Mutation Analysis (MutSigCV v0.9)
Lung Adenocarcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C1X929CZ
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/C1X929CZ
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): 1452

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: 1452. 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
KEAP1 732368 214096 54349 100 99 85 2 0 20 0.89 0 350 0.8 0
C1orf173 1983172 552918 174823 106 88 101 24 0 4 1.6 7.8e-16 210 0.47 6.3e-12
KRAS 340771 83350 69864 173 167 11 0 0 1 1.6 1.4e-15 420 0.39 6.3e-12
TP53 532035 155388 120976 322 305 175 4 0 4 1 1.8e-15 1200 0.42 6.3e-12
BRAF 972431 277611 239383 47 43 22 1 0 19 0.92 2.3e-15 140 0.43 6.3e-12
EGFR 1733858 473994 421164 88 74 39 4 0 20 0.61 2.7e-15 310 0.44 6.3e-12
STK11 281622 81410 32287 88 81 69 2 0 20 0.7 2.7e-15 460 0.73 6.3e-12
LPPR4 905867 266299 85817 69 61 64 7 0 20 2.1 2.8e-15 150 0.56 6.3e-12
RBM10 867478 245511 171852 40 38 35 2 0 16 0.79 4.4e-15 210 0.73 8.5e-12
COL11A1 2411919 757244 814499 153 122 143 18 0 18 2.2 4.7e-15 290 0.47 8.5e-12
SMARCA4 1826521 516566 366293 47 44 45 5 0 20 0.65 5.7e-15 170 1.1 9e-12
DCDC1 491118 133457 103865 75 65 70 22 0 20 3.2 6.7e-15 200 0.4 9e-12
RIMS2 1884803 529913 866266 109 91 101 18 0 6 1.9 6.9e-15 220 0.55 9e-12
NF1 5300308 1485480 810954 73 64 67 7 0 0 0.43 7.2e-15 230 0.61 9e-12
RB1 1604152 422995 362744 33 32 32 1 0 20 0.62 7.8e-15 170 0.72 9e-12
CSMD3 5009852 1399956 951046 400 233 365 71 0 5 4.9 7.9e-15 470 0.45 9e-12
DST 8847658 2283095 3615806 149 105 145 26 0 0 0.63 8.5e-15 240 0.45 9.2e-12
OR8U1 407638 114878 14376 39 36 39 2 0 20 0.78 9.8e-15 110 0.75 9.9e-12
C6orf25 353053 85576 74251 12 12 2 0 0 20 0.31 4.9e-14 74 0.45 4.7e-11
EPHA5 1340607 372143 243620 81 69 77 16 0 13 2.2 5.8e-14 170 0.44 5.3e-11
SMAD4 745516 207773 142702 24 23 23 4 0 20 0.55 6.2e-14 93 0.85 5.4e-11
COL5A2 1878688 635809 660422 59 55 56 12 0 20 1.1 8e-14 150 0.46 6.6e-11
FLG 5173962 1535639 30646 215 136 206 46 0 15 1.4 9.5e-14 260 0.45 7.5e-11
LRP1B 6310374 1575924 1204768 349 202 332 63 0 6 3.5 1.7e-13 390 0.47 1.3e-10
ZCCHC5 566568 161321 8832 31 28 30 8 0 11 0.67 2.1e-13 90 0.57 1.5e-10
ABCB5 1624766 462760 311955 62 57 62 19 0 20 1.5 4.1e-13 150 0.4 2.9e-10
OVCH1 1366747 380380 258725 59 48 56 13 0 20 1.3 5e-13 140 0.86 3.4e-10
TMTC1 1029086 291019 232538 60 52 56 9 0 18 2 6.5e-13 140 0.42 4.3e-10
PLCB1 1713642 444155 493820 60 55 55 12 0 11 1.1 9.4e-13 150 0.83 5.9e-10
SNTG1 702139 193109 225439 70 64 65 15 0 9 4.2 2.2e-12 160 0.88 1.3e-09
LTBP1 2177398 579786 464841 63 57 60 13 0 20 1.1 2.5e-12 150 0.67 1.5e-09
GPR112 3971255 1261813 313311 115 97 109 37 0 20 1.5 3.7e-12 210 0.46 2.1e-09
ATM 4203037 1080189 772705 55 46 53 2 0 2 0.27 1.2e-11 160 0.42 6.7e-09
SGIP1 1108807 336163 435854 44 40 41 6 0 20 1.1 1.4e-11 110 0.7 7.5e-09
HRNR 2664230 881875 29995 92 74 89 23 0 20 1.2 2.1e-11 170 0.61 1.1e-08
KEAP1

Figure S1.  This figure depicts the distribution of mutations and mutation types across the KEAP1 significant gene.

C1orf173

Figure S2.  This figure depicts the distribution of mutations and mutation types across the C1orf173 significant gene.

KRAS

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

TP53

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

BRAF

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

EGFR

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

STK11

Figure S7.  This figure depicts the distribution of mutations and mutation types across the STK11 significant gene.

LPPR4

Figure S8.  This figure depicts the distribution of mutations and mutation types across the LPPR4 significant gene.

RBM10

Figure S9.  This figure depicts the distribution of mutations and mutation types across the RBM10 significant gene.

COL11A1

Figure S10.  This figure depicts the distribution of mutations and mutation types across the COL11A1 significant gene.

SMARCA4

Figure S11.  This figure depicts the distribution of mutations and mutation types across the SMARCA4 significant gene.

DCDC1

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

RIMS2

Figure S13.  This figure depicts the distribution of mutations and mutation types across the RIMS2 significant gene.

NF1

Figure S14.  This figure depicts the distribution of mutations and mutation types across the NF1 significant gene.

RB1

Figure S15.  This figure depicts the distribution of mutations and mutation types across the RB1 significant gene.

CSMD3

Figure S16.  This figure depicts the distribution of mutations and mutation types across the CSMD3 significant gene.

C6orf25

Figure S17.  This figure depicts the distribution of mutations and mutation types across the C6orf25 significant gene.

EPHA5

Figure S18.  This figure depicts the distribution of mutations and mutation types across the EPHA5 significant gene.

SMAD4

Figure S19.  This figure depicts the distribution of mutations and mutation types across the SMAD4 significant gene.

COL5A2

Figure S20.  This figure depicts the distribution of mutations and mutation types across the COL5A2 significant gene.

FLG

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

LRP1B

Figure S22.  This figure depicts the distribution of mutations and mutation types across the LRP1B significant gene.

ZCCHC5

Figure S23.  This figure depicts the distribution of mutations and mutation types across the ZCCHC5 significant gene.

ABCB5

Figure S24.  This figure depicts the distribution of mutations and mutation types across the ABCB5 significant gene.

OVCH1

Figure S25.  This figure depicts the distribution of mutations and mutation types across the OVCH1 significant gene.

TMTC1

Figure S26.  This figure depicts the distribution of mutations and mutation types across the TMTC1 significant gene.

PLCB1

Figure S27.  This figure depicts the distribution of mutations and mutation types across the PLCB1 significant gene.

SNTG1

Figure S28.  This figure depicts the distribution of mutations and mutation types across the SNTG1 significant gene.

LTBP1

Figure S29.  This figure depicts the distribution of mutations and mutation types across the LTBP1 significant gene.

GPR112

Figure S30.  This figure depicts the distribution of mutations and mutation types across the GPR112 significant gene.

ATM

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

SGIP1

Figure S32.  This figure depicts the distribution of mutations and mutation types across the SGIP1 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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