Mutation Analysis (MutSigCV v0.9)
Pancreatic Adenocarcinoma (Primary solid tumor)
15 January 2014 | analyses__2014_01_15
Maintainer Information
Citation Information
doi:10.7908/C1CR5RTT
Maintained by Dan DiCara (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Mutation Analysis (MutSigCV v0.9). Broad Institute of MIT and Harvard. doi:10.7908/C1CR5RTT
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: 57

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

- Significantly mutated genes (q ≤ 0.1): 64

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: 64. 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
--- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | ---
TP53 | 53865 | 15732 | 3708 | 37 | 37 | 33 | 0 | 0 | 4 | 0 | 3.3e-15 | 110 | 0.033 | 6.1e-11
TMEM40 | 29184 | 8208 | 3420 | 9 | 9 | 2 | 0 | 0 | 20 | 0.99 | 8.4e-15 | 53 | 0.032 | 7.7e-11
OR10A7 | 41496 | 12369 | 486 | 9 | 9 | 1 | 0 | 0 | 20 | 1 | 2.9e-14 | 51 | 0.032 | 1.7e-10
CDKN2A | 34314 | 9747 | 1116 | 13 | 13 | 11 | 0 | 0 | 6 | 0.73 | 2.8e-13 | 63 | 0.033 | 1.3e-09
C14orf49 | 121809 | 36480 | 5616 | 9 | 9 | 1 | 1 | 0 | 20 | 0.68 | 3.4e-11 | 49 | 0.033 | 1.2e-07
SEH1L | 57456 | 16017 | 3942 | 8 | 8 | 2 | 0 | 0 | 20 | 0.82 | 9.1e-11 | 43 | 0.033 | 2.5e-07
SRP14 | 20121 | 5871 | 1926 | 7 | 7 | 1 | 0 | 0 | 13 | 1.7 | 9.4e-11 | 40 | 0.032 | 2.5e-07
SCD | 48678 | 13794 | 2214 | 8 | 8 | 2 | 0 | 0 | 20 | 1 | 1.5e-10 | 43 | 0.032 | 3.5e-07
CXXC4 | 26163 | 7923 | 792 | 6 | 6 | 1 | 0 | 0 | 20 | 0.71 | 3.4e-10 | 36 | 0.031 | 6.9e-07
MED15 | 99123 | 28329 | 5994 | 11 | 9 | 5 | 0 | 0 | 20 | 0.72 | 6e-10 | 45 | 0.032 | 1.1e-06
TNFSF9 | 16758 | 6384 | 702 | 6 | 6 | 1 | 1 | 0 | 20 | 1.2 | 7.2e-10 | 35 | 0.032 | 1.2e-06
SMAD4 | 75468 | 21033 | 3996 | 10 | 10 | 9 | 0 | 0 | 20 | 0.59 | 1.9e-09 | 42 | 0.032 | 2.9e-06
TNFRSF9 | 35226 | 9747 | 2556 | 7 | 6 | 4 | 0 | 0 | 20 | 0.64 | 2.1e-09 | 35 | 0.032 | 3e-06
TMC4 | 87039 | 29184 | 4536 | 9 | 9 | 2 | 0 | 0 | 20 | 1.6 | 5.9e-09 | 44 | 0.033 | 7.7e-06
OR10A2 | 39501 | 12369 | 432 | 6 | 6 | 1 | 0 | 0 | 19 | 1.1 | 1.9e-08 | 34 | 0.032 | 0.000023
ST6GALNAC5 | 40812 | 11172 | 1674 | 6 | 6 | 1 | 0 | 0 | 20 | 0.95 | 2.4e-08 | 34 | 0.033 | 0.000028
EGR1 | 67716 | 22002 | 594 | 9 | 8 | 7 | 0 | 0 | 20 | 0.3 | 3.7e-08 | 35 | 0.032 | 0.000039
POP5 | 22287 | 6327 | 1764 | 5 | 5 | 1 | 0 | 0 | 20 | 0.81 | 4e-08 | 30 | 0.031 | 4e-05
KRAS | 34485 | 8436 | 1908 | 33 | 33 | 4 | 0 | 0 | 1 | 0 | 5.4e-08 | 59 | 0.033 | 5e-05
C15orf24 | 44688 | 13110 | 1836 | 6 | 6 | 1 | 0 | 0 | 20 | 0.85 | 5.5e-08 | 34 | 0.032 | 5e-05
PCDHAC2 | 123063 | 39159 | 1116 | 28 | 9 | 27 | 11 | 0 | 20 | 0.79 | 1.2e-07 | 32 | 0.032 | 0.0001
BRDT | 131328 | 32832 | 6300 | 8 | 8 | 2 | 0 | 0 | 20 | 0.34 | 1.5e-07 | 38 | 0.032 | 0.00012
TULP1 | 58140 | 16815 | 3924 | 6 | 6 | 2 | 1 | 0 | 20 | 0.54 | 2e-07 | 31 | 0.032 | 0.00016
MEPCE | 68628 | 22686 | 1224 | 8 | 7 | 3 | 0 | 0 | 20 | 1.5 | 3.3e-07 | 36 | 0.032 | 0.00025
FGF10 | 28329 | 7638 | 1134 | 6 | 6 | 1 | 0 | 0 | 8 | 1.9 | 5.1e-07 | 33 | 0.032 | 0.00037
OLIG3 | 26277 | 7809 | 288 | 6 | 5 | 3 | 2 | 0 | 20 | 0.92 | 9.3e-07 | 25 | 0.032 | 0.00065
PRDM8 | 48450 | 13965 | 1026 | 6 | 6 | 2 | 0 | 0 | 20 | 1 | 1e-06 | 29 | 0.032 | 0.00069
MBD3 | 33288 | 9291 | 1530 | 6 | 6 | 2 | 0 | 0 | 18 | 1.8 | 2e-06 | 29 | 0.032 | 0.0013
OTUD4 | 138624 | 38703 | 6516 | 8 | 7 | 3 | 0 | 0 | 17 | 0.16 | 2.4e-06 | 33 | 0.033 | 0.0015
PPARGC1B | 121182 | 36252 | 4032 | 8 | 7 | 3 | 1 | 0 | 20 | 1.1 | 2.5e-06 | 33 | 0.032 | 0.0015
FOXP2 | 101004 | 26847 | 5760 | 8 | 8 | 4 | 2 | 0 | 3 | 1.2 | 2.6e-06 | 40 | 0.032 | 0.0015
CCR3 | 46968 | 14421 | 216 | 6 | 5 | 2 | 0 | 0 | 20 | 1 | 3.1e-06 | 28 | 0.031 | 0.0018
ERF | 62643 | 21090 | 1332 | 9 | 6 | 5 | 0 | 0 | 20 | 0.9 | 6.4e-06 | 29 | 0.032 | 0.0036
PHF13 | 38988 | 11001 | 1314 | 4 | 4 | 1 | 0 | 0 | 20 | 0.63 | 8.2e-06 | 23 | 0.031 | 0.0044
BHLHB9 | 73017 | 20463 | 432 | 5 | 5 | 2 | 0 | 0 | 20 | 0.81 | 0.000012 | 26 | 0.032 | 0.0065

TP53

Figure S1. This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

TMEM40

Figure S2. This figure depicts the distribution of mutations and mutation types across the TMEM40 significant gene.

OR10A7

Figure S3. This figure depicts the distribution of mutations and mutation types across the OR10A7 significant gene.

CDKN2A

Figure S4. This figure depicts the distribution of mutations and mutation types across the CDKN2A significant gene.

C14orf49

Figure S5. This figure depicts the distribution of mutations and mutation types across the C14orf49 significant gene.

SEH1L

Figure S6. This figure depicts the distribution of mutations and mutation types across the SEH1L significant gene.

SRP14

Figure S7. This figure depicts the distribution of mutations and mutation types across the SRP14 significant gene.

SCD

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

MED15

Figure S9. This figure depicts the distribution of mutations and mutation types across the MED15 significant gene.

TNFSF9

Figure S10. This figure depicts the distribution of mutations and mutation types across the TNFSF9 significant gene.

SMAD4

Figure S11. This figure depicts the distribution of mutations and mutation types across the SMAD4 significant gene.

TNFRSF9

Figure S12. This figure depicts the distribution of mutations and mutation types across the TNFRSF9 significant gene.

TMC4

Figure S13. This figure depicts the distribution of mutations and mutation types across the TMC4 significant gene.

OR10A2

Figure S14. This figure depicts the distribution of mutations and mutation types across the OR10A2 significant gene.

ST6GALNAC5

Figure S15. This figure depicts the distribution of mutations and mutation types across the ST6GALNAC5 significant gene.

EGR1

Figure S16. This figure depicts the distribution of mutations and mutation types across the EGR1 significant gene.

POP5

Figure S17. This figure depicts the distribution of mutations and mutation types across the POP5 significant gene.

KRAS

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

C15orf24

Figure S19. This figure depicts the distribution of mutations and mutation types across the C15orf24 significant gene.

PCDHAC2

Figure S20. This figure depicts the distribution of mutations and mutation types across the PCDHAC2 significant gene.

BRDT

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

TULP1

Figure S22. This figure depicts the distribution of mutations and mutation types across the TULP1 significant gene.

MEPCE

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

FGF10

Figure S24. This figure depicts the distribution of mutations and mutation types across the FGF10 significant gene.

OLIG3

Figure S25. This figure depicts the distribution of mutations and mutation types across the OLIG3 significant gene.

PRDM8

Figure S26. This figure depicts the distribution of mutations and mutation types across the PRDM8 significant gene.

MBD3

Figure S27. This figure depicts the distribution of mutations and mutation types across the MBD3 significant gene.

OTUD4

Figure S28. This figure depicts the distribution of mutations and mutation types across the OTUD4 significant gene.

PPARGC1B

Figure S29. This figure depicts the distribution of mutations and mutation types across the PPARGC1B significant gene.

FOXP2

Figure S30. This figure depicts the distribution of mutations and mutation types across the FOXP2 significant gene.

CCR3

Figure S31. This figure depicts the distribution of mutations and mutation types across the CCR3 significant gene.

ERF

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

PHF13

Figure S33. This figure depicts the distribution of mutations and mutation types across the PHF13 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.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

References
[1] TCGA, Integrated genomic analyses of ovarian carcinoma, Nature 474:609 - 615 (2011)
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