Brain Lower Grade Glioma: Mutation Analysis (MutSigCV v0.9)
(primary solid tumor cohort)
Maintained by Dan DiCara (Broad Institute)
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: LGG-TP

  • Number of patients in set: 170

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
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).

Figure 1. 

Distribution of Mutation Counts, Coverage, and Mutation Rates Across Samples

Figure 2.  Patients counts and rates file used to generate this plot: LGG-TP.patients.counts_and_rates.txt

CoMut Plot

Figure 3.  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: 11. 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
ATRX 1025950 253130 1422 82 73 73 2 0 1 1.3 7.8e-16 310 0.18 1.4e-11
TP53 160650 46920 412 116 88 65 2 0 4 3.6 2.3e-15 240 0.16 2.1e-11
IDH1 171190 44200 324 131 131 2 0 0 13 0.59 4.3e-15 390 0.16 2.6e-11
CIC 530060 192100 656 40 35 34 0 0 8 0.28 8.8e-15 130 0.16 3.4e-11
FUBP1 261630 77180 792 19 19 18 2 0 5 1.4 9.2e-15 93 0.16 3.4e-11
NOTCH1 678810 196180 760 25 16 22 2 0 20 1 5.1e-07 58 0.16 0.0016
PIK3R1 316880 81430 690 13 12 11 1 0 20 1.9 6.8e-07 48 0.16 0.0018
PIK3CA 441830 113050 792 15 15 10 0 0 20 1.3 1.3e-06 46 0.16 0.0031
IL32 69360 18190 218 4 4 1 0 0 20 0.92 8.3e-06 25 0.15 0.017
PTEN 165580 39780 348 8 8 8 0 0 20 1.2 0.000016 31 0.15 0.029
TIMD4 151130 46410 360 6 6 3 1 0 20 1.1 0.000028 30 0.15 0.046
CRIPAK 167280 55590 46 5 5 4 2 0 20 1.1 0.00012 25 0.18 0.18
NOX4 238340 64090 702 6 5 3 0 0 13 0.88 0.00027 25 0.15 0.37
CREBZF 127670 43350 30 4 4 1 0 0 20 1.4 0.00031 24 0.19 0.4
ZNRF2 37910 9520 362 3 2 3 0 0 20 0.73 0.0014 12 0.13 1
ATG5 115430 27710 280 3 3 3 0 0 20 1.5 0.0038 16 0.14 1
IDH2 156060 41140 358 6 6 2 0 0 20 1.1 0.0043 18 0.15 1
MUC7 140760 52360 88 8 5 7 0 0 20 1 0.0056 14 0.14 1
ARID1A 759390 223720 752 14 11 14 0 0 2 0.49 0.0082 54 0.19 1
EMG1 115600 35190 246 2 2 2 0 0 20 0.75 0.011 13 0.14 1
BTBD1 158950 41480 282 3 3 3 0 0 20 1 0.013 13 0.14 1
C3orf35 59160 18360 48 3 3 3 0 0 20 1.3 0.014 11 0.14 1
SMARCA4 550630 155720 1102 10 10 9 4 0 20 1.1 0.014 31 0.15 1
BCOR 605880 181220 410 7 7 7 3 0 20 1.6 0.015 28 0.16 1
DDX5 249900 68000 506 5 5 4 0 0 20 0.75 0.015 18 0.18 1
TCF12 298010 85340 802 6 6 5 0 0 7 3.4 0.016 32 0.16 1
GFRA4 14620 5610 54 1 1 1 0 0 20 0.56 0.017 7 0.15 1
SCAF1 251260 81940 336 4 4 2 0 0 20 0.37 0.018 18 0.15 1
SPANXN4 15300 3230 36 1 1 1 0 0 20 0.65 0.02 5.5 0.08 1
AP1S1 44030 11560 82 2 2 2 0 0 20 0.75 0.02 8.5 0.12 1
PAGE1 51000 13770 164 2 2 2 0 0 20 1.4 0.02 9.8 0.13 1
NKX2-2 92480 29070 70 3 3 3 0 0 20 1.1 0.02 11 0.13 1
SUMF2 159970 43180 384 3 2 3 1 0 17 0.43 0.021 11 0.13 1
UQCRH 40290 9860 166 2 2 2 0 0 20 0 0.021 7.3 0.11 1
OR11H12 119510 35020 50 4 3 4 0 0 20 1.3 0.021 11 0.13 1
ATRX

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

TP53

Figure S2.  This figure depicts the distribution of mutations and mutation types across the TP53 significant gene.

IDH1

Figure S3.  This figure depicts the distribution of mutations and mutation types across the IDH1 significant gene.

CIC

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

FUBP1

Figure S5.  This figure depicts the distribution of mutations and mutation types across the FUBP1 significant gene.

NOTCH1

Figure S6.  This figure depicts the distribution of mutations and mutation types across the NOTCH1 significant gene.

PIK3R1

Figure S7.  This figure depicts the distribution of mutations and mutation types across the PIK3R1 significant gene.

PIK3CA

Figure S8.  This figure depicts the distribution of mutations and mutation types across the PIK3CA significant gene.

IL32

Figure S9.  This figure depicts the distribution of mutations and mutation types across the IL32 significant gene.

PTEN

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

TIMD4

Figure S11.  This figure depicts the distribution of mutations and mutation types across the TIMD4 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

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

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