Mutation Analysis (MutSigCV v0.9)
Lung Adenocarcinoma (Primary solid tumor)
28 January 2016  |  analyses__2016_01_28
Maintainer Information
Citation Information
Maintained by David Heiman (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2016): Mutation Analysis (MutSigCV v0.9). Broad Institute of MIT and Harvard. doi:10.7908/C13X862Q
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: LUAD-TP

  • Number of patients in set: 563

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:LUAD-TP.final_analysis_set.maf

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

  • Significantly mutated genes (q ≤ 0.1): 1498

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: LUAD-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: 1498. 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
STK11 281718 81436 38010 88 81 69 2 0 20 0.77 0 460 0.65 0
EGFR 1733844 473990 494088 87 73 38 4 1 20 0.63 1.1e-16 300 0.8 1e-12
RIMS2 1884837 529923 1038492 109 91 101 18 0 6 1.7 3.3e-16 230 0.94 2e-12
RB1 1604208 423009 424144 33 32 32 1 0 20 0.64 5.6e-16 170 0.97 2.5e-12
COL11A1 2412051 757288 964754 147 117 138 18 6 18 2.3 8.9e-16 280 0.64 3e-12
KRAS 340783 83352 82544 173 167 11 0 0 1 1.6 1e-15 420 0.83 3e-12
DST 8847710 2283105 4405492 147 103 143 26 0 0 0.56 1.4e-15 240 0.57 3.8e-12
TP53 532035 155388 144480 322 305 175 4 0 4 0.96 1.7e-15 1200 0.75 3.8e-12
SMARCA4 1826749 516632 432446 47 44 45 5 0 20 0.61 3.4e-15 170 0.63 5.5e-12
COL5A2 1878728 635823 780836 59 55 56 12 0 20 0.98 4e-15 160 0.71 5.5e-12
CSMD3 5009960 1399982 1122212 395 229 361 71 5 5 5 4.1e-15 450 0.52 5.5e-12
RBM10 867340 245471 206024 40 38 35 2 0 16 0.83 4.1e-15 210 1 5.5e-12
DCDC1 491132 133459 122262 75 65 70 22 0 20 3.1 4.2e-15 200 0.62 5.5e-12
EPHA5 1340615 372143 285656 81 69 77 16 0 13 2.1 4.2e-15 180 0.89 5.5e-12
KEAP1 732404 214108 64526 100 99 85 2 0 20 0.88 5.2e-15 350 0.67 6.3e-12
OR8U1 407640 114880 17136 39 36 39 2 0 20 0.85 6.2e-15 110 1.3 7.1e-12
NF1 5300412 1485502 954940 73 64 67 7 0 0 0.41 1e-14 240 0.69 1.1e-11
BRAF 972441 277615 281162 47 43 22 1 0 19 0.88 1.1e-14 140 0.74 1.1e-11
ZCCHC5 566496 161301 10752 31 28 30 8 0 11 0.66 1.8e-14 93 1.4 1.7e-11
OVCH1 1366687 380364 305438 59 48 56 13 0 20 1.3 4.8e-14 140 0.93 4.4e-11
FLG 5174048 1535665 36036 215 136 206 46 0 15 1.5 8.1e-14 260 0.5 7e-11
GPR112 3971287 1261823 368634 115 97 109 37 0 20 1.4 2.7e-13 210 0.63 2.3e-10
SNTG1 702145 193109 265594 70 64 65 15 0 9 4.2 6.8e-13 160 0.9 5.4e-10
LTBP1 2177376 579778 546294 63 57 60 13 0 20 1.1 1.6e-12 150 0.53 1.2e-09
TMTC1 1029080 291015 273308 58 50 54 9 2 18 1.9 2.3e-12 140 1.1 1.7e-09
ABCB5 1624762 462758 368690 60 55 60 19 2 20 1.4 2.9e-12 150 1 2e-09
HRNR 2664412 881935 35266 92 74 89 23 0 20 1.2 3.3e-12 170 0.74 2.2e-09
SMAD4 745524 207775 168980 22 22 21 3 3 20 0.7 3.6e-12 89 0.57 2.3e-09
ZNF804A 1616569 426810 61572 110 92 105 17 0 3 3.3 4.4e-12 210 1.2 2.8e-09
LRP1B 6310568 1575974 1419712 349 202 332 63 1 6 3.8 5.2e-12 390 0.8 3.2e-09
EPHA6 1401220 391425 268772 63 58 58 9 0 5 1.5 6.9e-12 160 0.67 4.1e-09
ATM 4202969 1080173 917126 55 46 53 2 0 2 0.31 1.5e-11 160 0.57 8.8e-09
TAF1L 2416029 663833 16744 71 61 65 12 0 20 1.2 2.2e-11 150 0.95 1.2e-08
COL19A1 1512526 465657 776748 59 50 58 10 0 9 1.6 4.1e-11 150 0.69 2.2e-08
ARID1A 2515033 740936 295092 39 35 37 3 0 2 0.58 4.1e-11 150 0.63 2.2e-08
STK11

Figure S1.  This figure depicts the distribution of mutations and mutation types across the STK11 significant gene.

EGFR

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

RIMS2

Figure S3.  This figure depicts the distribution of mutations and mutation types across the RIMS2 significant gene.

RB1

Figure S4.  This figure depicts the distribution of mutations and mutation types across the RB1 significant gene.

COL11A1

Figure S5.  This figure depicts the distribution of mutations and mutation types across the COL11A1 significant gene.

KRAS

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

TP53

Figure S7.  This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

SMARCA4

Figure S8.  This figure depicts the distribution of mutations and mutation types across the SMARCA4 significant gene.

COL5A2

Figure S9.  This figure depicts the distribution of mutations and mutation types across the COL5A2 significant gene.

CSMD3

Figure S10.  This figure depicts the distribution of mutations and mutation types across the CSMD3 significant gene.

RBM10

Figure S11.  This figure depicts the distribution of mutations and mutation types across the RBM10 significant gene.

DCDC1

Figure S12.  This figure depicts the distribution of mutations and mutation types across the DCDC1 significant gene.

EPHA5

Figure S13.  This figure depicts the distribution of mutations and mutation types across the EPHA5 significant gene.

KEAP1

Figure S14.  This figure depicts the distribution of mutations and mutation types across the KEAP1 significant gene.

OR8U1

Figure S15.  This figure depicts the distribution of mutations and mutation types across the OR8U1 significant gene.

NF1

Figure S16.  This figure depicts the distribution of mutations and mutation types across the NF1 significant gene.

BRAF

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

ZCCHC5

Figure S18.  This figure depicts the distribution of mutations and mutation types across the ZCCHC5 significant gene.

OVCH1

Figure S19.  This figure depicts the distribution of mutations and mutation types across the OVCH1 significant gene.

FLG

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

GPR112

Figure S21.  This figure depicts the distribution of mutations and mutation types across the GPR112 significant gene.

SNTG1

Figure S22.  This figure depicts the distribution of mutations and mutation types across the SNTG1 significant gene.

LTBP1

Figure S23.  This figure depicts the distribution of mutations and mutation types across the LTBP1 significant gene.

TMTC1

Figure S24.  This figure depicts the distribution of mutations and mutation types across the TMTC1 significant gene.

ABCB5

Figure S25.  This figure depicts the distribution of mutations and mutation types across the ABCB5 significant gene.

HRNR

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

SMAD4

Figure S27.  This figure depicts the distribution of mutations and mutation types across the SMAD4 significant gene.

ZNF804A

Figure S28.  This figure depicts the distribution of mutations and mutation types across the ZNF804A significant gene.

LRP1B

Figure S29.  This figure depicts the distribution of mutations and mutation types across the LRP1B significant gene.

EPHA6

Figure S30.  This figure depicts the distribution of mutations and mutation types across the EPHA6 significant gene.

ATM

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

TAF1L

Figure S32.  This figure depicts the distribution of mutations and mutation types across the TAF1L significant gene.

COL19A1

Figure S33.  This figure depicts the distribution of mutations and mutation types across the COL19A1 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)