8 0 0 4 0 1e-15 200 0.12 4.6e-12
FLT3 471027 122140 91408 54 54 29 0 2 8 11 2.7e-15 240 0.26 9.7e-12
TET2 542538 144598 4728 27 17 26 0 0 15 0 1.2e-14 91 0.11 3.7e-11
RUNX1 151493 47477 38415 19 16 15 0 0 13 3 1.5e-14 80 0.11 3.8e-11
NRAS 90817 24034 16154 15 15 6 0 0 20 0 4.3e-14 55 0.1 9.8e-11
IDH1 198379 51220 31914 19 19 2 0 0 13 3.4 1.6e-12 60 0.16 3.2e-09
WT1 174345 45901 40976 12 12 10 0 0 5 0 3.2e-12 64 0.11 5.9e-09
TP53 186165 54372 40582 20 16 20 0 0 4 0 1.3e-08 60 0.11 0.000021
PHF6 195030 47280 35854 6 6 6 0 0 19 1.9 8.4e-07 31 0.14 0.0013
U2AF1 124898 33884 34278 8 8 2 0 0 20 0 1.1e-06 29 0.11 0.0015
PTPN11 284665 73087 54963 9 9 9 0 0 20 1.7 6.2e-06 29 0.11 0.0081
STAG2 615625 152872 128444 6 6 6 0 0 20 0 0.000042 35 0.19 0.051
RAD21 304956 76830 51614 5 5 5 0 0 20 0 0.000054 30 0.12 0.062
KIT 464526 126080 82543 10 8 6 0 0 20 0 0.00013 29 0.11 0.14
ASXL1 683590 210002 48068 5 5 5 0 0 20 0 0.00065 29 0.11 0.66
CBFB 80376 20291 17730 2 2 2 0 0 20 0 0.0017 13 0.099 1
SMC1A 545887 137703 110123 7 7 7 0 0 20 1.7 0.0036 23 0.19 1
SUZ12 302789 75451 52993 3 3 3 0 0 20 0 0.0053 13 0.096 1
ADSS 206062 57130 49053 1 1 1 0 0 20 0.22 0.014 7.1 0.072 1
OR13H1 138885 42946 5319 2 2 2 0 0 20 2 0.016 7.5 0.077 1
OR11H12 138491 40582 4925 2 2 2 0 0 20 0 0.019 7.3 0.075 1
CALR 173557 41567 29550 2 2 2 0 0 20 2.2 0.021 13 0.11 1
SPRR4 37627 9653 4728 1 1 1 0 0 20 0 0.021 4.6 0.049 1
CD74 119185 30535 27974 2 2 2 0 0 20 0 0.023 7.3 0.084 1
LCE1B 54569 15760 4728 1 1 1 0 0 20 2.9 0.028 6.8 0.069 1
PRAMEF16 45704 13396 2167 1 1 1 0 0 20 0 0.029 4.4 0.048 1
HNRNPK 227338 63828 76042 3 2 3 0 0 15 0 0.03 12 0.099 1
PDCD2L 146962 39400 22261 2 2 2 0 0 20 1.6 0.033 7.1 0.075 1
CARD18 43734 11032 6698 1 1 1 0 0 20 0 0.04 4.5 0.053 1
PDCL3 114654 29944 22064 1 1 1 0 0 20 1.4 0.04 6.7 0.075 1
TMEM47 38218 11229 5516 1 1 1 0 0 20 1.8 0.042 4.2 0.045 1
SUMO2 41567 10047 8865 1 1 1 0 0 20 0 0.042 6.8 0.073 1
CEBPA

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

DNMT3A

Figure S2.  This figure depicts the distribution of mutations and mutation types across the DNMT3A significant gene.

IDH2

Figure S3.  This figure depicts the distribution of mutations and mutation types across the IDH2 significant gene.

NPM1

Figure S4.  This figure depicts the distribution of mutations and mutation types across the NPM1 significant gene.

FLT3

Figure S5.  This figure depicts the distribution of mutations and mutation types across the FLT3 significant gene.

TET2

Figure S6.  This figure depicts the distribution of mutations and mutation types across the TET2 significant gene.

RUNX1

Figure S7.  This figure depicts the distribution of mutations and mutation types across the RUNX1 significant gene.

NRAS

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

IDH1

Figure S9.  This figure depicts the distribution of mutations and mutation types across the IDH1 significant gene.

WT1

Figure S10.  This figure depicts the distribution of mutations and mutation types across the WT1 significant gene.

TP53

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

PHF6

Figure S12.  This figure depicts the distribution of mutations and mutation types across the PHF6 significant gene.

U2AF1

Figure S13.  This figure depicts the distribution of mutations and mutation types across the U2AF1 significant gene.

PTPN11

Figure S14.  This figure depicts the distribution of mutations and mutation types across the PTPN11 significant gene.

STAG2

Figure S15.  This figure depicts the distribution of mutations and mutation types across the STAG2 significant gene.

RAD21

Figure S16.  This figure depicts the distribution of mutations and mutation types across the RAD21 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)
Copyright © 2015 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle