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: MOLECULAR_NONSMOKER
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Number of patients in set: 50
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:MOLECULAR_NONSMOKER.final_analysis_set.maf
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Significantly mutated genes (q ≤ 0.1): 11
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Mutations seen in COSMIC: 75
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Significantly mutated genes in COSMIC territory: 11
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Genes with clustered mutations (≤ 3 aa apart): 21
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Significantly mutated genesets: 32
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Significantly mutated genesets: (excluding sig. mutated genes):0
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Read 50 MAFs of type "Broad"
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Total number of mutations in input MAFs: 15943
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After removing 3 mutations outside chr1-24: 15940
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After removing 217 blacklisted mutations: 15723
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After removing 8240 noncoding mutations: 7483
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After collapsing adjacent/redundant mutations: 6362
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Number of mutations before filtering: 6362
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After removing 71 mutations outside gene set: 6291
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After removing 3 mutations outside category set: 6288
type | count |
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Frame_Shift_Del | 100 |
Frame_Shift_Ins | 52 |
In_Frame_Del | 36 |
In_Frame_Ins | 6 |
Missense_Mutation | 4048 |
Nonsense_Mutation | 304 |
Nonstop_Mutation | 5 |
Silent | 1616 |
Splice_Site | 116 |
Translation_Start_Site | 5 |
Total | 6288 |
category | n | N | rate | rate_per_mb | relative_rate | exp_ns_s_ratio |
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*CpG->mut | 912 | 82813800 | 0.000011 | 11 | 3.5 | 2.5 |
Tp*Cp(A/C/T)->mut | 1295 | 179865450 | 7.2e-06 | 7.2 | 2.3 | 3.3 |
(A/C/G)p*Cp(A/C/T)->mut | 1079 | 498848200 | 2.2e-06 | 2.2 | 0.69 | 3.3 |
A->mut | 767 | 732518300 | 1e-06 | 1 | 0.33 | 3.9 |
indel+null | 616 | 1494045750 | 4.1e-07 | 0.41 | 0.13 | NaN |
double_null | 3 | 1494045750 | 2e-09 | 0.002 | 0.00064 | NaN |
Total | 4672 | 1494045750 | 3.1e-06 | 3.1 | 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).
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->mut
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n2 = number of nonsilent mutations of type: Tp*Cp(A/C/T)->mut
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n3 = number of nonsilent mutations of type: (A/C/G)p*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)
rank | gene | description | N | n | npat | nsite | nsil | n1 | n2 | n3 | n4 | n5 | n6 | p_classic | p_ns_s | p_cons | p_joint | p | q |
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1 | TP53 | tumor protein p53 | 62900 | 19 | 17 | 17 | 0 | 2 | 2 | 2 | 2 | 11 | 0 | 1.1e-14 | 0.017 | NaN | NaN | 1.1e-14 | 2e-10 |
2 | EGFR | epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) | 200450 | 12 | 10 | 7 | 0 | 0 | 0 | 2 | 6 | 4 | 0 | 1e-11 | 0.2 | NaN | NaN | 1e-11 | 9.1e-08 |
3 | CDKN2A | cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) | 49350 | 5 | 5 | 5 | 0 | 0 | 0 | 1 | 1 | 3 | 0 | 5.4e-08 | 0.51 | NaN | NaN | 5.4e-08 | 0.00033 |
4 | SMAD4 | SMAD family member 4 | 85150 | 5 | 5 | 5 | 0 | 2 | 1 | 0 | 0 | 2 | 0 | 1.6e-07 | 0.31 | NaN | NaN | 1.6e-07 | 0.00072 |
5 | KRAS | v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog | 35350 | 4 | 4 | 2 | 0 | 0 | 0 | 4 | 0 | 0 | 0 | 3.7e-07 | 0.54 | NaN | NaN | 3.7e-07 | 0.0013 |
6 | KEAP1 | kelch-like ECH-associated protein 1 | 91450 | 6 | 6 | 6 | 0 | 3 | 1 | 0 | 1 | 1 | 0 | 5.9e-07 | 0.16 | NaN | NaN | 5.9e-07 | 0.0018 |
7 | CSMD3 | CUB and Sushi multiple domains 3 | 573500 | 10 | 10 | 10 | 0 | 1 | 2 | 4 | 3 | 0 | 0 | 1e-06 | 0.11 | NaN | NaN | 1e-06 | 0.0027 |
8 | BRAF | v-raf murine sarcoma viral oncogene homolog B1 | 111550 | 5 | 5 | 4 | 0 | 0 | 2 | 0 | 3 | 0 | 0 | 0.000018 | 0.29 | NaN | NaN | 0.000018 | 0.041 |
9 | SPTA1 | spectrin, alpha, erythrocytic 1 (elliptocytosis 2) | 373400 | 7 | 7 | 6 | 1 | 0 | 1 | 5 | 0 | 1 | 0 | 0.000034 | 0.46 | NaN | NaN | 0.000034 | 0.063 |
10 | STK11 | serine/threonine kinase 11 | 43500 | 3 | 3 | 3 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0.000035 | 0.44 | NaN | NaN | 0.000035 | 0.063 |
11 | OR4A5 | olfactory receptor, family 4, subfamily A, member 5 | 47600 | 3 | 3 | 3 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 0.000055 | 0.38 | NaN | NaN | 0.000055 | 0.09 |
12 | SETD2 | SET domain containing 2 | 319150 | 6 | 5 | 6 | 0 | 0 | 0 | 0 | 1 | 4 | 1 | 0.000071 | 0.31 | NaN | NaN | 0.000071 | 0.11 |
13 | MGAT4C | mannosyl (alpha-1,3-)-glycoprotein beta-1,4-N-acetylglucosaminyltransferase, isozyme C (putative) | 72450 | 3 | 3 | 3 | 0 | 2 | 0 | 0 | 1 | 0 | 0 | 0.000084 | 0.59 | NaN | NaN | 0.000084 | 0.11 |
14 | CDH10 | cadherin 10, type 2 (T2-cadherin) | 120550 | 4 | 4 | 4 | 0 | 2 | 0 | 2 | 0 | 0 | 0 | 0.000089 | 0.37 | NaN | NaN | 0.000089 | 0.11 |
15 | KRTAP4-11 | keratin associated protein 4-11 | 27950 | 2 | 2 | 2 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0.000093 | 0.58 | NaN | NaN | 0.000093 | 0.11 |
16 | U2AF2 | U2 small nuclear RNA auxiliary factor 2 | 71100 | 3 | 3 | 3 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0.00014 | 0.62 | NaN | NaN | 0.00014 | 0.16 |
17 | CRIPAK | cysteine-rich PAK1 inhibitor | 61350 | 3 | 3 | 2 | 1 | 1 | 0 | 0 | 0 | 2 | 0 | 0.00024 | 0.9 | NaN | NaN | 0.00024 | 0.24 |
18 | FAM5C | family with sequence similarity 5, member C | 116450 | 4 | 4 | 4 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 0.00026 | 0.7 | NaN | NaN | 0.00026 | 0.24 |
19 | GRM1 | glutamate receptor, metabotropic 1 | 184100 | 5 | 5 | 5 | 0 | 2 | 3 | 0 | 0 | 0 | 0 | 0.00026 | 0.15 | NaN | NaN | 0.00026 | 0.24 |
20 | HSD3B1 | hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 | 56700 | 3 | 3 | 3 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0.00029 | 0.42 | NaN | NaN | 0.00029 | 0.26 |
21 | OR2W5 | olfactory receptor, family 2, subfamily W, member 5 | 48350 | 3 | 3 | 3 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0.0003 | 0.43 | NaN | NaN | 0.0003 | 0.26 |
22 | OR2M4 | olfactory receptor, family 2, subfamily M, member 4 | 46950 | 3 | 3 | 3 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0.00034 | 0.41 | NaN | NaN | 0.00034 | 0.28 |
23 | FRMD8 | FERM domain containing 8 | 51200 | 3 | 3 | 3 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 0.00036 | 0.34 | NaN | NaN | 0.00036 | 0.28 |
24 | PAK1IP1 | PAK1 interacting protein 1 | 60950 | 3 | 3 | 3 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 0.00038 | 0.37 | NaN | NaN | 0.00038 | 0.28 |
25 | OR2C3 | olfactory receptor, family 2, subfamily C, member 3 | 48350 | 3 | 3 | 3 | 0 | 0 | 2 | 1 | 0 | 0 | 0 | 0.00039 | 0.22 | NaN | NaN | 0.00039 | 0.28 |
26 | ASCL3 | achaete-scute complex homolog 3 (Drosophila) | 27500 | 2 | 2 | 2 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0.00043 | 0.63 | NaN | NaN | 0.00043 | 0.29 |
27 | FMO3 | flavin containing monooxygenase 3 | 81550 | 3 | 3 | 3 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0.00043 | 0.53 | NaN | NaN | 0.00043 | 0.29 |
28 | PBX2 | pre-B-cell leukemia homeobox 2 | 59050 | 3 | 3 | 3 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 0.00045 | 0.53 | NaN | NaN | 0.00045 | 0.29 |
29 | MET | met proto-oncogene (hepatocyte growth factor receptor) | 215350 | 4 | 4 | 4 | 0 | 0 | 0 | 0 | 1 | 3 | 0 | 0.00048 | 0.51 | NaN | NaN | 0.00048 | 0.29 |
30 | SKIV2L2 | superkiller viralicidic activity 2-like 2 (S. cerevisiae) | 161850 | 4 | 4 | 4 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 0.00048 | 0.8 | NaN | NaN | 0.00048 | 0.29 |
31 | G3BP1 | GTPase activating protein (SH3 domain) binding protein 1 | 72250 | 3 | 3 | 3 | 0 | 0 | 0 | 2 | 1 | 0 | 0 | 0.00053 | 0.51 | NaN | NaN | 0.00053 | 0.31 |
32 | CST5 | cystatin D | 22050 | 2 | 2 | 2 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0.00057 | 0.56 | NaN | NaN | 0.00057 | 0.32 |
33 | CTNNB1 | catenin (cadherin-associated protein), beta 1, 88kDa | 120100 | 3 | 3 | 3 | 0 | 0 | 2 | 0 | 1 | 0 | 0 | 0.0007 | 0.48 | NaN | NaN | 0.0007 | 0.36 |
34 | DCAF4L2 | DDB1 and CUL4 associated factor 4-like 2 | 59600 | 3 | 3 | 3 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0.0007 | 0.4 | NaN | NaN | 0.0007 | 0.36 |
35 | DNAJB7 | DnaJ (Hsp40) homolog, subfamily B, member 7 | 46700 | 2 | 2 | 2 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0.00072 | 0.66 | NaN | NaN | 0.00072 | 0.36 |
In this analysis, COSMIC is used as a filter to increase power by restricting the territory of each gene. Cosmic version: v48.
rank | gene | description | n | cos | n_cos | N_cos | cos_ev | p | q |
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1 | TP53 | tumor protein p53 | 19 | 356 | 18 | 17800 | 2191 | 0 | 0 |
2 | EGFR | epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) | 12 | 293 | 12 | 14650 | 5627 | 0 | 0 |
3 | BRAF | v-raf murine sarcoma viral oncogene homolog B1 | 5 | 89 | 5 | 4450 | 28829 | 4.2e-12 | 6.3e-09 |
4 | KRAS | v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog | 4 | 52 | 4 | 2600 | 57936 | 1.8e-10 | 2e-07 |
5 | CDKN2A | cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) | 5 | 332 | 5 | 16600 | 93 | 3e-09 | 2.7e-06 |
6 | SMAD4 | SMAD family member 4 | 5 | 159 | 4 | 7950 | 17 | 1.6e-08 | 0.000012 |
7 | MET | met proto-oncogene (hepatocyte growth factor receptor) | 4 | 34 | 3 | 1700 | 9 | 2.5e-08 | 0.000016 |
8 | CTNNB1 | catenin (cadherin-associated protein), beta 1, 88kDa | 3 | 138 | 3 | 6900 | 1551 | 1.6e-06 | 0.00093 |
9 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 3 | 220 | 3 | 11000 | 1965 | 6.6e-06 | 0.0033 |
10 | APOBEC3G | apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G | 1 | 1 | 1 | 50 | 1 | 0.00016 | 0.064 |
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)
num | gene | desc | n | mindist | nmuts0 | nmuts3 | nmuts12 | npairs0 | npairs3 | npairs12 |
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958 | EGFR | epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) | 12 | 0 | 10 | 10 | 10 | 10 | 10 | 10 |
1667 | KRAS | v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog | 4 | 0 | 6 | 6 | 6 | 6 | 6 | 6 |
3278 | TP53 | tumor protein p53 | 19 | 0 | 2 | 6 | 22 | 2 | 6 | 22 |
3040 | SPTA1 | spectrin, alpha, erythrocytic 1 (elliptocytosis 2) | 7 | 0 | 1 | 2 | 2 | 1 | 2 | 2 |
303 | BRAF | v-raf murine sarcoma viral oncogene homolog B1 | 5 | 0 | 1 | 1 | 3 | 1 | 1 | 3 |
485 | CBWD1 | COBW domain containing 1 | 2 | 0 | 1 | 1 | 1 | 1 | 1 | 1 |
2971 | SMAD4 | SMAD family member 4 | 5 | 0 | 1 | 1 | 1 | 1 | 1 | 1 |
3116 | TACC2 | transforming, acidic coiled-coil containing protein 2 | 2 | 0 | 1 | 1 | 1 | 1 | 1 | 1 |
262 | BAIAP3 | BAI1-associated protein 3 | 2 | 1 | 0 | 1 | 1 | 0 | 1 | 1 |
476 | CARM1 | coactivator-associated arginine methyltransferase 1 | 2 | 1 | 0 | 1 | 1 | 0 | 1 | 1 |
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.
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 | 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 | CCND1(1), CDK4(1), CDKN2A(5), TP53(19) | 646050 | 26 | 18 | 24 | 1 | 4 | 2 | 3 | 3 | 14 | 0 | 0.016 | <1.00e-15 | <6.16e-13 |
2 | 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(2), TP53(19) | 736450 | 21 | 18 | 19 | 1 | 3 | 2 | 3 | 2 | 11 | 0 | 0.05 | 2.34e-14 | 7.22e-12 |
3 | 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(2), ATR(2), TP53(19) | 1204700 | 23 | 19 | 21 | 1 | 3 | 4 | 2 | 3 | 11 | 0 | 0.058 | 1.17e-12 | 2.15e-10 |
4 | RBPATHWAY | The ATM protein kinase recognizes DNA damage and blocks cell cycle progression by phosphorylating chk1 and p53, which normally inhibits Rb to allow G1/S transitions. | ATM, CDC2, CDC25A, CDC25B, CDC25C, CDK2, CDK4, CHEK1, MYT1, RB1, TP53, WEE1, YWHAH | 12 | ATM(2), CDK4(1), RB1(1), TP53(19) | 1325400 | 23 | 20 | 21 | 1 | 4 | 2 | 2 | 3 | 12 | 0 | 0.038 | 1.39e-12 | 2.15e-10 |
5 | TERTPATHWAY | hTERC, the RNA subunit of telomerase, and hTERT, the catalytic protein subunit, are required for telomerase activity and are overexpressed in many cancers. | HDAC1, MAX, MYC, SP1, SP3, TP53, WT1, ZNF42 | 7 | MAX(1), TP53(19) | 530100 | 20 | 18 | 18 | 3 | 2 | 2 | 2 | 2 | 12 | 0 | 0.3 | 2.33e-12 | 2.87e-10 |
6 | TELPATHWAY | Telomerase is a ribonucleotide protein that adds telomeric repeats to the 3' ends of chromosomes. | AKT1, BCL2, EGFR, G22P1, HSPCA, IGF1R, KRAS2, MYC, POLR2A, PPP2CA, PRKCA, RB1, TEP1, TERF1, TERT, TNKS, TP53, XRCC5 | 15 | EGFR(12), IGF1R(2), POLR2A(2), PRKCA(1), RB1(1), TEP1(2), TP53(19), XRCC5(2) | 2114100 | 41 | 24 | 34 | 1 | 2 | 3 | 8 | 10 | 18 | 0 | 0.00098 | 3.22e-12 | 3.31e-10 |
7 | 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(2), RARA(1), RB1(1), SP100(1), TP53(19) | 1445900 | 24 | 20 | 22 | 0 | 2 | 2 | 4 | 3 | 13 | 0 | 0.0032 | 1.31e-11 | 1.15e-09 |
8 | TIDPATHWAY | On ligand binding, interferon gamma receptors stimulate JAK2 kinase to phosphorylate STAT transcription factors, which promote expression of interferon responsive genes. | DNAJA3, HSPA1A, IFNG, IFNGR1, IFNGR2, IKBKB, JAK2, LIN7A, NFKB1, NFKBIA, RB1, RELA, TIP-1, TNF, TNFRSF1A, TNFRSF1B, TP53, USH1C, WT1 | 18 | IKBKB(1), NFKB1(2), RB1(1), TP53(19) | 1382600 | 23 | 20 | 21 | 1 | 3 | 3 | 3 | 2 | 12 | 0 | 0.022 | 1.72e-11 | 1.32e-09 |
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 | 19 | ATM(2), BAX(1), MAPK8(1), TP53(19) | 1566000 | 23 | 19 | 21 | 1 | 3 | 3 | 3 | 3 | 11 | 0 | 0.035 | 2.31e-10 | 1.58e-08 |
10 | 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 | ATM(2), BAX(1), CCND1(1), CDK4(1), RB1(1), TP53(19) | 1368250 | 25 | 21 | 23 | 3 | 5 | 2 | 3 | 3 | 12 | 0 | 0.14 | 7.70e-10 | 4.75e-08 |
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 | NFATPATHWAY | Cardiac hypertrophy is induced by NF-ATc4 and GATA4, which are stimulated through calcineurin activated by CaMK. | ACTA1, AGT, AKT1, CALM1, CALM2, CALM3, CALR, CAMK1, CAMK1G, CAMK4, CREBBP, CSNK1A1, CTF1, DTR, EDN1, ELSPBP1, F2, FGF2, FKBP1A, GATA4, GSK3B, HAND1, HAND2, HRAS, IGF1, LIF, MAP2K1, MAPK1, MAPK14, MAPK3, MAPK8, MEF2C, MYH2, NFATC1, NFATC2, NFATC3, NFATC4, NKX2-5, NPPA, PIK3CA, PIK3R1, PPP3CA, PPP3CB, PPP3CC, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B, RAF1, RPS6KB1, SYT1 | 51 | CAMK1(1), CAMK4(1), CREBBP(2), IGF1(1), LIF(1), MAPK8(1), MYH2(1), NFATC2(1), NFATC3(1), NFATC4(1), NKX2-5(1), NPPA(1), PIK3CA(3), PPP3CA(2), PPP3CB(1), PPP3CC(1) | 3808800 | 20 | 20 | 20 | 1 | 1 | 8 | 6 | 2 | 3 | 0 | 0.034 | 0.00044 | 0.27 |
2 | CK1PATHWAY | Caseine kinase 1 (CK1) and cdk5 phosphorylate DARPP32 in the dopamine signaling pathway. | CDK5, CDK5R1, CSNK1D, DRD1, DRD2, GRM1, PLCB1, PPP1CA, PPP1R1B, PPP2CA, PPP3CA, PRKACB, PRKACG, PRKAR1A, PRKAR1B, PRKAR2A, PRKAR2B | 17 | DRD2(2), GRM1(5), PPP1R1B(1), PPP3CA(2) | 1211600 | 10 | 9 | 10 | 0 | 2 | 3 | 3 | 2 | 0 | 0 | 0.058 | 0.0046 | 1 |
3 | GSK3PATHWAY | Bacterial lipopolysaccharide activates AKT to promote the survival and activation of macrophages and inhibits Gsk3-beta to promote beta-catenin accumulation in the nucleus. | AKT1, APC, AXIN1, CCND1, CD14, CTNNB1, DVL1, FZD1, GJA1, GNAI1, GSK3B, IRAK1, LBP, LEF1, LY96, MYD88, NFKB1, PDPK1, PIK3CA, PIK3R1, PPP2CA, PRKR, RELA, TIRAP, TLR4, TOLLIP, WNT1 | 26 | APC(1), CCND1(1), CD14(1), CTNNB1(3), LEF1(1), MYD88(1), NFKB1(2), PIK3CA(3), TLR4(3) | 2310000 | 16 | 12 | 16 | 1 | 4 | 5 | 2 | 4 | 1 | 0 | 0.076 | 0.015 | 1 |
4 | 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 | ASL(1), CPS1(3), GOT1(1) | 584650 | 5 | 5 | 5 | 1 | 1 | 1 | 2 | 0 | 1 | 0 | 0.59 | 0.017 | 1 |
5 | RANKLPATHWAY | RANK is a TNF-type receptor that promotes osteoclast differentiation and consequent bone resorbtion on binding RANK ligand produced by osteoblasts. | FOS, FOSL1, FOSL2, IFNAR1, IFNAR2, IFNB1, ISGF3G, MAPK8, NFKB1, PRKR, RELA, TNFRSF11A, TNFSF11, TRAF6 | 12 | FOSL1(1), MAPK8(1), NFKB1(2), TNFRSF11A(2), TRAF6(1) | 834150 | 7 | 6 | 7 | 0 | 2 | 2 | 2 | 0 | 1 | 0 | 0.13 | 0.018 | 1 |
6 | FLUMAZENILPATHWAY | Flumazenil is a benzodiazepine receptor antagonist that may induce protective preconditioning in ischemic cardiomyocytes. | GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GPX1, PRKCE, SOD1 | 9 | GABRA1(1), GABRA2(2), GABRA5(1), PRKCE(1) | 596250 | 5 | 5 | 5 | 1 | 1 | 0 | 1 | 2 | 1 | 0 | 0.58 | 0.019 | 1 |
7 | TOLLPATHWAY | Toll-like receptors are activated by bacterial lipoproteins, lipopolysaccharides, and other surface molecules, and activate pro-inflammatory factors such as NF-kB. | CD14, CHUK, ELK1, FOS, IKBKB, IKBKG, IRAK1, JUN, LY96, MAP2K3, MAP2K4, MAP2K6, MAP3K1, MAP3K14, MAP3K7, MAP3K7IP1, MAP3K7IP2, MAPK14, MAPK8, MYD88, NFKB1, NFKBIA, PGLYRP, PPARA, PRKR, RELA, SITPEC, TIRAP, TLR10, TLR2, TLR3, TLR4, TLR6, TLR7, TLR9, TOLLIP, TRAF6 | 31 | CD14(1), IKBKB(1), MAP2K3(1), MAP3K1(1), MAP3K7(1), MAPK8(1), MYD88(1), NFKB1(2), TLR4(3), TLR6(1), TLR7(3), TRAF6(1) | 2736100 | 17 | 14 | 17 | 2 | 3 | 3 | 7 | 3 | 1 | 0 | 0.17 | 0.023 | 1 |
8 | TOB1PATHWAY | TGF-beta signaling activates SMADs, which interact with intracellular Tob to maintain unstimulated T cells by repressing IL-2 expression. | CD28, CD3D, CD3E, CD3G, CD3Z, IFNG, IL2, IL2RA, IL4, MADH3, MADH4, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TGFBR3, TOB1, TOB2, TRA@, TRB@ | 16 | TGFBR1(1), TGFBR3(2), TOB1(1), TOB2(1) | 796550 | 5 | 5 | 5 | 1 | 0 | 2 | 1 | 0 | 2 | 0 | 0.64 | 0.029 | 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 | 14 | ARPC2(1), ARPC3(1), CDC42(1), PDGFRA(1), PIK3CA(3) | 1004800 | 7 | 7 | 7 | 0 | 1 | 5 | 0 | 1 | 0 | 0 | 0.18 | 0.031 | 1 |
10 | RIBOFLAVIN_METABOLISM | ACP1, ACP2, ACP5, ACPP, ACPT, ENPP1, ENPP3, FLAD1, RFK, TYR | 10 | ACP1(1), ACP2(1), ENPP1(1), ENPP3(1), TYR(1) | 729400 | 5 | 5 | 5 | 1 | 0 | 1 | 1 | 1 | 2 | 0 | 0.6 | 0.032 | 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. ##REF##99
This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.