This pipeline maps genes, with mutation or copy number alteration AND this alteration is highly correlated with mRNA expression, to pathways curated in the KEGG and BIOCARTA databases. It identifies pathways significantly enriched with these genes. The pipeline also identifies pathways significantly enriched with marker genes of each expression subtype of cancer.
genes with mutation: identified by the Mutation_Significance pipeline
genes with copy number alteration: identified by the CopyNumber_Gistic2 pipeline
correlation between copy number and mRNA expression: identified by the Correlate_CopyNumber_vs_mRNA pipeline
marker genes and expression subtypes: identified by the mRNAConsensusClustering pipeline
There are 22 genes with significant mutation (Q value <= 0.1) and 574 genes with significant copy number alteration (Q value <= 0.25). The identified marker genes (Q value <= 0.01 or within top 2000) are 1960 for subtype 1, 1960 for subtype 2, 1960 for subtype 3, 1960 for subtype 4. Pathways significantly enriched with these genes (Q value <= 0.01) are identified :
27 pathways significantly enriched with genes with copy number alteration or mutation.
6 pathways significantly enriched with marker genes of gene expression subtype 1
1 pathways significantly enriched with marker genes of gene expression subtype 2
0 pathways significantly enriched with marker genes of gene expression subtype 3
3 pathways significantly enriched with marker genes of gene expression subtype 4
Table 1. Get Full Table Top Pathways enriched with genes with copy number alteration or mutation. Nof Genes : No. of genes in this pathway. Nof CNV_Mut : No. of genes with copy number alteration or mutation in this pathway. Enrichment , P value and Q value : See Methods & Data below. CNV_Mut Genes in Pathway: genes with copy number alteration or mutation in this pathway.
| Pathway | Nof Genes | Nof CNV_Mut | Enrichment | P value | Q value |
|---|---|---|---|---|---|
| KEGG_COLORECTAL_CANCER | 62 | 12 | 2.8 | 0 | 0 |
| KEGG_PROTEASOME | 48 | 9 | 2.8 | 0 | 0.0003 |
| KEGG_PANCREATIC_CANCER | 70 | 11 | 2.5 | 0 | 0.0003 |
| KEGG_ENDOMETRIAL_CANCER | 52 | 10 | 2.8 | 0 | 0.0003 |
| BIOCARTA_PROTEASOME_PATHWAY | 19 | 6 | 3.5 | 0 | 0.0007 |
CASP3,PIK3CA,BRAF,TP53,TCF7L2,KRAS,RAC1,APC,SMAD4,SMAD3,RAF1,SMAD2
PSMA7,PSMB5,PSMF1,PSMD4,PSMC6,PSMA6,PSMD12,PSMC1,PSMA3
PIK3CA,BRAF,TP53,ERBB2,BCL2L1,KRAS,RAC1,SMAD4,RAF1,SMAD3,SMAD2
PTEN,PIK3CA,BRAF,TP53,ERBB2,TCF7L2,KRAS,APC,RAF1,NRAS
UBE3A,PSMA7,PSMB5,PSMA6,PSMA3,RPN2
Table 2. Get Full Table Top Pathways enriched with marker genes of gene expression subtype 1 . Nof Genes : No. of genes in this pathway. Nof Marker : No. of marker genes of gene expression subtype 1 in this pathway. Enrichment , P value and Q value : See Methods & Data below. Marker Gene in Pathway: markers of gene expression subtype 1 in this pathway
| Pathway | Nof Genes | Nof Marker | Enrichment | P value | Q value |
|---|---|---|---|---|---|
| KEGG_CYTOKINE_CYTOKINE_RECEPTOR_INTERACTION | 267 | 49 | 1.1 | 0 | 0 |
| KEGG_CELL_ADHESION_MOLECULES_CAMS | 134 | 30 | 1.4 | 0 | 0 |
| KEGG_ALLOGRAFT_REJECTION | 38 | 12 | 2 | 0 | 0.0017 |
| KEGG_TYPE_I_DIABETES_MELLITUS | 44 | 12 | 1.8 | 0.0001 | 0.0077 |
| KEGG_HEMATOPOIETIC_CELL_LINEAGE | 88 | 18 | 1.3 | 0.0002 | 0.0096 |
VEGFB,CCR7,CCR5,CCR3,CCR2,PDGFRA,PF4V1,LIF,IL17A,IFNA1,KDR,INHBB,TNFRSF10D,IL12A,CXCL9,CXCL6,ENC1,IL10RB,CCL21,IL7,CCL15,CCL17,CCL13,CXCL10,TNFRSF17,IL22,CCL2,IL22RA1,CCL8,CCL4,CXCL13,IL22RA2,FASLG,IL8RB,CXCR6,LTB,IL18RAP,EDAR,OSM,AMH,TNF,CTF1,KITLG,EPO,AMHR2,IL2RA,FLT3,PRLR,EPOR
NRCAM,HLA-F,MADCAM1,HLA-DRA,GLG1,CTLA4,PVRL2,HLA-DPB1,HLA-DOB,ITGA4,ITGA6,CLDN8,CD8A,CLDN5,SDC4,HLA-DMA,ICAM3,CD86,CD80,CLDN1,CNTN1,JAM2,CLDN19,CDH4,VCAM1,CD6,CD28,PTPRC,SELP,SELL
TNF,FASLG,HLA-DMA,HLA-DPB1,HLA-DOB,CD28,GZMB,HLA-F,CD86,CD80,IL12A,HLA-DRA
TNF,FASLG,HLA-DMA,HLA-DPB1,HLA-DOB,CD28,GZMB,HLA-F,CD86,CD80,IL12A,HLA-DRA
CD8A,CD3D,CD38,HLA-DRA,TNF,KITLG,CD9,FCGR1A,EPO,IL2RA,IL7,FLT3,CD1C,ITGA4,CD19,ITGA6,EPOR,CD14
Table 3. Get Full Table Top Pathways enriched with marker genes of gene expression subtype 2 . Nof Genes : No. of genes in this pathway. Nof Marker : No. of marker genes of gene expression subtype 2 in this pathway. Enrichment , P value and Q value : See Methods & Data below. Marker Gene in Pathway: markers of gene expression subtype 2 in this pathway
| Pathway | Nof Genes | Nof Marker | Enrichment | P value | Q value |
|---|---|---|---|---|---|
| KEGG_PATHWAYS_IN_CANCER | 328 | 60 | 1 | 0 | 0 |
| BIOCARTA_PPARA_PATHWAY | 58 | 14 | 1.5 | 0.0003 | 0.023 |
| KEGG_CYTOKINE_CYTOKINE_RECEPTOR_INTERACTION | 267 | 40 | 0.77 | 0.0004 | 0.023 |
| KEGG_CELL_ADHESION_MOLECULES_CAMS | 134 | 24 | 1 | 0.0004 | 0.023 |
| KEGG_LEISHMANIA_INFECTION | 72 | 16 | 1.4 | 0.0003 | 0.023 |
PTGS2,PGF,PIK3CG,WNT10B,CTNNA1,MECOM,VEGFB,BMP4,TCF7,HGF,LAMA1,LAMA4,NTRK1,FGF7,MLH1,NFKB1,NFKB2,GLI1,FLT3LG,NOS2,FGF1,AKR1B1,TP53,WNT9B,IL6,FZD2,STAT1,BIRC2,FZD7,WNT7B,RASSF5,TCEB1,PDGFB,PDGFA,MMP9,FOXO1,FGF12,MMP1,TGFB1,TGFB2,WNT4,CDKN2A,CDKN2B,CSF3R,FGF20,HIF1A,TRAF1,FGFR3,TRAF5,AXIN1,ITGA6,E2F3,CASP8,RUNX1T1,DAPK1,CKS1B,CEBPA,COL4A4,MSH3,COL4A6
ACOX1,PPARA,PTGS2,PDGFA,EHHADH,CITED2,PRKAR2B,PRKAR2A,NOS2,PIK3CG,CD36,SOX9,FABP1,NCOR1
VEGFB,CCR2,IL1R1,IL17B,HGF,FLT3LG,TNFRSF10A,TNFRSF10B,CCL26,CCL23,CCL21,IL10RA,IL6,CCL13,CCL14,PDGFB,PDGFA,TNFSF15,TNFSF12,TGFB1,TGFB2,CSF3R,IL24,IL22,CCL3,CCL8,IL12RB2,XCL1,XCL2,IL21R,CXCR4,OSM,NGFR,TNFRSF8,TNFRSF18,EPO,FLT1,LEP,PRLR,EPOR
CADM1,F11R,PTPRM,PTPRF,PHOX2A,HLA-DPA1,HLA-DRA,ITGAM,ITGA6,ITGA8,NLGN4X,CLDN6,SDC4,HLA-DMB,HLA-DMA,CD86,SDC1,CLDN2,CLDN18,VCAM1,PTPRC,SELL,NLGN1,SELE
PTGS2,TLR2,NFKB1,HLA-DMB,HLA-DMA,TGFB1,TGFB2,NOS2,FCGR3A,NCF1,HLA-DPA1,HLA-DRA,C3,ITGAM,MAPK11,STAT1
Table 4. Get Full Table Top Pathways enriched with marker genes of gene expression subtype 3 . Nof Genes : No. of genes in this pathway. Nof Marker : No. of marker genes of gene expression subtype 3 in this pathway. Enrichment , P value and Q value : See Methods & Data below. Marker Gene in Pathway: markers of gene expression subtype 3 in this pathway
| Pathway | Nof Genes | Nof Marker | Enrichment | P value | Q value |
|---|---|---|---|---|---|
| KEGG_GAP_JUNCTION | 90 | 20 | 1.4 | 0.0001 | 0.015 |
| KEGG_ANTIGEN_PROCESSING_AND_PRESENTATION | 89 | 18 | 1.4 | 0.0001 | 0.02 |
| KEGG_CELL_ADHESION_MOLECULES_CAMS | 134 | 24 | 1.1 | 0.0003 | 0.03 |
| BIOCARTA_NO2IL12_PATHWAY | 17 | 6 | 2 | 0.0023 | 0.084 |
| KEGG_LYSOSOME | 121 | 21 | 0.98 | 0.0016 | 0.084 |
ADCY3,ADCY4,PDGFB,ADCY7,ADCY5,GUCY1A3,PRKACB,RP11-631M21.2,PLCB1,PLCB2,TUBA1C,TUBB3,PRKCG,ADRB1,GUCY1B3,GNAI3,KRAS,ITPR1,TJP1,HTR2A
PDIA3,RFXANK,B2M,LTA,HLA-C,HLA-E,HLA-DQA1,HLA-G,HLA-F,KIR2DL1,KIR2DL2,HLA-DQB1,TAP1,HSPA4,CD4,HSPA5,HSPA8,KIR2DS4
PVR,HLA-C,CD40,HLA-E,HLA-G,HLA-DQA1,HLA-F,CD34,GLG1,ALCAM,PVRL3,CTLA4,ITGA4,ITGA9,JAM2,HLA-DQB1,CDH5,VCAM1,CD2,CD4,SELP,NLGN2,CLDN23,CDH15
CD247,IL12RB2,IL12RB1,IL12A,CD2,CD4
NPC2,PPT2,CTSA,SLC11A2,NAGA,SCARB2,LAPTM4B,CLTB,ASAH1,GLB1,ATP6V0D2,CLN3,HYAL1,CTSK,SORT1,CTSC,CTSG,AP4S1,MANBA,ARSA,GGA3
Table 5. Get Full Table Top Pathways enriched with marker genes of gene expression subtype 4 . Nof Genes : No. of genes in this pathway. Nof Marker : No. of marker genes of gene expression subtype 4 in this pathway. Enrichment , P value and Q value : See Methods & Data below. Marker Gene in Pathway: markers of gene expression subtype 4 in this pathway
| Pathway | Nof Genes | Nof Marker | Enrichment | P value | Q value |
|---|---|---|---|---|---|
| KEGG_VASOPRESSIN_REGULATED_WATER_REABSORPTION | 44 | 14 | 1.8 | 0 | 0.002 |
| BIOCARTA_INTEGRIN_PATHWAY | 38 | 12 | 1.8 | 0.0001 | 0.0045 |
| KEGG_CALCIUM_SIGNALING_PATHWAY | 178 | 31 | 0.98 | 0.0001 | 0.0066 |
| BIOCARTA_ECM_PATHWAY | 24 | 8 | 1.9 | 0.0007 | 0.02 |
| BIOCARTA_MCALPAIN_PATHWAY | 25 | 8 | 1.8 | 0.001 | 0.02 |
ADCY3,RAB5B,AQP2,DYNLL1,DYNC2H1,RAB11B,RAB11A,CREB3L3,ARHGDIA,ARHGDIB,AVP,CREB1,DCTN2,GNAS
TLN1,ZYX,CSK,CAPNS1,MAP2K1,ITGA1,ACTN2,ACTN3,CAPN1,FYN,MAPK3,RAP1A
SLC8A3,ADCY3,ATP2B2,HTR4,RYR3,RYR1,RYR2,BDKRB2,ADRB3,GRIN1,SPHK1,P2RX1,PLCG1,LTB4R2,PLCG2,ADRA1B,MYLK,TACR3,PLCB2,PHKG1,GNAS,PPP3R1,DHX8,PDE1C,PPP3CB,PLCD4,CALML6,CAMK2B,SLC8A1,ITPR1,HTR2C
TLN1,MAP2K1,MYL2,ITGA1,ARHGAP5,FYN,MAPK3,MYLK
TLN1,MYL2,CAPNS1,ITGA1,CAPN2,CAPN1,MAPK3,MYLK
Let genes with copy number alteration or mutation be query genes. Let marker genes of specific identified subtypes be query genes. The Enrichment is calculated as:
-
Enrichment = log2 (# of query genes in the pathway/# No of query genes) - log2 (# of genes in the pathway/# of human genes)
The statistical signficance of the pathways that are enriched with genes with copy number alteration or mutation, and the pathways that are enriched with markers genes of specific identified subtypes is measured by P value.
-
P value = Fisher exact P value
The Q value is for adjusting P value for multiple testing. A public available R package is used to calculate the Q value.
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.