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 v2.0 was used to generate the results found in this report.
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Working with individual set: ACC-TP
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Number of patients in set: 90
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:ACC-TP.final_analysis_set.maf
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Blacklist used for this analysis: pancan_mutation_blacklist.v14.hg19.txt
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Significantly mutated genes (q ≤ 0.1): 208
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Mutations seen in COSMIC: 61
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Significantly mutated genes in COSMIC territory: 3
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Significantly mutated genesets: 21
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Significantly mutated genesets: (excluding sig. mutated genes):0
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Read 90 MAFs of type "maf1"
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Total number of mutations in input MAFs: 20147
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After removing 1222 blacklisted mutations: 18925
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After removing 579 noncoding mutations: 18346
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After collapsing adjacent/redundant mutations: 18337
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Number of mutations before filtering: 18337
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After removing 1275 mutations outside gene set: 17062
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After removing 65 mutations outside category set: 16997
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After removing 1 "impossible" mutations in
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gene-patient-category bins of zero coverage: 15656
Table 1. Get Full Table Table representing breakdown of mutations by type.
| type | count |
|---|---|
| De_novo_Start_InFrame | 3 |
| De_novo_Start_OutOfFrame | 2 |
| Frame_Shift_Del | 465 |
| Frame_Shift_Ins | 174 |
| In_Frame_Del | 236 |
| In_Frame_Ins | 80 |
| Missense_Mutation | 9572 |
| Nonsense_Mutation | 534 |
| Nonstop_Mutation | 6 |
| Silent | 5441 |
| Splice_Site | 459 |
| Start_Codon_Del | 5 |
| Start_Codon_SNP | 11 |
| Stop_Codon_Del | 7 |
| Stop_Codon_Ins | 2 |
| Total | 16997 |
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 |
|---|---|---|---|---|---|---|
| *CpG->T | 1918 | 159474080 | 0.000012 | 12 | 2.9 | 2.1 |
| *CpG->(G/A) | 658 | 159474080 | 4.1e-06 | 4.1 | 1 | 2.7 |
| *Cp(A/C/T)->mut | 4622 | 1285484037 | 3.6e-06 | 3.6 | 0.88 | 3.3 |
| A->mut | 2385 | 1372092527 | 1.7e-06 | 1.7 | 0.42 | 3.9 |
| indel+null | 1913 | 2817050644 | 6.8e-07 | 0.68 | 0.17 | NaN |
| double_null | 60 | 2817050644 | 2.1e-08 | 0.021 | 0.0052 | NaN |
| Total | 11556 | 2817050644 | 4.1e-06 | 4.1 | 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). If the figure is unpopulated, then full coverage is assumed (e.g. MutSig CV doesn't use WIGs and assumes full coverage).
Figure 1.
Figure 2. Patients counts and rates file used to generate this plot: ACC-TP.patients.counts_and_rates.txt
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.
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.
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: *CpG->(G/A)
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n3 = number of nonsilent mutations of type: *Cp(A/C/T)->mut
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n4 = number of nonsilent mutations of type: A->mut
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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_classic = p-value for the observed amount of nonsilent mutations being elevated in this gene
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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_cons = p-value for enrichment of mutations at evolutionarily most-conserved sites in gene
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p_joint = p-value for clustering + conservation
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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: 208. 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_classic | p_ns_s | p_clust | p_cons | p_joint | p | q |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | RNF222 | ring finger protein 222 | 30166 | 7 | 7 | 1 | 0 | 7 | 0 | 0 | 0 | 0 | 0 | 2.6e-12 | 0.061 | 2.6e-06 | 1 | 9.6e-06 | 9.99e-16 | 2.40e-13 |
| 2 | ZFPM1 | zinc finger protein, multitype 1 | 133160 | 91 | 47 | 5 | 0 | 0 | 0 | 4 | 0 | 66 | 21 | 1.3e-15 | 0.16 | 0 | 1 | 0 | <1.00e-15 | <2.40e-13 |
| 3 | GARS | glycyl-tRNA synthetase | 184616 | 35 | 34 | 3 | 6 | 1 | 0 | 33 | 1 | 0 | 0 | 5.4e-15 | 0.27 | 0 | 1 | 0 | <1.00e-15 | <2.40e-13 |
| 4 | ZNF517 | zinc finger protein 517 | 112718 | 34 | 33 | 2 | 0 | 0 | 0 | 0 | 34 | 0 | 0 | 2.8e-15 | 0.0076 | 0 | 1 | 0 | <1.00e-15 | <2.40e-13 |
| 5 | LRIG1 | leucine-rich repeats and immunoglobulin-like domains 1 | 282211 | 54 | 31 | 2 | 0 | 0 | 0 | 54 | 0 | 0 | 0 | 2.9e-15 | 6e-08 | 0 | 1 | 0 | <1.00e-15 | <2.40e-13 |
| 6 | LACTB | lactamase, beta | 116298 | 27 | 27 | 3 | 0 | 0 | 0 | 1 | 25 | 1 | 0 | 8.1e-15 | 0.0012 | 0 | 1 | 0 | <1.00e-15 | <2.40e-13 |
| 7 | OBSCN | obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF | 2164618 | 32 | 27 | 14 | 12 | 23 | 1 | 6 | 1 | 1 | 0 | 1 | 0.28 | 0 | 0.98 | 0 | <1.00e-15 | <2.40e-13 |
| 8 | CCDC102A | coiled-coil domain containing 102A | 83550 | 26 | 26 | 1 | 0 | 26 | 0 | 0 | 0 | 0 | 0 | 2.9e-15 | 0.00033 | 0 | 0.96 | 0 | <1.00e-15 | <2.40e-13 |
| 9 | OPRD1 | opioid receptor, delta 1 | 70226 | 26 | 26 | 1 | 1 | 0 | 0 | 26 | 0 | 0 | 0 | 1.1e-15 | 0.000065 | 0 | 1 | 0 | <1.00e-15 | <2.40e-13 |
| 10 | MUC5B | mucin 5B, oligomeric mucus/gel-forming | 1541207 | 29 | 25 | 13 | 8 | 3 | 0 | 5 | 21 | 0 | 0 | 0.00054 | 0.47 | 1e-06 | 0.022 | 0 | <1.00e-15 | <2.40e-13 |
| 11 | TOR3A | torsin family 3, member A | 96841 | 25 | 25 | 1 | 0 | 0 | 0 | 0 | 25 | 0 | 0 | 4.1e-15 | 0.03 | 0 | 1 | 0 | <1.00e-15 | <2.40e-13 |
| 12 | TRIOBP | TRIO and F-actin binding protein | 620852 | 24 | 23 | 4 | 0 | 0 | 0 | 2 | 21 | 1 | 0 | 9.8e-15 | 0.002 | 0 | 0.98 | 0 | <1.00e-15 | <2.40e-13 |
| 13 | MAL2 | mal, T-cell differentiation protein 2 | 37122 | 22 | 22 | 1 | 1 | 0 | 0 | 0 | 0 | 21 | 1 | 1.9e-15 | 1 | 0 | 0.84 | 0 | <1.00e-15 | <2.40e-13 |
| 14 | IRX3 | iroquois homeobox 3 | 75820 | 21 | 21 | 1 | 0 | 0 | 0 | 0 | 21 | 0 | 0 | 2.1e-15 | 0.056 | 0 | 1 | 0 | <1.00e-15 | <2.40e-13 |
| 15 | TPO | thyroid peroxidase | 229899 | 22 | 21 | 3 | 0 | 1 | 0 | 21 | 0 | 0 | 0 | 6.8e-15 | 0.001 | 0 | 0.56 | 0 | <1.00e-15 | <2.40e-13 |
| 16 | ASPDH | aspartate dehydrogenase domain containing | 74718 | 19 | 19 | 2 | 0 | 0 | 0 | 1 | 18 | 0 | 0 | 5.7e-15 | 0.0084 | 0 | 1 | 0 | <1.00e-15 | <2.40e-13 |
| 17 | ERCC2 | excision repair cross-complementing rodent repair deficiency, complementation group 2 (xeroderma pigmentosum D) | 196253 | 19 | 19 | 1 | 0 | 19 | 0 | 0 | 0 | 0 | 0 | 7.7e-15 | 0.0012 | 0 | 0 | 0 | <1.00e-15 | <2.40e-13 |
| 18 | GLTPD2 | glycolipid transfer protein domain containing 2 | 42201 | 19 | 19 | 1 | 2 | 0 | 19 | 0 | 0 | 0 | 0 | 4.4e-15 | 0.017 | 0 | 0.16 | 0 | <1.00e-15 | <2.40e-13 |
| 19 | KCNK17 | potassium channel, subfamily K, member 17 | 88332 | 19 | 19 | 2 | 0 | 0 | 0 | 1 | 18 | 0 | 0 | 3.9e-15 | 0.044 | 0 | 0.96 | 0 | <1.00e-15 | <2.40e-13 |
| 20 | RINL | Ras and Rab interactor-like | 102936 | 19 | 19 | 1 | 0 | 0 | 0 | 19 | 0 | 0 | 0 | 3.2e-15 | 0.003 | 0 | 0.53 | 0 | <1.00e-15 | <2.40e-13 |
| 21 | ZNF598 | zinc finger protein 598 | 183308 | 20 | 19 | 5 | 2 | 0 | 1 | 3 | 16 | 0 | 0 | 4.6e-15 | 0.23 | 0 | 1 | 0 | <1.00e-15 | <2.40e-13 |
| 22 | AMDHD1 | amidohydrolase domain containing 1 | 103268 | 18 | 18 | 1 | 15 | 0 | 0 | 0 | 18 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | <1.00e-15 | <2.40e-13 |
| 23 | FAM184B | family with sequence similarity 184, member B | 276441 | 18 | 18 | 3 | 1 | 17 | 0 | 1 | 0 | 0 | 0 | 7.6e-15 | 0.0074 | 0 | 1 | 0 | <1.00e-15 | <2.40e-13 |
| 24 | MUC2 | mucin 2, oligomeric mucus/gel-forming | 755805 | 21 | 18 | 15 | 8 | 3 | 0 | 16 | 1 | 1 | 0 | 0.1 | 0.5 | 0 | 0.99 | 0 | <1.00e-15 | <2.40e-13 |
| 25 | C1orf106 | chromosome 1 open reading frame 106 | 159139 | 16 | 16 | 2 | 0 | 15 | 0 | 0 | 1 | 0 | 0 | 5.6e-15 | 0.0062 | 0 | 1 | 0 | <1.00e-15 | <2.40e-13 |
| 26 | SEMA5B | sema domain, seven thrombospondin repeats (type 1 and type 1-like), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 5B | 275306 | 17 | 16 | 2 | 0 | 0 | 0 | 1 | 16 | 0 | 0 | 3.3e-15 | 0.043 | 0 | 0.99 | 0 | <1.00e-15 | <2.40e-13 |
| 27 | ADAD2 | adenosine deaminase domain containing 2 | 153125 | 15 | 15 | 1 | 0 | 0 | 0 | 15 | 0 | 0 | 0 | 1.1e-14 | 0.005 | 0 | 1 | 0 | <1.00e-15 | <2.40e-13 |
| 28 | KNDC1 | kinase non-catalytic C-lobe domain (KIND) containing 1 | 407586 | 17 | 15 | 5 | 10 | 0 | 0 | 2 | 15 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | <1.00e-15 | <2.40e-13 |
| 29 | PANK2 | pantothenate kinase 2 (Hallervorden-Spatz syndrome) | 122370 | 15 | 15 | 2 | 0 | 0 | 0 | 15 | 0 | 0 | 0 | 6.3e-15 | 0.024 | 0 | 1 | 0 | <1.00e-15 | <2.40e-13 |
| 30 | ATXN1 | ataxin 1 | 201752 | 15 | 14 | 9 | 1 | 0 | 1 | 4 | 0 | 10 | 0 | 8.8e-15 | 0.4 | 0 | 1 | 0 | <1.00e-15 | <2.40e-13 |
| 31 | C2orf81 | chromosome 2 open reading frame 81 | 152558 | 15 | 14 | 3 | 0 | 0 | 0 | 0 | 15 | 0 | 0 | 7.7e-15 | 0.029 | 0 | 1 | 0 | <1.00e-15 | <2.40e-13 |
| 32 | CTNNB1 | catenin (cadherin-associated protein), beta 1, 88kDa | 216091 | 14 | 14 | 9 | 0 | 0 | 0 | 4 | 6 | 4 | 0 | 9.6e-15 | 0.063 | 0 | 0.28 | 0 | <1.00e-15 | <2.40e-13 |
| 33 | FPGS | folylpolyglutamate synthase | 136084 | 14 | 14 | 2 | 0 | 0 | 0 | 1 | 13 | 0 | 0 | 3.9e-15 | 0.086 | 0 | 1 | 0 | <1.00e-15 | <2.40e-13 |
| 34 | IDUA | iduronidase, alpha-L- | 116170 | 14 | 14 | 4 | 1 | 2 | 0 | 0 | 12 | 0 | 0 | 1.1e-14 | 0.27 | 4e-07 | 0.0032 | 0 | <1.00e-15 | <2.40e-13 |
| 35 | SYT8 | synaptotagmin VIII | 99744 | 14 | 14 | 3 | 0 | 14 | 0 | 0 | 0 | 0 | 0 | 1.8e-15 | 0.0034 | 0 | 0.00066 | 0 | <1.00e-15 | <2.40e-13 |
Figure S1. This figure depicts the distribution of mutations and mutation types across the RNF222 significant gene.
Figure S2. This figure depicts the distribution of mutations and mutation types across the ZFPM1 significant gene.
Figure S3. This figure depicts the distribution of mutations and mutation types across the GARS significant gene.
Figure S4. This figure depicts the distribution of mutations and mutation types across the ZNF517 significant gene.
Figure S5. This figure depicts the distribution of mutations and mutation types across the LRIG1 significant gene.
Figure S6. This figure depicts the distribution of mutations and mutation types across the LACTB significant gene.
Figure S7. This figure depicts the distribution of mutations and mutation types across the OBSCN significant gene.
Figure S8. This figure depicts the distribution of mutations and mutation types across the CCDC102A significant gene.
Figure S9. This figure depicts the distribution of mutations and mutation types across the OPRD1 significant gene.
Figure S10. This figure depicts the distribution of mutations and mutation types across the MUC5B significant gene.
Figure S11. This figure depicts the distribution of mutations and mutation types across the TOR3A significant gene.
Figure S12. This figure depicts the distribution of mutations and mutation types across the TRIOBP significant gene.
Figure S13. This figure depicts the distribution of mutations and mutation types across the MAL2 significant gene.
Figure S14. This figure depicts the distribution of mutations and mutation types across the IRX3 significant gene.
Figure S15. This figure depicts the distribution of mutations and mutation types across the TPO significant gene.
Figure S16. This figure depicts the distribution of mutations and mutation types across the ASPDH significant gene.
Figure S17. This figure depicts the distribution of mutations and mutation types across the ERCC2 significant gene.
Figure S18. This figure depicts the distribution of mutations and mutation types across the GLTPD2 significant gene.
Figure S19. This figure depicts the distribution of mutations and mutation types across the KCNK17 significant gene.
Figure S20. This figure depicts the distribution of mutations and mutation types across the RINL significant gene.
Figure S21. This figure depicts the distribution of mutations and mutation types across the ZNF598 significant gene.
Figure S22. This figure depicts the distribution of mutations and mutation types across the AMDHD1 significant gene.
Figure S23. This figure depicts the distribution of mutations and mutation types across the FAM184B significant gene.
Figure S24. This figure depicts the distribution of mutations and mutation types across the MUC2 significant gene.
Figure S25. This figure depicts the distribution of mutations and mutation types across the C1orf106 significant gene.
Figure S26. This figure depicts the distribution of mutations and mutation types across the SEMA5B significant gene.
Figure S27. This figure depicts the distribution of mutations and mutation types across the ADAD2 significant gene.
Figure S28. This figure depicts the distribution of mutations and mutation types across the KNDC1 significant gene.
Figure S29. This figure depicts the distribution of mutations and mutation types across the PANK2 significant gene.
Figure S30. This figure depicts the distribution of mutations and mutation types across the ATXN1 significant gene.
Figure S31. This figure depicts the distribution of mutations and mutation types across the C2orf81 significant gene.
Figure S32. This figure depicts the distribution of mutations and mutation types across the CTNNB1 significant gene.
Figure S33. This figure depicts the distribution of mutations and mutation types across the FPGS significant gene.
Figure S34. This figure depicts the distribution of mutations and mutation types across the IDUA significant gene.
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: 3. Number of genes displayed: 10
| rank | gene | description | n | cos | n_cos | N_cos | cos_ev | p | q |
|---|---|---|---|---|---|---|---|---|---|
| 1 | CTNNB1 | catenin (cadherin-associated protein), beta 1, 88kDa | 14 | 138 | 14 | 12420 | 6397 | 2.4e-13 | 1.1e-09 |
| 2 | TP53 | tumor protein p53 | 19 | 356 | 18 | 32040 | 1630 | 5.8e-13 | 1.3e-09 |
| 3 | MEN1 | multiple endocrine neoplasia I | 8 | 208 | 5 | 18720 | 25 | 2.1e-08 | 0.000032 |
| 4 | ABCA12 | ATP-binding cassette, sub-family A (ABC1), member 12 | 3 | 1 | 1 | 90 | 1 | 0.00037 | 0.21 |
| 5 | ANKRD30A | ankyrin repeat domain 30A | 6 | 1 | 1 | 90 | 1 | 0.00037 | 0.21 |
| 6 | CCND2 | cyclin D2 | 1 | 1 | 1 | 90 | 1 | 0.00037 | 0.21 |
| 7 | KRTAP5-5 | keratin associated protein 5-5 | 6 | 1 | 1 | 90 | 0 | 0.00037 | 0.21 |
| 8 | LACE1 | lactation elevated 1 | 1 | 1 | 1 | 90 | 1 | 0.00037 | 0.21 |
| 9 | GRM3 | glutamate receptor, metabotropic 3 | 3 | 2 | 1 | 180 | 1 | 0.00074 | 0.33 |
| 10 | IGFBP3 | insulin-like growth factor binding protein 3 | 1 | 2 | 1 | 180 | 1 | 0.00074 | 0.33 |
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 A Ranked List of Significantly Mutated Genesets. (Source: MSigDB GSEA Cannonical Pathway Set).Number of significant genesets found: 21. 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 | FOLATE_BIOSYNTHESIS | ALPI, ALPL, ALPP, ALPP, ALPPL2, ALPPL2, DHFR, FPGS, GCH1, GGH, SPR | 9 | ALPI(1), ALPP(1), ALPPL2(8), FPGS(14), SPR(1) | 921600 | 25 | 23 | 7 | 2 | 0 | 9 | 3 | 13 | 0 | 0 | 0.041 | 7e-14 | 4.3e-11 | |
| 2 | STILBENE_COUMARINE_AND_LIGNIN_BIOSYNTHESIS | EPX, GBA3, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, TPO, TYR | 10 | EPX(1), PRDX1(1), PRDX2(2), TPO(22) | 1336570 | 26 | 25 | 7 | 2 | 3 | 0 | 21 | 0 | 2 | 0 | 0.016 | 1.6e-09 | 4.8e-07 | |
| 3 | SA_G1_AND_S_PHASES | Cdk2, 4, and 6 bind cyclin D in G1, while cdk2/cyclin E promotes the G1/S transition. | ARF1, ARF3, CCND1, CDK2, CDK4, CDKN1A, CDKN1B, CDKN2A, CFL1, E2F1, E2F2, MDM2, NXT1, PRB1, TP53 | 15 | ARF3(1), CDKN2A(2), MDM2(2), TP53(19) | 1124314 | 24 | 19 | 24 | 1 | 2 | 0 | 7 | 1 | 13 | 1 | 0.028 | 5.7e-09 | 1.2e-06 |
| 4 | HSA00940_PHENYLPROPANOID_BIOSYNTHESIS | Genes involved in phenylpropanoid biosynthesis | EPX, GBA, GBA3, LPO, MPO, PRDX6, TPO | 7 | EPX(1), TPO(22) | 1154920 | 23 | 22 | 4 | 2 | 2 | 0 | 21 | 0 | 0 | 0 | 0.018 | 2e-08 | 3.1e-06 |
| 5 | PMLPATHWAY | Ring-shaped PML nuclear bodies regulate transcription and are required co-activators in p53- and DAXX-mediated apoptosis. | CREBBP, DAXX, HRAS, PAX3, PML, PRAM-1, RARA, RB1, SIRT1, SP100, TNF, TNFRSF1A, TNFRSF1B, TNFRSF6, TNFSF6, TP53, UBL1 | 13 | CREBBP(1), DAXX(4), PML(2), RARA(1), RB1(2), SIRT1(1), TNFRSF1A(1), TP53(19) | 2553179 | 31 | 25 | 31 | 1 | 3 | 1 | 7 | 1 | 18 | 1 | 0.011 | 8.6e-08 | 0.000011 |
| 6 | P53PATHWAY | p53 induces cell cycle arrest or apoptosis under conditions of DNA damage. | APAF1, ATM, BAX, BCL2, CCND1, CCNE1, CDK2, CDK4, CDKN1A, E2F1, GADD45A, MDM2, PCNA, RB1, TIMP3, TP53 | 16 | APAF1(1), ATM(5), MDM2(2), RB1(2), TIMP3(1), TP53(19) | 2416850 | 30 | 24 | 30 | 2 | 2 | 0 | 6 | 1 | 20 | 1 | 0.086 | 2.2e-07 | 0.000021 |
| 7 | METHANE_METABOLISM | ADH5, ATP6V0C, SHMT1, CAT, EPX, LPO, MPO, PRDX1, PRDX2, PRDX5, PRDX6, SHMT1, SHMT2, TPO | 13 | ATP6V0C(1), EPX(1), PRDX1(1), PRDX2(2), SHMT2(1), TPO(22) | 1628686 | 28 | 27 | 9 | 3 | 4 | 0 | 22 | 0 | 2 | 0 | 0.025 | 2.4e-07 | 0.000021 | |
| 8 | RNAPATHWAY | dsRNA-activated protein kinase phosphorylates elF2a, which generally inhibits translation, and activates NF-kB to provoke inflammation. | CHUK, DNAJC3, EIF2S1, EIF2S2, MAP3K14, NFKB1, NFKBIA, PRKR, RELA, TP53 | 9 | NFKB1(1), TP53(19) | 1391271 | 20 | 18 | 20 | 0 | 2 | 0 | 5 | 1 | 11 | 1 | 0.023 | 4.6e-07 | 0.000034 |
| 9 | PLK3PATHWAY | Active Plk3 phosphorylates CDC25c, blocking the G2/M transition, and phosphorylates p53 to induce apoptosis. | ATM, ATR, CDC25C, CHEK1, CHEK2, CNK, TP53, YWHAH | 7 | ATM(5), ATR(3), CHEK2(2), TP53(19) | 2105624 | 29 | 25 | 29 | 3 | 3 | 0 | 6 | 3 | 16 | 1 | 0.28 | 5e-07 | 0.000034 |
| 10 | GSPATHWAY | Activated G-protein coupled receptors stimulate cAMP production and thus activate protein kinase A, involved in a number of signal transduction pathways. | ADCY1, GNAS, GNB1, GNGT1, PRKACA, PRKAR1A | 6 | ADCY1(1), GNAS(5), GNB1(3), PRKACA(1), PRKAR1A(7) | 921215 | 17 | 15 | 16 | 1 | 1 | 0 | 3 | 2 | 11 | 0 | 0.24 | 5.4e-07 | 0.000034 |
Table 6. 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 | GSPATHWAY | Activated G-protein coupled receptors stimulate cAMP production and thus activate protein kinase A, involved in a number of signal transduction pathways. | ADCY1, GNAS, GNB1, GNGT1, PRKACA, PRKAR1A | 5 | ADCY1(1), GNAS(5), GNB1(3), PRKACA(1) | 814601 | 10 | 8 | 10 | 1 | 1 | 0 | 3 | 2 | 4 | 0 | 0.42 | 0.017 | 1 |
| 2 | TERPENOID_BIOSYNTHESIS | FDFT1, FDPS, FDPS, LOC402397, IDI1, SQLE | 4 | FDFT1(1), IDI1(1), SQLE(2) | 449336 | 4 | 4 | 4 | 0 | 0 | 1 | 3 | 0 | 0 | 0 | 0.34 | 0.056 | 1 | |
| 3 | 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 | HLA-DRB1(3) | 328912 | 3 | 3 | 3 | 1 | 0 | 0 | 2 | 1 | 0 | 0 | 0.74 | 0.058 | 1 |
| 4 | EOSINOPHILSPATHWAY | Recruitment of eosinophils in the inflammatory response observed in asthma occurs via the chemoattractant eotaxin binding to the CCR3 receptor. | CCL11, CCL5, CCR3, CSF2, HLA-DRA, HLA-DRB1, IL3, IL5 | 8 | CCL11(1), CCR3(1), HLA-DRB1(3), IL3(1) | 407360 | 6 | 5 | 6 | 2 | 0 | 0 | 4 | 2 | 0 | 0 | 0.68 | 0.078 | 1 |
| 5 | CAPROLACTAM_DEGRADATION | AKR1A1, ECHS1, EHHADH, HADHA, SDS | 5 | AKR1A1(1), ECHS1(2), EHHADH(1), HADHA(1), SDS(1) | 665589 | 6 | 5 | 6 | 0 | 1 | 0 | 2 | 1 | 2 | 0 | 0.24 | 0.085 | 1 | |
| 6 | HSA00472_D_ARGININE_AND_D_ORNITHINE_METABOLISM | Genes involved in D-arginine and D-ornithine metabolism | DAO | 1 | DAO(1) | 97560 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0.72 | 0.098 | 1 |
| 7 | HSA00401_NOVOBIOCIN_BIOSYNTHESIS | Genes involved in novobiocin biosynthesis | GOT1, GOT2, TAT | 3 | GOT1(1), GOT2(2) | 356738 | 3 | 3 | 3 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 0.4 | 0.1 | 1 |
| 8 | SULFUR_METABOLISM | BPNT1, PAPSS1, PAPSS2, SULT1A2, SULT1A3, SULT1A3, SULT1A4, SULT1E1, SULT2A1, SUOX | 7 | BPNT1(3), PAPSS2(1), SUOX(2) | 815298 | 6 | 5 | 6 | 1 | 0 | 0 | 3 | 0 | 2 | 1 | 0.78 | 0.11 | 1 | |
| 9 | HSA00900_TERPENOID_BIOSYNTHESIS | Genes involved in terpenoid biosynthesis | FDFT1, FDPS, GGPS1, IDI1, IDI2, SQLE | 6 | FDFT1(1), IDI1(1), SQLE(2) | 590510 | 4 | 4 | 4 | 0 | 0 | 1 | 3 | 0 | 0 | 0 | 0.34 | 0.12 | 1 |
| 10 | UBIQUINONE_BIOSYNTHESIS | NDUFA1, NDUFA10, NDUFA11, NDUFA4, NDUFA5, NDUFA8, NDUFB2, NDUFB4, NDUFB5, NDUFB6, NDUFB7, NDUFS1, NDUFS2, NDUFV1, NDUFV2 | 15 | NDUFA1(1), NDUFA10(2), NDUFB5(2), NDUFB7(1), NDUFS2(1) | 964591 | 7 | 6 | 7 | 0 | 1 | 0 | 4 | 0 | 2 | 0 | 0.22 | 0.12 | 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.