MutSig results for LUAD

Number of individuals: 120

Summary of findings

Significantly mutated genes (q≤0.1)193
Mutations seen in COSMIC0
Significantly mutated genes on COSMIC territory0
Genes with clustered mutations (≤3 aa apart)1
Significantly mutated genesets107
. . . . . . . . . (excluding sig.mutated genes)33

Mutation preprocessing

Read 122 MAFs of type "Broad"
Total number of mutations in input MAFs: 36215
After removing 3656 noncoding mutations: 32559
After collapsing adjacent/redundant mutations: 32554

Please see MutSigPreprocess "stdout.txt" for full details.

Mutation filtering

Number of mutations before filtering:		32554
After removing 56 mutations outside gene set: 32498
After removing 9237 mutations outside category set: 23261
After removing 16119 "impossible" mutations in
gene-patient-category bins of zero coverage: 7142

Please see MutSigRun "stdout.txt" for full details.

Final mutation list

Final set of mutations used in analysis

Mutation breakdown by type


Nonsilent mutations: categories and mutation rates


Target coverage for each individual

(click for higher-resolution version)

Mutation counts, total coverage, and mutation rates for each individual

(click for higher-resolution version)
(click for tabular version)

Significantly mutated genes

1USH2AUsher syndrome 2A (autosomal recessive, mild)120131313370501<1.00e-11<9.93e-09
2ADAMTS12ADAM metallopeptidase with thrombospondin type 1 motif, 1212001716173410102<1.00e-11<9.93e-09
3SLIT3slit homolog 3 (Drosophila)4806661022011<1.00e-11<9.93e-09
4FRAS1Fraser syndrome 11200121012161311<1.00e-11<9.93e-09
5LRP1Blow density lipoprotein-related protein 1B (deleted in tumors)14760453145814161005<1.00e-11<9.93e-09
6PTPRDprotein tyrosine phosphatase, receptor type, D6960171417448113<1.00e-11<9.93e-09
7SVEP1sushi, von Willebrand factor type A, EGF and pentraxin domain containing 13720888231103<1.00e-11<9.93e-09
8GPR112G protein-coupled receptor 1128520171617645422<1.00e-11<9.93e-09
9CSMD1CUB and Sushi multiple domains 11259224192411513303<1.00e-11<9.93e-09
10NOTCH4Notch homolog 4 (Drosophila)539610910126200<1.00e-11<9.93e-09
11ABCB5ATP-binding cassette, sub-family B (MDR/TAP), member 56722111111333302<1.00e-11<9.93e-09
12CSMD3CUB and Sushi multiple domains 32574539253811169914<1.00e-11<9.93e-09
13LAMA2laminin, alpha 2 (merosin, congenital muscular dystrophy)10440151415683301<1.00e-11<9.93e-09
14PAPPA2pappalysin 210680121012345300<1.00e-11<9.93e-09
15RYR3ryanodine receptor 314280151415646401<1.00e-11<9.93e-09
16KEAP1kelch-like ECH-associated protein 1186521818170113112<1.00e-11<9.93e-09
17RYR2ryanodine receptor 2 (cardiac)674544436441110161224<1.00e-11<9.93e-09
18MUC16mucin 16, cell surface associated1534875442531210251045<1.00e-11<9.93e-09
20PCDH15protocadherin 15237601513157631231.19e-111.12e-08
21CACNA1Ecalcium channel, voltage-dependent, R type, alpha 1E subunit405791916194556123.31e-112.97e-08
22FLT4fms-related tyrosine kinase 44545550112105.48e-114.70e-08
23SPTBN4spectrin, beta, non-erythrocytic 41294441300017.03e-115.77e-08
24VWFvon Willebrand factor14696662031208.09e-116.36e-08
25DMDdystrophin (muscular dystrophy, Duchenne and Becker types)20160129124360217.16e-105.40e-07
26SDK1sidekick homolog 1, cell adhesion molecule (chicken)17536564051008.93e-106.48e-07
27STXBP5Lsyntaxin binding protein 5-like50408881322101.78e-091.24e-06
28PTPRBprotein tyrosine phosphatase, receptor type, B56048882232016.09e-094.08e-06
29BIRC6baculoviral IAP repeat-containing 6 (apollon)156631110110461006.28e-094.08e-06
30MYH13myosin, heavy chain 13, skeletal muscle54007775402106.49e-094.08e-06

(click for full table with 18865 genes)

N = number of sequenced bases in this gene across the individual set
n = 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 nonsilent mutation
nsil = number of silent mutations in this gene across the individual set
n1 = number of nonsilent mutations of type "A->T"
n2 = number of nonsilent mutations of type "C->(A/T)"
n3 = number of nonsilent mutations of type "A->(C/G)"
n4 = number of nonsilent mutations of type "C->G"
n5 = number of nonsilent mutations of type "indel+null"
null = mutation category that includes nonsense, frameshift, splice-site mutations
p_classic = p-value for the observed amount of nonsilent mutations being elevated in this gene
p_ns_s = p-value for the observed nonsilent/silent ratio being elevated in this gene
p = p-value (overall)
q = q-value, False Discovery Rate (Benjamini-Hochberg procedure)

COSMIC analyses

Two distinct analyses are reported using the COSMIC database:
(COS1) COSMIC used as a filter to increase power by restricting the territory of each gene
(COS2) COSMIC used as a prior for the importance of a gene

(COS1) Significantly mutated genes (COSMIC territory only)


(click for full table with 4550 genes)

n = number of mutations in this gene in 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 × 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)

(COS2) Genes mutated at sites that are highly reported in COSMIC


(click for full table with 4550 genes)

n = number of mutations in this gene in the individual set
cos = number of unique mutated sites in this gene in COSMIC
n_cos = overlap between n and cos
cos_ev = total evidence: number of reports in COSMIC for mutations seen in this gene

Mutations reported in COSMIC


(click for full table with 0 mutations)

Genes with clustered mutations

1MUC2mucin 2, oligomeric mucus/gel-forming5211
2GRIN2Bglutamate receptor, ionotropic, N-methyl D-aspartate 2B8901
3PKHD1L1polycystic kidney and hepatic disease 1 (autosomal recessive)-like 11911600
4MXRA5matrix-remodelling associated 5971600
5SH3TC2SH3 domain and tetratricopeptide repeats 2591300
6MDN1MDN1, midasin homolog (yeast)492700
7PDCD11programmed cell death 114140100
8GPR98G protein-coupled receptor 989144500
9A2ML1alpha-2-macroglobulin-like 13Inf00
10AAK1AP2 associated kinase 14Inf00
11AARS2alanyl-tRNA synthetase 2, mitochondrial (putative)2Inf00
12ABCA10ATP-binding cassette, sub-family A (ABC1), member 104Inf00
13ABCA13ATP-binding cassette, sub-family A (ABC1), member 1314Inf00
14ABCA3ATP-binding cassette, sub-family A (ABC1), member 34Inf00
15ABCA4ATP-binding cassette, sub-family A (ABC1), member 43Inf00
16ABCA6ATP-binding cassette, sub-family A (ABC1), member 63Inf00
17ABCA7ATP-binding cassette, sub-family A (ABC1), member 72Inf00
18ABCB1ATP-binding cassette, sub-family B (MDR/TAP), member 13Inf00
19ABCB5ATP-binding cassette, sub-family B (MDR/TAP), member 511Inf00
20ABCC12ATP-binding cassette, sub-family C (CFTR/MRP), member 125Inf00
21ABCC3ATP-binding cassette, sub-family C (CFTR/MRP), member 33Inf00
22ABCC5ATP-binding cassette, sub-family C (CFTR/MRP), member 52Inf00
23ABCC8ATP-binding cassette, sub-family C (CFTR/MRP), member 85Inf00
24ABCC9ATP-binding cassette, sub-family C (CFTR/MRP), member 95Inf00
25ABCG4ATP-binding cassette, sub-family G (WHITE), member 42Inf00
26ABCG5ATP-binding cassette, sub-family G (WHITE), member 5 (sterolin 1)2Inf00
27ABLIM3actin binding LIM protein family, member 33Inf00
28ACACAacetyl-Coenzyme A carboxylase alpha2Inf00
29ACACBacetyl-Coenzyme A carboxylase beta4Inf00
30ACCN2amiloride-sensitive cation channel 2, neuronal2Inf00

(click for full table with 2257 genes)

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

Significantly mutated genesets

1ARENRF2PATHWAYNrf1 and nrf2 are transcription factors that bind to antioxidant response elements (AREs), promoters of genes involved in oxidative damage control.13CREB1(1), KEAP1(18), PRKCA(2)436412120201313122<1.00e-11<6.21e-10
2NO1PATHWAYShear stress in endothelial cells increases cytoplasmic calcium, which activates nitric oxide synthase III to release NO, which in turn regulates cardiac contractions.28CHRNA1(3), FLT4(5), NOS3(1), RYR2(44), SLC7A1(1)2395845438541113171455<1.00e-11<6.21e-10
3HSA04720_LONG_TERM_ POTENTIATIONGenes involved in long-term potentiation67ADCY8(7), ARAF(1), BRAF(4), CACNA1C(8), CAMK2A(1), CAMK2B(3), CAMK2D(1), CAMK4(3), CREBBP(2), GRIA1(3), GRIN2B(8), GRM1(8), ITPR1(2), ITPR2(6), ITPR3(4), KRAS(5), PLCB1(5), PLCB4(3), PPP3CC(1), PRKCA(2), RPS6KA2(1)40140278507525252415311<1.00e-11<6.21e-10
4STRIATED_MUSCLE_ CONTRACTION37ACTN3(2), DMD(12), MYBPC2(1), MYBPC3(3), MYH6(7), MYH7(5), MYH8(10), MYOM1(2), NEB(10), TPM2(1), TPM4(1), TTN(83)73405013766137423749281112<1.00e-11<6.21e-10
5HSA04020_CALCIUM_ SIGNALING_PATHWAYGenes involved in calcium signaling pathway169ADCY2(4), ADCY3(1), ADCY4(1), ADCY8(7), ATP2A3(1), ATP2B1(1), ATP2B2(4), ATP2B4(1), CACNA1A(1), CACNA1C(8), CACNA1D(6), CACNA1E(19), CACNA1F(2), CACNA1G(4), CACNA1H(1), CACNA1I(1), CAMK2A(1), CAMK2B(3), CAMK2D(1), CAMK4(3), EGFR(7), GNA11(1), GNAS(3), GRM1(8), ITPR1(2), ITPR2(6), ITPR3(4), MYLK(4), NOS3(1), PDE1A(1), PDE1B(1), PDGFRB(3), PLCB1(5), PLCB4(3), PLCD1(1), PLCD4(2), PLCE1(2), PPP3CC(1), PRKCA(2), PTK2B(2), RYR1(17), RYR2(44), RYR3(15), SLC8A2(1), SLC8A3(4)144603021081208665272521024<1.00e-11<6.21e-10
6HSA04912_GNRH_SIGNALING_ PATHWAYGenes involved in GnRH signaling pathway95ADCY2(4), ADCY3(1), ADCY4(1), ADCY5(4), ADCY8(7), CACNA1C(8), CACNA1D(6), CACNA1F(2), CAMK2A(1), CAMK2B(3), CAMK2D(1), EGFR(7), GNA11(1), GNAS(3), ITPR1(2), ITPR2(6), ITPR3(4), KRAS(5), MAP2K4(1), MAP2K6(1), PLA2G4A(3), PLCB1(5), PLCB4(3), PRKCA(2), PTK2B(2), SOS1(3)60689386538134202322615<1.00e-11<6.21e-10
7CALCIUM_REGULATION_ IN_CARDIAC_CELLS139ADCY2(4), ADCY3(1), ADCY4(1), ADCY5(4), ADCY8(7), ATP2A3(1), ATP2B1(1), ATP2B2(4), CACNA1A(1), CACNA1C(8), CACNA1D(6), CACNA1E(19), CAMK2A(1), CAMK2B(3), CAMK2D(1), CAMK4(3), GJB1(1), GNA11(1), GRK4(2), GRK6(1), ITPR1(2), ITPR2(6), ITPR3(4), PRKCA(2), PRKCE(1), RYR1(17), RYR2(44), RYR3(15), SLC8A3(4)12809021657016558385841721<1.00e-11<6.21e-10
8HSA04512_ECM_RECEPTOR_ INTERACTIONGenes involved in ECM-receptor interaction87AGRN(1), CD36(1), COL11A2(2), COL4A1(2), COL4A4(5), COL4A6(8), COL5A3(5), FNDC3A(2), GP1BA(1), GP5(1), HSPG2(5), ITGA1(1), ITGA11(2), ITGA2(3), ITGA5(1), ITGA7(1), ITGA8(6), ITGB4(1), LAMA1(11), LAMA2(15), LAMA3(5), LAMA5(3), LAMB1(4), LAMB2(8), LAMB3(3), LAMB4(8), LAMC3(3), RELN(16), TNC(12), TNXB(5), VWF(6)120330714758147433272171214<1.00e-11<6.21e-10
9SMOOTH_MUSCLE_CONTRACTION138ADCY2(4), ADCY3(1), ADCY4(1), ADCY5(4), ADCY8(7), ATP2A3(1), CAMK2A(1), CAMK2B(3), CAMK2D(1), CNN1(1), GRK4(2), GRK6(1), ITPR1(2), ITPR2(6), ITPR3(4), NOS3(1), PLCD1(1), PRKCA(2), PRKCE(1), RYR1(17), RYR2(44), RYR3(15), TNXB(5)10262571256212546284526917<1.00e-11<6.21e-10
10HSA04540_GAP_JUNCTIONGenes involved in gap junction92ADCY2(4), ADCY3(1), ADCY4(1), ADCY5(4), ADCY8(7), EGFR(7), GNA11(1), GNAS(3), GRM1(8), GUCY2C(3), ITPR1(2), ITPR2(6), ITPR3(4), KRAS(5), PDGFRB(3), PLCB1(5), PLCB4(3), PRKCA(2), SOS1(3), TUBA4A(1), TUBB4(1)536396744969281916187141.11e-116.21e-10

(click for full table with 616 genesets)

Notes: (Please see notes under significantly mutated gene table)

Significantly mutated genesets (excluding significantly mutated genes)

1HSA02010_ABC_TRANSPORTERS_ GENERALGenes involved in ABC transporters - general42ABCA13(14), ABCA3(4), ABCA4(3), ABCA6(3), ABCA7(2), ABCB1(3), ABCC1(1), ABCC10(1), ABCC12(5), ABCC2(1), ABCC3(3), ABCC5(2), ABCC8(5), ABCC9(5), ABCG4(2), ABCG5(2), ABCG8(1), TAP2(1)51955258415812181811470.0000800.046
2MONOCYTEPATHWAYMonocytes are a class of immune phagocytes that can develop into macrophages and express LFA-1, CD44, and other surface signaling proteins.10ITGAL(6), ITGAM(3), SELE(3)64350129123521220.000220.046
3NEUTROPHILPATHWAYNeutrophils are phagocytotic leukocytes that destroy foreign cells with reactive oxygen species or enzymatic digestion and express CD11 and CD18.8ITGAL(6), ITGAM(3), SELE(3)64350129123521220.000220.046
4LAIRPATHWAYThe local acute inflammatory response is mediated by activated macrophages and mast cells or by complement activation.15C3(2), C6(2), C7(3), ITGAL(6)647911312133451210.000350.048
5HSA04670_LEUKOCYTE_ TRANSENDOTHELIAL_ MIGRATIONGenes involved in Leukocyte transendothelial migration110ACTN3(2), CDH5(1), CTNND1(3), CYBB(1), GRLF1(3), ITGAL(6), ITGAM(3), MYL7(1), PIK3R5(2), PRKCA(2), PTK2(2), PTK2B(2), RHOH(2)2907563023301012102510.000390.048
6HSA00680_METHANE_ METABOLISMGenes involved in methane metabolism10TPO(6)221276662040200.00110.074
7HSA00940_PHENYLPROPANOID_ BIOSYNTHESISGenes involved in phenylpropanoid biosynthesis7TPO(6)221276662040200.00110.074
8BLYMPHOCYTEPATHWAYB cells express the major histocompatibility complex (class II MHC), immunoglobulins, adhesion proteins, and other factors on their cell surface.10CR1(3), ITGAL(6), PTPRC(6)908091514151642120.00110.074
10AGPCRPATHWAYG-protein coupled receptors (GPCRs) transduce extracellular signals across the plasma membrane; attenuation occurs by signal molecule degradation or receptor-mediated endocytosis.11GNAS(3), PRKCA(2)177335553302000.00130.074

(click for full table with 616 genesets)

Notes: (Please see notes under significantly mutated gene table)