MutSig results for LUSC

Number of individuals: 135

Summary of findings

Significantly mutated genes (q≤0.1)278
Mutations seen in COSMIC0
Significantly mutated genes on COSMIC territory0
Genes with clustered mutations (≤3 aa apart)1
Significantly mutated genesets89
. . . . . . . . . (excluding sig.mutated genes)1

Mutation preprocessing

Read 150 MAFs of type "Broad"
Total number of mutations in input MAFs: 49189
After removing 5553 noncoding mutations: 43636
After collapsing adjacent/redundant mutations: 43634

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

Mutation filtering

Number of mutations before filtering:		43634
After removing 46 mutations outside patient set: 43588
After removing 87 mutations outside gene set: 43501
After removing 12445 mutations outside category set: 31056
After removing 21260 "impossible" mutations in
gene-patient-category bins of zero coverage: 9796

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)133131313390004<1.00e-11<7.86e-09
2ADAMTS12ADAM metallopeptidase with thrombospondin type 1 motif, 121350202019579310<1.00e-11<7.86e-09
3SLIT3slit homolog 3 (Drosophila)540868314111<1.00e-11<7.86e-09
4ADAM22ADAM metallopeptidase domain 22670888133110<1.00e-11<7.86e-09
5CNBD1cyclic nucleotide binding domain containing 1659666022002<1.00e-11<7.86e-09
6VWFvon Willebrand factor1517121212145012<1.00e-11<7.86e-09
7LRP1Blow density lipoprotein-related protein 1B (deleted in tumors)16534523952111626136<1.00e-11<7.86e-09
8COL22A1collagen, type XXII, alpha 15772161516437006<1.00e-11<7.86e-09
9SVEP1sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1418510810344101<1.00e-11<7.86e-09
10SPAG17sperm associated antigen 178370171317139203<1.00e-11<7.86e-09
11CSMD1CUB and Sushi multiple domains 1138662825287816022<1.00e-11<7.86e-09
12PAPPA2pappalysin 21197824202310814101<1.00e-11<7.86e-09
13CSMD3CUB and Sushi multiple domains 328648524352101523347<1.00e-11<7.86e-09
14MYH13myosin, heavy chain 13, skeletal muscle607511911225301<1.00e-11<7.86e-09
15C6complement component 66615111111123204<1.00e-11<7.86e-09
16RYR3ryanodine receptor 31606524232481110102<1.00e-11<7.86e-09
17LRP2low density lipoprotein-related protein 2176232219228711121<1.00e-11<7.86e-09
18SCN1Asodium channel, voltage-gated, type I, alpha subunit17275181318388002<1.00e-11<7.86e-09
19PCDH15protocadherin 15267292219226414013<1.00e-11<7.86e-09
20RYR2ryanodine receptor 2 (cardiac)75777603859141133727<1.00e-11<7.86e-09
21SPHKAPSPHK1 interactor, AKAP domain containing363022117213612102<1.00e-11<7.86e-09
24MUC16mucin 16, cell surface associated174250684168301737572<1.00e-11<7.86e-09
26GPR112G protein-coupled receptor 11295781111110520133.74e-112.71e-08
28SELPselectin P (granule membrane protein 140kDa, antigen CD62)9456661130021.14e-107.70e-08
29PPFIA2protein tyrosine phosphatase, receptor type, f polypeptide (PTPRF), interacting protein (liprin), alpha 21324440201011.28e-108.31e-08
30DNAH11dynein, axonemal, heavy chain 11233771616164390131.55e-109.72e-08

(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 "*Np(A/C/T)->nonflip"
n3 = number of nonsilent mutations of type "*NpG->nonflip"
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

1C20orf26chromosome 20 open reading frame 2610011
2DNAH8dynein, axonemal, heavy chain 826301
3ABCA13ATP-binding cassette, sub-family A (ABC1), member 1316801
4SCN5Asodium channel, voltage-gated, type V, alpha subunit61900
5GBF1golgi-specific brefeldin A resistance factor 142100
6CUBNcubilin (intrinsic factor-cobalamin receptor)183000
7PKHD1L1polycystic kidney and hepatic disease 1 (autosomal recessive)-like 1298400
8CELSR3cadherin, EGF LAG seven-pass G-type receptor 3 (flamingo homolog, Drosophila)616100
9MXRA5matrix-remodelling associated 51068600
10GPR98G protein-coupled receptor 982385000
11SYNE1spectrin repeat containing, nuclear envelope 12785100
12A2ML1alpha-2-macroglobulin-like 14Inf00
13AACSacetoacetyl-CoA synthetase2Inf00
14AAK1AP2 associated kinase 14Inf00
15AARS2alanyl-tRNA synthetase 2, mitochondrial (putative)4Inf00
16ABCA10ATP-binding cassette, sub-family A (ABC1), member 104Inf00
17ABCA4ATP-binding cassette, sub-family A (ABC1), member 48Inf00
18ABCA6ATP-binding cassette, sub-family A (ABC1), member 65Inf00
19ABCB1ATP-binding cassette, sub-family B (MDR/TAP), member 19Inf00
20ABCB5ATP-binding cassette, sub-family B (MDR/TAP), member 54Inf00
21ABCC1ATP-binding cassette, sub-family C (CFTR/MRP), member 14Inf00
22ABCC12ATP-binding cassette, sub-family C (CFTR/MRP), member 129Inf00
23ABCC2ATP-binding cassette, sub-family C (CFTR/MRP), member 22Inf00
24ABCC8ATP-binding cassette, sub-family C (CFTR/MRP), member 86Inf00
25ABCC9ATP-binding cassette, sub-family C (CFTR/MRP), member 95Inf00
26ABCF2ATP-binding cassette, sub-family F (GCN20), member 22Inf00
27ABCF3ATP-binding cassette, sub-family F (GCN20), member 32Inf00
28ABCG8ATP-binding cassette, sub-family G (WHITE), member 8 (sterolin 2)5Inf00
29ABLIM1actin binding LIM protein 12Inf00
30ABLIM3actin binding LIM protein family, member 32Inf00

(click for full table with 2620 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

1GPCRDB_CLASS_B_SECRETIN_ LIKE20CALCR(2), CRHR1(3), CRHR2(1), ELTD1(9), EMR1(5), EMR2(3), GLP2R(2), GPR64(3)700352822287613144<1.00e-11<7.70e-10
2STRIATED_MUSCLE_ CONTRACTION37ACTN3(2), DMD(10), MYBPC3(1), MYH6(8), MYH7(6), MYH8(14), MYOM1(2), NEB(9), TNNT3(1), TTN(173)823331226912256952114201921<1.00e-11<7.70e-10
3NO1PATHWAYShear stress in endothelial cells increases cytoplasmic calcium, which activates nitric oxide synthase III to release NO, which in turn regulates cardiac contractions.28CHRM1(1), CHRNA1(2), FLT4(1), NOS3(1), RYR2(60), SLC7A1(2)268724674166201238737<1.00e-11<7.70e-10
4HSA04720_LONG_TERM_ POTENTIATIONGenes involved in long-term potentiation67ADCY8(8), ARAF(1), BRAF(4), CACNA1C(14), CAMK2A(2), CAMK2D(1), CAMK4(1), CREBBP(10), EP300(4), GRIA1(5), GRIN2B(11), GRM1(8), ITPR1(1), ITPR2(5), ITPR3(3), KRAS(2), MAPK1(1), MAPK3(1), PLCB1(6), PLCB4(3), PPP3CC(1), PRKCA(3), RAF1(1), RPS6KA2(2)46118798579827293941016<1.00e-11<7.70e-10
5HSA04730_LONG_TERM_ DEPRESSIONGenes involved in long-term depression74ARAF(1), BRAF(4), CACNA1A(6), CRHR1(3), GNAS(2), GRIA1(5), GRM1(8), GUCY2C(3), GUCY2D(1), ITPR1(1), ITPR2(5), ITPR3(3), KRAS(2), LYN(1), MAPK1(1), MAPK3(1), NOS3(1), PLA2G4A(4), PLCB1(6), PLCB4(3), PPP2R2A(1), PRKCA(3), RAF1(1), RYR1(23)55161889538925155031011<1.00e-11<7.70e-10
6HSA04020_CALCIUM_ SIGNALING_PATHWAYGenes involved in calcium signaling pathway169ADCY2(11), ADCY3(3), ADCY4(3), ADCY8(8), ATP2A3(2), ATP2B1(4), ATP2B2(4), ATP2B4(1), CACNA1A(6), CACNA1C(14), CACNA1D(1), CACNA1E(14), CACNA1F(3), CACNA1G(4), CACNA1H(1), CACNA1I(7), CAMK2A(2), CAMK2D(1), CAMK4(1), CHRM1(1), EGFR(2), ERBB3(2), GNAL(1), GNAS(2), GRM1(8), ITPR1(1), ITPR2(5), ITPR3(3), MYLK(1), NOS3(1), P2RX4(1), PDE1A(2), PDGFRB(5), PHKG1(1), PHKG2(1), PLCB1(6), PLCB4(3), PLCE1(6), PPP3CC(1), PRKCA(3), RYR1(23), RYR2(60), RYR3(24), SLC8A3(5), TBXA2R(1)1662500259922587360141151825<1.00e-11<7.70e-10
7SMOOTH_MUSCLE_CONTRACTION138ADCY2(11), ADCY3(3), ADCY4(3), ADCY5(2), ADCY8(8), ATP2A3(2), CAMK2A(2), CAMK2D(1), CREB3(1), CRHR1(3), GRK4(1), IL1B(1), ITPR1(1), ITPR2(5), ITPR3(3), NOS3(1), PRKCA(3), PRKCE(2), PRKCZ(1), RGS6(3), RYR1(23), RYR2(60), RYR3(24), TNXB(12), USP5(1)115989517777176525189111115<1.00e-11<7.70e-10
8CALCIUM_REGULATION_ IN_CARDIAC_CELLS139ADCY2(11), ADCY3(3), ADCY4(3), ADCY5(2), ADCY8(8), ATP1B2(1), ATP2A3(2), ATP2B1(4), ATP2B2(4), CACNA1A(6), CACNA1C(14), CACNA1D(1), CACNA1E(14), CAMK2A(2), CAMK2D(1), CAMK4(1), CHRM1(1), GJB1(1), GRK4(1), ITPR1(1), ITPR2(5), ITPR3(3), PEA15(1), PRKCA(3), PRKCE(2), PRKCZ(1), RGS6(3), RYR1(23), RYR2(60), RYR3(24), SLC8A3(5), USP5(1)1466343212882115859109111320<1.00e-11<7.70e-10
9HSA04512_ECM_RECEPTOR_ INTERACTIONGenes involved in ECM-receptor interaction87AGRN(1), CD36(1), CHAD(1), COL11A2(6), COL1A1(4), COL4A1(6), COL4A4(6), COL4A6(2), COL5A3(7), FNDC3A(1), GP1BA(3), GP5(3), HSPG2(4), ITGA1(1), ITGA2(5), ITGA5(1), ITGA7(2), ITGA8(8), ITGB4(2), ITGB6(1), LAMA1(7), LAMA2(10), LAMA3(6), LAMA5(5), LAMB1(5), LAMB2(3), LAMB4(3), RELN(27), TNC(5), TNXB(12), VWF(12)136513216078160514877512181.60e-101.10e-08
10LAIRPATHWAYThe local acute inflammatory response is mediated by activated macrophages and mast cells or by complement activation.16C3(1), C6(11), C7(4), ITGAL(2), SELP(6)7449424232485103066.75e-104.16e-08

(click for full table with 616 genesets)

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

Significantly mutated genesets (excluding significantly mutated genes)

1GPCRDB_CLASS_B_SECRETIN_ LIKE19CALCR(2), CRHR1(3), CRHR2(1), EMR1(5), EMR2(3), GLP2R(2), GPR64(3)6305019171975101212.17e-060.0013
3ST_MYOCYTE_AD_PATHWAYCardiac myocytes have a variety of adrenergic receptors that induce subtype-specific signaling effects.22APC(7), EPHB2(3), ITPR1(1), ITPR2(5), ITPR3(3), KCNJ9(3), MAPK1(1), RHO(1)14520924222435112240.000690.12
4HSA04664_FC_EPSILON_ RI_SIGNALING_PATHWAYGenes involved in Fc epsilon RI signaling pathway72BTK(2), IL4(1), INPP5D(4), LYN(1), MAP2K6(2), MAPK1(1), MAPK3(1), MS4A2(1), PIK3R5(4), PLA2G4A(4), PRKCA(3), PRKCE(2), RAF1(1), SOS1(3)20736330253076170340.000790.12
5HSA00950_ALKALOID_ BIOSYNTHESIS_IGenes involved in alkaloid biosynthesis I5DDC(3), TAT(3)132326661240000.00110.14
6IL12PATHWAYIL12 and Stat4 Dependent Signaling Pathway in Th1 Development20CD3E(1), CXCR3(1), IL12RB2(2), JAK2(3), MAP2K6(2)406239892140130.00150.15
7TRKAPATHWAYNerve growth factor (NGF) promotes neuronal survival and proliferation by binding its receptor TrkA, which activates PI3K/AKT, Ras, and the MAP kinase pathway.12NTRK1(5), PRKCA(3), SOS1(3)618621111111070220.00200.18
8GLYCOLYSISPATHWAYGlycolysis is an evolutionarily conserved pathway by which one glucose molecule is converted to two pyruvate molecules for a gain of 2 ATP.9GPI(3), HK1(3), PGK1(2)375078780520010.00230.18
9TPOPATHWAYThrombopoietin binds to its receptor and activates cell growth through the Erk and JNK MAP kinase pathways, protein kinase C, and JAK/STAT activation.22JAK2(3), MAPK3(1), PRKCA(3), RAF1(1), RASA1(2), SOS1(3), STAT1(1), STAT5B(1)1089481515151180240.00300.21
10ST_INTERLEUKIN_4_ PATHWAYLike IL-13, IL-4 is produced by Th2 cells on activation of the T cell antigen receptor, and by mast and basophil cells on activation of the IgE receptor.26IL4(1), INPP5D(4), JAK2(3), SOS1(3)568001111110170210.00420.25

(click for full table with 616 genesets)

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