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. MutSig v1.5 was used to generate the results found in this report.
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Working with individual set: KIRC-TP
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Number of patients in set: 417
The input for this pipeline is a set of individuals with the following files associated for each:
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An annotated .maf file describing the mutations called for the respective individual, and their properties.
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A .wig file that contains information about the coverage of the sample.
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MAF used for this analysis:KIRC-TP.final_analysis_set.maf
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Significantly mutated genes (q ≤ 0.1): 33
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Mutations seen in COSMIC: 452
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Significantly mutated genes in COSMIC territory: 109
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Genes with clustered mutations (≤ 3 aa apart): 504
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Significantly mutated genesets: 8
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Significantly mutated genesets: (excluding sig. mutated genes):0
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Read 183 MAFs of type "Broad"
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Read 169 MAFs of type "Baylor-Illumina"
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Read 120 MAFs of type "Baylor-SOLiD"
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Total number of mutations in input MAFs: 28827
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After removing 879 noncoding mutations: 27948
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After collapsing adjacent/redundant mutations: 27947
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Number of mutations before filtering: 27947
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After removing 581 mutations outside gene set: 27366
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After removing 39 mutations outside category set: 27327
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After removing 9 "impossible" mutations in
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gene-patient-category bins of zero coverage: 26698
Table 1. Get Full Table Table representing breakdown of mutations by type.
type | count |
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Frame_Shift_Del | 1543 |
Frame_Shift_Ins | 750 |
In_Frame_Del | 449 |
In_Frame_Ins | 142 |
Missense_Mutation | 16505 |
Nonsense_Mutation | 1132 |
Nonstop_Mutation | 3 |
Silent | 6245 |
Splice_Site | 535 |
Translation_Start_Site | 23 |
Total | 27327 |
Table 2. Get Full Table A breakdown of mutation rates per category discovered for this individual set.
category | n | N | rate | rate_per_mb | relative_rate | exp_ns_s_ratio |
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*CpG->T | 1575 | 645639745 | 2.4e-06 | 2.4 | 1.4 | 2.2 |
*Cp(A/C/T)->T | 2960 | 5584464449 | 5.3e-07 | 0.53 | 0.31 | 1.7 |
A->G | 2769 | 6109862055 | 4.5e-07 | 0.45 | 0.27 | 2.3 |
transver | 9214 | 12339966249 | 7.5e-07 | 0.75 | 0.44 | 5.1 |
indel+null | 4521 | 12339966249 | 3.7e-07 | 0.37 | 0.21 | NaN |
double_null | 36 | 12339966249 | 2.9e-09 | 0.0029 | 0.0017 | NaN |
Total | 21075 | 12339966249 | 1.7e-06 | 1.7 | 1 | 3.5 |
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.
![](KIRC-TP.covplot.png)
Figure 2. Patients counts and rates file used to generate this plot: KIRC-TP.patients.counts_and_rates.txt
![](KIRC-TP.bargraphs.png)
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.
![](KIRC-TP.final_analysis_set.maf.mutation_profile.png)
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.
![](KIRC-TP.final_analysis_set.maf.mutation_profile_AF.png)
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.
![](KIRC-TP_coMut.png)
Column Descriptions:
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N = number of sequenced bases in this gene across the individual set
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n = number of (nonsilent) mutations in this gene across the individual set
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npat = number of patients (individuals) with at least one nonsilent mutation
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nsite = number of unique sites having a non-silent mutation
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nsil = number of silent mutations in this gene across the individual set
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n1 = number of nonsilent mutations of type: *CpG->T
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n2 = number of nonsilent mutations of type: *Cp(A/C/T)->T
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n3 = number of nonsilent mutations of type: A->G
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n4 = number of nonsilent mutations of type: transver
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n5 = number of nonsilent mutations of type: indel+null
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n6 = number of nonsilent mutations of type: double_null
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p_ns_s = p-value for the observed nonsilent/silent ratio being elevated in this gene
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p = p-value (overall)
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q = q-value, False Discovery Rate (Benjamini-Hochberg procedure)
Table 3. Get Full Table A Ranked List of Significantly Mutated Genes. Number of significant genes found: 33. 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).
rank | gene | description | N | n | npat | nsite | nsil | n1 | n2 | n3 | n4 | n5 | n6 | p_ns_s | p | q |
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1 | PBRM1 | polybromo 1 | 2090589 | 139 | 137 | 129 | 4 | 0 | 2 | 5 | 17 | 114 | 1 | 0.000017 | <1.00e-15 | <8.64e-12 |
2 | SETD2 | SET domain containing 2 | 2968715 | 52 | 48 | 50 | 1 | 3 | 3 | 4 | 10 | 31 | 1 | 0.00059 | <1.00e-15 | <8.64e-12 |
3 | HGC6.3 | 104325 | 22 | 18 | 16 | 5 | 0 | 5 | 7 | 5 | 3 | 2 | 0.42 | 1.55e-15 | 8.64e-12 | |
4 | VHL | von Hippel-Lindau tumor suppressor | 155991 | 233 | 218 | 135 | 7 | 10 | 11 | 24 | 62 | 125 | 1 | 2.3e-13 | 1.89e-15 | 8.64e-12 |
5 | MUC4 | mucin 4, cell surface associated | 1332950 | 135 | 83 | 104 | 28 | 10 | 22 | 20 | 64 | 19 | 0 | 0.067 | 5.88e-15 | 1.57e-11 |
6 | PTEN | phosphatase and tensin homolog (mutated in multiple advanced cancers 1) | 519386 | 20 | 18 | 20 | 0 | 1 | 1 | 0 | 3 | 14 | 1 | 0.044 | 5.88e-15 | 1.57e-11 |
7 | KDM5C | lysine (K)-specific demethylase 5C | 1842978 | 27 | 27 | 27 | 1 | 1 | 1 | 1 | 7 | 17 | 0 | 0.059 | 6.00e-15 | 1.57e-11 |
8 | BAP1 | BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) | 867094 | 43 | 42 | 39 | 1 | 1 | 2 | 5 | 9 | 25 | 1 | 0.00069 | 7.11e-15 | 1.63e-11 |
9 | POTED | POTE ankyrin domain family, member D | 217403 | 8 | 8 | 6 | 0 | 1 | 1 | 6 | 0 | 0 | 0 | 0.049 | 6.96e-10 | 1.42e-06 |
10 | PABPC1 | poly(A) binding protein, cytoplasmic 1 | 793435 | 20 | 19 | 14 | 3 | 2 | 5 | 2 | 6 | 5 | 0 | 0.33 | 8.09e-09 | 1.48e-05 |
11 | TP53 | tumor protein p53 | 538821 | 10 | 9 | 10 | 1 | 2 | 1 | 2 | 3 | 2 | 0 | 0.2 | 3.96e-08 | 6.14e-05 |
12 | STAG3L2 | stromal antigen 3-like 2 | 114001 | 6 | 6 | 2 | 0 | 0 | 0 | 0 | 0 | 6 | 0 | 1 | 4.02e-08 | 6.14e-05 |
13 | NEFH | neurofilament, heavy polypeptide 200kDa | 900889 | 12 | 12 | 11 | 0 | 0 | 0 | 1 | 0 | 11 | 0 | 0.73 | 4.61e-08 | 6.49e-05 |
14 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 1343040 | 12 | 12 | 9 | 0 | 0 | 5 | 2 | 4 | 1 | 0 | 0.034 | 1.41e-06 | 0.00184 |
15 | PGPEP1L | pyroglutamyl-peptidase I-like | 230746 | 6 | 6 | 4 | 1 | 2 | 0 | 0 | 0 | 4 | 0 | 0.76 | 1.70e-06 | 0.00207 |
16 | KANK3 | KN motif and ankyrin repeat domains 3 | 338157 | 7 | 7 | 2 | 0 | 0 | 0 | 0 | 0 | 7 | 0 | 1 | 2.69e-06 | 0.00301 |
17 | PLAC4 | placenta-specific 4 | 144549 | 5 | 5 | 4 | 1 | 0 | 0 | 0 | 2 | 3 | 0 | 0.86 | 2.99e-06 | 0.00301 |
18 | HLA-DRB1 | major histocompatibility complex, class II, DR beta 1 | 256143 | 12 | 9 | 10 | 3 | 3 | 0 | 3 | 5 | 1 | 0 | 0.5 | 3.03e-06 | 0.00301 |
19 | C16orf3 | chromosome 16 open reading frame 3 | 83635 | 6 | 4 | 4 | 0 | 0 | 0 | 5 | 1 | 0 | 0 | 0.1 | 3.12e-06 | 0.00301 |
20 | CDKN2A | cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) | 227158 | 5 | 5 | 5 | 0 | 1 | 1 | 0 | 1 | 2 | 0 | 0.33 | 5.26e-06 | 0.00481 |
21 | MTOR | mechanistic target of rapamycin (serine/threonine kinase) | 3273597 | 26 | 25 | 22 | 3 | 0 | 3 | 4 | 19 | 0 | 0 | 0.077 | 5.87e-06 | 0.00512 |
22 | OR4C45 | olfactory receptor, family 4, subfamily C, member 45 | 233459 | 4 | 4 | 3 | 0 | 3 | 0 | 1 | 0 | 0 | 0 | 0.49 | 9.24e-06 | 0.00769 |
23 | MAGEC1 | melanoma antigen family C, 1 | 1425799 | 13 | 13 | 12 | 2 | 0 | 2 | 1 | 6 | 4 | 0 | 0.5 | 2.14e-05 | 0.0171 |
24 | ANKRD36 | ankyrin repeat domain 36 | 1554603 | 11 | 11 | 6 | 1 | 0 | 0 | 3 | 6 | 2 | 0 | 0.27 | 2.67e-05 | 0.0204 |
25 | KRTAP7-1 | keratin associated protein 7-1 | 63681 | 3 | 3 | 2 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0.84 | 3.32e-05 | 0.0242 |
26 | CD300E | CD300e molecule | 263865 | 5 | 5 | 5 | 0 | 0 | 3 | 1 | 1 | 0 | 0 | 0.13 | 3.43e-05 | 0.0242 |
27 | HLA-DRB5 | major histocompatibility complex, class II, DR beta 5 | 177471 | 8 | 7 | 7 | 2 | 1 | 1 | 0 | 3 | 3 | 0 | 0.53 | 3.96e-05 | 0.0269 |
28 | OR5P2 | olfactory receptor, family 5, subfamily P, member 2 | 403528 | 5 | 5 | 4 | 0 | 2 | 0 | 0 | 1 | 2 | 0 | 0.33 | 5.40e-05 | 0.0353 |
29 | TSPAN19 | tetraspanin 19 | 277310 | 5 | 5 | 5 | 0 | 0 | 1 | 0 | 2 | 2 | 0 | 0.54 | 5.71e-05 | 0.0361 |
30 | KRTAP4-1 | keratin associated protein 4-1 | 143366 | 4 | 4 | 4 | 1 | 0 | 1 | 0 | 1 | 2 | 0 | 0.77 | 6.60e-05 | 0.0403 |
31 | PLA2G4E | phospholipase A2, group IVE | 992841 | 8 | 8 | 5 | 0 | 1 | 0 | 1 | 1 | 5 | 0 | 0.46 | 0.000116 | 0.0688 |
32 | KRT1 | keratin 1 (epidermolytic hyperkeratosis) | 718983 | 7 | 7 | 3 | 0 | 1 | 0 | 0 | 0 | 6 | 0 | 0.75 | 0.000153 | 0.0877 |
33 | OR2T35 | olfactory receptor, family 2, subfamily T, member 35 | 148243 | 3 | 3 | 2 | 2 | 0 | 0 | 0 | 0 | 3 | 0 | 1 | 0.000158 | 0.0879 |
34 | TMEM37 | transmembrane protein 37 | 230679 | 4 | 4 | 3 | 0 | 1 | 0 | 1 | 0 | 2 | 0 | 0.52 | 0.000187 | 0.101 |
35 | PTPN18 | protein tyrosine phosphatase, non-receptor type 18 (brain-derived) | 467262 | 6 | 6 | 4 | 1 | 0 | 0 | 1 | 1 | 4 | 0 | 0.83 | 0.000200 | 0.105 |
In this analysis, COSMIC is used as a filter to increase power by restricting the territory of each gene. Cosmic version: v48.
Table 4. Get Full Table Significantly mutated genes (COSMIC territory only). To access the database please go to: COSMIC. Number of significant genes found: 109. Number of genes displayed: 10
rank | gene | description | n | cos | n_cos | N_cos | cos_ev | p | q |
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1 | VHL | von Hippel-Lindau tumor suppressor | 233 | 541 | 229 | 225597 | 5476 | 0 | 0 |
2 | PTEN | phosphatase and tensin homolog (mutated in multiple advanced cancers 1) | 20 | 767 | 20 | 319839 | 547 | 0 | 0 |
3 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 12 | 220 | 9 | 91740 | 3320 | 2.8e-12 | 4.3e-09 |
4 | TP53 | tumor protein p53 | 10 | 356 | 9 | 148452 | 1652 | 1.3e-11 | 1.5e-08 |
5 | EGFR | epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) | 7 | 293 | 6 | 122181 | 30 | 9.6e-08 | 0.000087 |
6 | CSF1R | colony stimulating factor 1 receptor, formerly McDonough feline sarcoma viral (v-fms) oncogene homolog | 5 | 14 | 3 | 5838 | 9 | 1.6e-07 | 0.00012 |
7 | STXBP3 | syntaxin binding protein 3 | 3 | 1 | 2 | 417 | 2 | 2.5e-07 | 0.00014 |
8 | TMEM47 | transmembrane protein 47 | 2 | 1 | 2 | 417 | 2 | 2.5e-07 | 0.00014 |
9 | CHEK2 | CHK2 checkpoint homolog (S. pombe) | 3 | 2 | 2 | 834 | 2 | 1e-06 | 0.00038 |
10 | KLK10 | kallikrein-related peptidase 10 | 3 | 2 | 2 | 834 | 2 | 1e-06 | 0.00038 |
Note:
n - number of (nonsilent) mutations in this gene across the individual set.
cos = number of unique mutated sites in this gene in COSMIC
n_cos = overlap between n and cos.
N_cos = number of individuals times cos.
cos_ev = total evidence: number of reports in COSMIC for mutations seen in this gene.
p = p-value for seeing the observed amount of overlap in this gene)
q = q-value, False Discovery Rate (Benjamini-Hochberg procedure)
Table 5. Get Full Table Genes with Clustered Mutations
num | gene | desc | n | mindist | nmuts0 | nmuts3 | nmuts12 | npairs0 | npairs3 | npairs12 |
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9469 | VHL | von Hippel-Lindau tumor suppressor | 233 | 0 | 287 | 837 | 2127 | 287 | 837 | 2127 |
5446 | MUC4 | mucin 4, cell surface associated | 135 | 0 | 43 | 70 | 180 | 43 | 70 | 180 |
437 | ANKRD36 | ankyrin repeat domain 36 | 11 | 0 | 11 | 11 | 13 | 11 | 11 | 13 |
806 | BAP1 | BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) | 43 | 0 | 10 | 15 | 35 | 10 | 15 | 35 |
9543 | WDR52 | WD repeat domain 52 | 9 | 0 | 10 | 10 | 10 | 10 | 10 | 10 |
9048 | TPSD1 | tryptase delta 1 | 7 | 0 | 9 | 21 | 21 | 9 | 21 | 21 |
5434 | MTOR | mechanistic target of rapamycin (serine/threonine kinase) | 26 | 0 | 7 | 11 | 20 | 7 | 11 | 20 |
6286 | PBRM1 | polybromo 1 | 139 | 0 | 6 | 18 | 68 | 6 | 18 | 68 |
5025 | MAP2K3 | mitogen-activated protein kinase kinase 3 | 9 | 0 | 6 | 15 | 16 | 6 | 15 | 16 |
7785 | SETD2 | SET domain containing 2 | 52 | 0 | 6 | 12 | 22 | 6 | 12 | 22 |
Note:
n - number of mutations in this gene in the individual set.
mindist - distance (in aa) between closest pair of mutations in this gene
npairs3 - how many pairs of mutations are within 3 aa of each other.
npairs12 - how many pairs of mutations are within 12 aa of each other.
Table 6. Get Full Table A Ranked List of Significantly Mutated Genesets. (Source: MSigDB GSEA Cannonical Pathway Set).Number of significant genesets found: 8. Number of genesets displayed: 10
rank | geneset | description | genes | N_genes | mut_tally | N | n | npat | nsite | nsil | n1 | n2 | n3 | n4 | n5 | n6 | p_ns_s | p | q |
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1 | HSA04120_UBIQUITIN_MEDIATED_PROTEOLYSIS | Genes involved in ubiquitin mediated proteolysis | ANAPC1, ANAPC10, ANAPC11, ANAPC2, ANAPC4, ANAPC5, ANAPC7, BTRC, CDC16, CDC20, CDC23, CDC26, CDC27, CUL1, CUL2, CUL3, FBXW11, FBXW7, FZR1, ITCH, LOC728919, RBX1, SKP1, SKP2, SMURF1, SMURF2, TCEB1, TCEB2, UBA1, UBE2C, UBE2D1, UBE2D2, UBE2D3, UBE2D4, UBE2E1, UBE2E2, UBE2E3, VHL, WWP1, WWP2 | 39 | ANAPC1(4), ANAPC11(1), ANAPC2(1), ANAPC4(1), ANAPC5(1), ANAPC7(2), BTRC(2), CDC16(2), CDC20(1), CDC23(2), CDC27(3), CUL1(3), CUL2(1), CUL3(5), FBXW11(1), FBXW7(1), FZR1(4), SKP2(1), SMURF2(3), TCEB1(4), TCEB2(1), UBA1(1), UBE2D1(2), UBE2D3(1), UBE2E2(1), VHL(233), WWP2(2) | 25294181 | 284 | 241 | 183 | 21 | 12 | 16 | 29 | 88 | 138 | 1 | 1.1e-07 | <1.00e-15 | <3.08e-13 |
2 | HIFPATHWAY | Under normal conditions, hypoxia inducible factor HIF-1 is degraded; under hypoxic conditions, it activates transcription of genes controlled by hpoxic response elements (HREs). | ARNT, ASPH, COPS5, CREB1, EDN1, EP300, EPO, HIF1A, HSPCA, JUN, LDHA, NOS3, P4HB, VEGF, VHL | 13 | ARNT(1), ASPH(3), COPS5(1), EP300(6), HIF1A(3), JUN(2), NOS3(2), VHL(233) | 10473682 | 251 | 228 | 153 | 15 | 10 | 11 | 29 | 71 | 129 | 1 | 1.1e-08 | <1.00e-15 | <3.08e-13 |
3 | VEGFPATHWAY | Vascular endothelial growth factor (VEGF) is upregulated by hypoxic conditions and promotes normal blood vessel formation and angiogenesis related to tumor growth or cardiac disease. | ARNT, EIF1, EIF1A, EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5, EIF2S1, EIF2S2, EIF2S3, ELAVL1, FLT1, FLT4, HIF1A, HRAS, KDR, NOS3, PIK3CA, PIK3R1, PLCG1, PRKCA, PRKCB1, PTK2, PXN, SHC1, VEGF, VHL | 25 | ARNT(1), EIF1(1), EIF2B1(2), EIF2B2(1), EIF2B3(1), EIF2B5(1), EIF2S2(1), EIF2S3(1), FLT1(4), FLT4(6), HIF1A(3), HRAS(1), KDR(5), NOS3(2), PIK3CA(12), PIK3R1(2), PTK2(1), SHC1(2), VHL(233) | 21044758 | 280 | 238 | 179 | 21 | 15 | 20 | 30 | 81 | 133 | 1 | 1.8e-08 | 1.89e-15 | 3.88e-13 |
4 | SA_PTEN_PATHWAY | PTEN is a tumor suppressor that dephosphorylates the lipid messenger phosphatidylinositol triphosphate. | AKT1, AKT2, AKT3, BPNT1, GRB2, ILK, MAPK1, MAPK3, PDK1, PIK3CA, PIK3CD, PIP3-E, PTEN, PTK2B, RBL2, SHC1, SOS1 | 16 | AKT1(2), AKT2(3), AKT3(2), GRB2(1), ILK(1), MAPK3(1), PDK1(1), PIK3CA(12), PTEN(20), PTK2B(2), RBL2(2), SHC1(2), SOS1(6) | 12480838 | 55 | 50 | 52 | 3 | 3 | 13 | 5 | 17 | 16 | 1 | 0.00026 | 8.50e-08 | 1.31e-05 |
5 | SA_TRKA_RECEPTOR | The TrkA receptor binds nerve growth factor to activate MAP kinase pathways and promote cell growth. | AKT1, AKT2, AKT3, ARHA, CDKN1A, ELK1, GRB2, HRAS, MAP2K1, MAP2K2, NGFB, NGFR, NTRK1, PIK3CA, PIK3CD, SHC1, SOS1 | 15 | AKT1(2), AKT2(3), AKT3(2), CDKN1A(1), ELK1(1), GRB2(1), HRAS(1), NGFR(1), NTRK1(4), PIK3CA(12), SHC1(2), SOS1(6) | 9746239 | 36 | 35 | 33 | 1 | 1 | 11 | 5 | 17 | 2 | 0 | 0.00027 | 1.70e-05 | 0.00209 |
6 | CDC42RACPATHWAY | PI3 kinase stimulates cell migration by activating cdc42, which activates ARP2/3, which in turn promotes formation of new actin fibers. | ACTR2, ACTR3, ARHA, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, CDC42, PAK1, PDGFRA, PIK3CA, PIK3R1, RAC1, WASL | 14 | ACTR2(1), ARPC1B(1), ARPC2(1), CDC42(1), PAK1(1), PDGFRA(7), PIK3CA(12), PIK3R1(2), RAC1(1), WASL(6) | 8358184 | 33 | 32 | 30 | 2 | 0 | 9 | 3 | 17 | 4 | 0 | 0.0081 | 8.07e-05 | 0.00829 |
7 | PTENPATHWAY | PTEN suppresses AKT-induced cell proliferation and antagonizes the action of PI3K. | AKT1, BCAR1, CDKN1B, FOXO3A, GRB2, ILK, ITGB1, MAPK1, MAPK3, PDK2, PDPK1, PIK3CA, PIK3R1, PTEN, PTK2, SHC1, SOS1, TNFSF6 | 16 | AKT1(2), BCAR1(3), GRB2(1), ILK(1), ITGB1(3), MAPK3(1), PDK2(1), PIK3CA(12), PIK3R1(2), PTEN(20), PTK2(1), SHC1(2), SOS1(6) | 11771993 | 55 | 50 | 52 | 6 | 3 | 11 | 4 | 19 | 17 | 1 | 0.018 | 0.000129 | 0.0114 |
8 | BBCELLPATHWAY | Fas ligand expression by T cells induces apoptosis in Fas-expressing, inactive B cells. | CD28, CD4, HLA-DRA, HLA-DRB1, TNFRSF5, TNFRSF6, TNFSF5, TNFSF6 | 4 | CD28(1), CD4(2), HLA-DRA(1), HLA-DRB1(12) | 1276465 | 16 | 13 | 14 | 3 | 4 | 1 | 3 | 6 | 2 | 0 | 0.3 | 0.000216 | 0.0167 |
9 | P53HYPOXIAPATHWAY | Hypoxia induces p53 accumulation and consequent apoptosis with p53-mediated cell cycle arrest, which is present under conditions of DNA damage. | ABCB1, AKT1, ATM, BAX, CDKN1A, CPB2, CSNK1A1, CSNK1D, FHL2, GADD45A, HIC1, HIF1A, HSPA1A, HSPCA, IGFBP3, MAPK8, MDM2, NFKBIB, NQO1, TP53 | 17 | ABCB1(4), AKT1(2), ATM(15), CDKN1A(1), CSNK1A1(1), FHL2(1), HIF1A(3), IGFBP3(1), NFKBIB(1), TP53(10) | 12308769 | 39 | 35 | 39 | 2 | 2 | 5 | 7 | 13 | 12 | 0 | 0.0037 | 0.00208 | 0.143 |
10 | MTORPATHWAY | Mammalian target of rapamycin (mTOR) senses mitogenic factors and nutrients, including ATP, and induces cell proliferation. | AKT1, EIF3S10, EIF4A1, EIF4A2, EIF4B, EIF4E, EIF4EBP1, EIF4G1, EIF4G2, EIF4G3, FKBP1A, FRAP1, MKNK1, PDK2, PDPK1, PIK3CA, PIK3R1, PPP2CA, PTEN, RPS6, RPS6KB1, TSC1, TSC2 | 21 | AKT1(2), EIF4A2(3), EIF4E(1), EIF4G1(2), EIF4G2(3), EIF4G3(3), MKNK1(1), PDK2(1), PIK3CA(12), PIK3R1(2), PPP2CA(1), PTEN(20), RPS6KB1(1), TSC1(2), TSC2(5) | 17176831 | 59 | 55 | 56 | 6 | 2 | 10 | 5 | 21 | 20 | 1 | 0.0063 | 0.00971 | 0.598 |
Table 7. Get Full Table A Ranked List of Significantly Mutated Genesets (Excluding Significantly Mutated Genes). Number of significant genesets found: 0. Number of genesets displayed: 10
rank | geneset | description | genes | N_genes | mut_tally | N | n | npat | nsite | nsil | n1 | n2 | n3 | n4 | n5 | n6 | p_ns_s | p | q |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | SA_TRKA_RECEPTOR | The TrkA receptor binds nerve growth factor to activate MAP kinase pathways and promote cell growth. | AKT1, AKT2, AKT3, ARHA, CDKN1A, ELK1, GRB2, HRAS, MAP2K1, MAP2K2, NGFB, NGFR, NTRK1, PIK3CA, PIK3CD, SHC1, SOS1 | 14 | AKT1(2), AKT2(3), AKT3(2), CDKN1A(1), ELK1(1), GRB2(1), HRAS(1), NGFR(1), NTRK1(4), SHC1(2), SOS1(6) | 8403199 | 24 | 24 | 24 | 1 | 1 | 6 | 3 | 13 | 1 | 0 | 0.009 | 0.0078 | 1 |
2 | UREACYCLEPATHWAY | Ammonia released from amino acid deamination is used to produce carbamoyl phosphate, which is used to convert ornithine to citrulline, from which urea is eventually formed. | ARG1, ASL, ASS, CPS1, GLS, GLUD1, GOT1 | 6 | ARG1(1), ASL(1), CPS1(6), GLS(4), GOT1(3) | 4816366 | 15 | 15 | 15 | 1 | 0 | 2 | 1 | 8 | 4 | 0 | 0.18 | 0.022 | 1 |
3 | HSA00950_ALKALOID_BIOSYNTHESIS_I | Genes involved in alkaloid biosynthesis I | DDC, GOT1, GOT2, TAT, TYR | 5 | DDC(2), GOT1(3), GOT2(2), TYR(3) | 2929848 | 10 | 10 | 10 | 1 | 0 | 0 | 3 | 2 | 5 | 0 | 0.44 | 0.022 | 1 |
4 | HSA00750_VITAMIN_B6_METABOLISM | Genes involved in vitamin B6 metabolism | AOX1, PDXK, PDXP, PNPO, PSAT1 | 5 | AOX1(7), PDXK(1), PDXP(1), PSAT1(1) | 2946049 | 10 | 10 | 10 | 0 | 1 | 1 | 0 | 6 | 2 | 0 | 0.14 | 0.024 | 1 |
5 | TCAPOPTOSISPATHWAY | HIV infection upregulates Fas ligand in macrophages and CD4 in helper T cells, leading to widespread Fas-induced T cell apoptosis. | CCR5, CD28, CD3D, CD3E, CD3G, CD3Z, CD4, TNFRSF6, TNFSF6, TRA@, TRB@ | 6 | CCR5(3), CD28(1), CD3E(2), CD3G(1), CD4(2) | 2024848 | 9 | 7 | 8 | 0 | 1 | 2 | 1 | 5 | 0 | 0 | 0.07 | 0.034 | 1 |
6 | EEA1PATHWAY | The FYVE-finger proteins EEA1 and HRS are localized to endosome membranes and regulate sorting and ubiquitination in the vesicle transport system. | EEA1, EGF, EGFR, HGS, RAB5A, TF, TFRC | 7 | EEA1(5), EGF(4), EGFR(7), HGS(2), RAB5A(1) | 7898260 | 19 | 19 | 18 | 0 | 3 | 1 | 5 | 5 | 5 | 0 | 0.01 | 0.038 | 1 |
7 | IFNGPATHWAY | IFN gamma signaling pathway | IFNG, IFNGR1, IFNGR2, JAK1, JAK2, STAT1 | 6 | IFNGR1(2), IFNGR2(1), JAK1(4), JAK2(5), STAT1(4) | 5136758 | 16 | 16 | 16 | 2 | 1 | 0 | 1 | 10 | 4 | 0 | 0.4 | 0.038 | 1 |
8 | CYSTEINE_METABOLISM | CARS, CTH, GOT1, GOT2, LDHA, LDHB, LDHC, MPST | 8 | CARS(4), CTH(1), GOT1(3), GOT2(2), LDHB(1), LDHC(1), MPST(2) | 4180017 | 14 | 14 | 14 | 2 | 1 | 0 | 2 | 6 | 5 | 0 | 0.47 | 0.046 | 1 | |
9 | CDC42RACPATHWAY | PI3 kinase stimulates cell migration by activating cdc42, which activates ARP2/3, which in turn promotes formation of new actin fibers. | ACTR2, ACTR3, ARHA, ARPC1A, ARPC1B, ARPC2, ARPC3, ARPC4, CDC42, PAK1, PDGFRA, PIK3CA, PIK3R1, RAC1, WASL | 13 | ACTR2(1), ARPC1B(1), ARPC2(1), CDC42(1), PAK1(1), PDGFRA(7), PIK3R1(2), RAC1(1), WASL(6) | 7015144 | 21 | 20 | 21 | 2 | 0 | 4 | 1 | 13 | 3 | 0 | 0.12 | 0.047 | 1 |
10 | STILBENE_COUMARINE_AND_LIGNIN_BIOSYNTHESIS | EPX, GBA3, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, TPO, TYR | 10 | EPX(1), GBA3(2), MPO(4), PRDX1(1), PRDX5(1), TPO(3), TYR(3) | 5954630 | 15 | 15 | 15 | 1 | 1 | 2 | 5 | 5 | 2 | 0 | 0.077 | 0.05 | 1 |
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]
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.