This pipeline maps genes with mutation, genes with copy number gain/loss AND this alteration is highly correlated with mRNA expression to pathways curated in the KEGG, BIOCARTA, and STKE databases. It identifies pathways significantly enriched with these genes.
This pipeline also maps marker genes of the identified subtypes of cancer to pathways and identifies pathways significantly enriched with markers genes of specific subtypes of cancer.
There are 5 pathways significantly enriched with genes with copy number gain/loss or mutation.
There are 5 pathways significantly enriched with marker genes of cancer subtype 1
There are 5 pathways significantly enriched with marker genes of cancer subtype 2
There are 5 pathways significantly enriched with marker genes of cancer subtype 3
Table 1. Get Full Table Top Pathways enriched with genes with copy number gain/loss or mutation. Nof_Genes : No. of genes in this pathway. Nof_cnvOrMut_Genes : No. of genes with copy number gain/loss or mutation in this pathway. Enrichment , p_value and q_value : See Methods & Data below. cnvOrMut_Genes: genes with copy number gain/loss or mutation in this pathway.
Pathway | Nof_Genes | Nof_CnvOrMutGenes | Enrichment | p_value | q_value | CnvOrMut_Genes |
KEGG_FOCAL_ADHESION | 201 | 11 | 2.06393403190352 | 6.78218335232762e-05 | 0.0134085930772973 | BRAF,ERBB2,ITGA11,LAMB4,LAMA1,LAMA3,SOS2,EGFR,RELN,TNC,COL4A6 |
KEGG_LONG_TERM_POTENTIATION | 70 | 7 | 2.91919893892251 | 3.6787902056953e-05 | 0.0134085930772973 | GRIN2B,PLCB1,BRAF,GRM1,KRAS,ITPR2,CACNA1C |
KEGG_GNRH_SIGNALING_PATHWAY | 101 | 8 | 2.59727084403515 | 5.21578274645203e-05 | 0.0134085930772973 | ADCY2,EGFR,KRAS,CACNA1C,PLCB1,MAP3K1,SOS2,ITPR2 |
ST_G_ALPHA_I_PATHWAY | 34 | 5 | 3.4755922874469 | 7.65112301129659e-05 | 0.0134085930772973 | SOS2,PLCB1,EGFR,BRAF,ITPR2 |
KEGG_ECM_RECEPTOR_INTERACTION | 84 | 7 | 2.65616453308872 | 0.000118925518603148 | 0.0166733577081613 | RELN,TNC,ITGA11,LAMB4,COL4A6,LAMA1,LAMA3 |
Table 2. Get Full Table Top Pathways enriched with marker genes of identified cancer subtype 1 . Nof_Genes : No. of genes in this pathway. Nof_MarkerGenes : No. of marker genes of cancer subtype 1 in this pathway. Enrichment , p_value and q_value : See Methods & Data below. Marker_Gene: markers of cancer subtype 1 in this pathway
Pathway | Nof_Genes | Nof_MarkerGenes | Enrichment | p_value | q_value | Marker_Genes |
REACTOME_CELL_CYCLE_MITOTIC | 304 | 41 | 1.2587004416364 | 1.26297237094202e-07 | 8.85343632030359e-05 | AURKA,CDCA8,ANAPC1,RFC4,ZWINT,NEK2,TK1,NUF2,ALMS1,CDC20,NDC80,CDT1,DYNLL1,BUB1,FEN1,PRKAR2B,RAD21,SGOL2,SOX2,SPC25,TUBB2A,PSMB6,GINS1,CASC5,CDKN1A,UBE2E1,E2F2,KIF2C,CDC45L,MCM8,RANBP2,BUB1B,MAPRE1,PSMB10,RPA1,CENPA,KIF18A,CENPF,SFI1,CDC25A,ORC3L |
KEGG_HEMATOPOIETIC_CELL_LINEAGE | 88 | 17 | 1.84422136893349 | 2.92307326415694e-06 | 0.00102453717908701 | CD44,CD3D,IL6R,HLA-DRA,CSF2,ITGB3,IL7R,CD1C,ITGA1,CD1B,ITGA2,CD1A,ITGA3,ITGA4,CD1E,CD59,EPOR |
REACTOME_MITOTIC_PROMETAPHASE | 92 | 17 | 1.71297683565523 | 1.06072303098536e-05 | 0.00247855614906913 | KIF2C,CDCA8,RAD21,RANBP2,SGOL2,ZWINT,BUB1B,MAPRE1,SPC25,CENPA,BUB1,NUF2,KIF18A,CASC5,CENPF,CDC20,NDC80 |
REACTOME_MITOTIC_M_M_G1_PHASES | 157 | 23 | 1.37801715762729 | 1.86569292307227e-05 | 0.00326962684768414 | CDCA8,RAD21,SGOL2,ZWINT,SPC25,PSMB6,NUF2,CASC5,NDC80,CDC20,E2F2,CDT1,KIF2C,MCM8,RANBP2,BUB1B,MAPRE1,PSMB10,CENPA,BUB1,KIF18A,CENPF,ORC3L |
KEGG_ECM_RECEPTOR_INTERACTION | 84 | 15 | 1.66364912329166 | 5.24275100700049e-05 | 0.00735033691181469 | CD47,CD44,TNC,ITGB3,COL6A3,COL6A2,COL6A1,TNN,ITGA1,ITGA2,ITGA3,ITGA4,COL4A6,ITGA9,LAMA3 |
Table 3. Get Full Table Top Pathways enriched with marker genes of identified cancer subtype 2 . Nof_Genes : No. of genes in this pathway. Nof_MarkerGenes : No. of marker genes of cancer subtype 2 in this pathway. Enrichment , p_value and q_value : See Methods & Data below. Marker_Gene: markers of cancer subtype 2 in this pathway
Pathway | Nof_Genes | Nof_MarkerGenes | Enrichment | p_value | q_value | Marker_Genes |
REACTOME_CELL_CYCLE_MITOTIC | 304 | 100 | 1.89126308980755 | 6.00074342261197e-33 | 4.20652113925099e-30 | AURKA,PTTG1,AURKB,PRIM1,CDCA8,INCENP,NUP37,SKP2,MBD1,ORC1L,RFC5,MAD2L1,RFC2,ZWINT,TUBA4A,CCDC99,TK1,FBXO5,SKA2,CDC20,NDC80,CDC27,DHFR,PCNA,CDT1,CCNE2,CCNE1,DYNLL1,TUBB3,CDC7,CDC6,DSN1,CCND3,RRM2,NUP107,DYNC1I2,POLA2,BUB3,CEP135,BIRC5,PSMD14,CCNB2,KIF20A,DBF4,KNTC1,PKMYT1,SGOL2,SGOL1,FGFR1OP,PSMA7,PSMB4,SPC25,TUBB2A,POLE2,PSMB3,ORC6L,ERCC6L,GINS1,GINS2,GINS4,CASC5,DNA2,PLK4,PSMC4,PSMC2,E2F1,KIF23,KIF2C,CDC45L,MCM8,MCM7,TUBA1A,KIF2A,CDC2,CDK6,NUP85,MCM2,UBE2C,MCM4,CDK2,MCM6,BUB1B,CKS1B,HAUS2,TYMS,TUBGCP6,ORC2L,CENPO,CENPN,CENPM,CENPQ,CENPP,KIF18A,CENPF,CENPE,CENPK,CDC25C,MLF1IP,CDC25A,CENPH |
REACTOME_MITOTIC_M_M_G1_PHASES | 157 | 55 | 1.98207337810944 | 3.93693078721536e-20 | 1.37989424091898e-17 | KNTC1,AURKB,CDCA8,INCENP,NUP37,SGOL2,SGOL1,ORC1L,MAD2L1,ZWINT,CCDC99,PSMA7,PSMB4,SPC25,PSMB3,ORC6L,FBXO5,SKA2,ERCC6L,CASC5,NDC80,CDC20,PSMC4,PSMC2,E2F1,KIF23,CDT1,KIF2C,MCM8,MCM7,KIF2A,CDC6,DSN1,NUP85,MCM2,MCM4,MCM6,BUB1B,NUP107,ORC2L,BUB3,CENPO,CENPN,CENPM,CENPQ,CENPP,KIF18A,CENPF,BIRC5,CENPE,CENPK,MLF1IP,CENPH,PSMD14,KIF20A |
REACTOME_MITOTIC_PROMETAPHASE | 92 | 35 | 2.10105547436436 | 1.41914222052169e-14 | 3.31606232195236e-12 | KNTC1,AURKB,KIF2C,CDCA8,INCENP,NUP37,KIF2A,DSN1,SGOL2,SGOL1,NUP85,MAD2L1,ZWINT,BUB1B,NUP107,CCDC99,SPC25,SKA2,BUB3,ERCC6L,CENPO,CENPN,CENPM,CENPQ,CENPP,KIF18A,CASC5,CENPF,CDC20,CENPE,BIRC5,NDC80,CENPK,MLF1IP,CENPH |
REACTOME_G1_S_TRANSITION | 102 | 36 | 1.99283407294723 | 8.88477689519569e-14 | 1.55705715088304e-11 | DBF4,PRIM1,SKP2,ORC1L,PSMA7,TK1,PSMB4,POLE2,PSMB3,ORC6L,FBXO5,DHFR,PSMC4,PSMC2,PCNA,E2F1,CDT1,CCNE2,CCNE1,MCM8,CDC45L,MCM7,CDC7,CDC2,CDC6,MCM2,MCM4,CDK2,MCM6,RRM2,CKS1B,POLA2,TYMS,ORC2L,CDC25A,PSMD14 |
KEGG_CELL_CYCLE | 128 | 40 | 1.8630661979769 | 1.16939061088622e-13 | 1.63948563646248e-11 | DBF4,PKMYT1,PTTG2,PTTG1,CDKN2D,RBL2,RBL1,SKP2,ESPL1,ORC1L,MAD2L1,CHEK1,ORC6L,TFDP2,CDC20,CDC27,PCNA,E2F1,CCNE2,CCNE1,CDC45L,MCM7,CDC7,CDC6,CDC2,CDK6,MCM2,MCM4,CDK2,MCM6,CCND3,MDM2,BUB1B,YWHAZ,ORC2L,BUB3,CDC25C,CDC25A,CCNB2,YWHAQ |
Table 4. Get Full Table Top Pathways enriched with marker genes of identified cancer subtype 3 . Nof_Genes : No. of genes in this pathway. Nof_MarkerGenes : No. of marker genes of cancer subtype 3 in this pathway. Enrichment , p_value and q_value : See Methods & Data below. Marker_Gene: markers of cancer subtype 3 in this pathway
Pathway | Nof_Genes | Nof_MarkerGenes | Enrichment | p_value | q_value | Marker_Genes |
KEGG_ECM_RECEPTOR_INTERACTION | 84 | 34 | 2.16431824499125 | 6.94264145223942e-15 | 4.86679165801983e-12 | CHAD,CD44,SV2A,COL11A1,SDC1,COL1A2,LAMC2,COL1A1,TNC,COL3A1,ITGA11,ITGB3,HMMR,ITGAV,COL6A3,COL6A2,COL6A1,GP1BA,THBS1,LAMB1,THBS2,FN1,SPP1,COL4A4,ITGA1,ITGA2,ITGA3,COL5A3,COL5A2,COL5A1,LAMA4,LAMA3,ITGA5,ITGA7 |
KEGG_FOCAL_ADHESION | 201 | 51 | 1.50497354794751 | 3.00423776203428e-12 | 1.05298533559302e-09 | ACTG1,MYLK2,VEGFC,VEGFA,LAMC2,ITGA11,RAC2,LAMB1,SPP1,LAMA4,LAMA3,COL11A1,FLNC,CCND3,PARVB,COL3A1,COL6A3,COL6A2,COL6A1,THBS1,THBS2,CHAD,VCL,ACTN1,COL1A2,COL1A1,CAV2,ITGB3,MYL9,ITGAV,FN1,ITGA1,ITGA2,ITGA3,VAV1,ITGA5,ITGA7,MYLK,ZYX,AKT3,TNC,PPP1R12A,PIK3R3,FIGF,ACTB,COL4A4,FLT1,COL5A3,COL5A2,COL5A1,GRLF1 |
REACTOME_HEMOSTASIS | 273 | 51 | 1.05413532724082 | 2.81744368279108e-07 | 6.58342673878849e-05 | A2M,ATP1B3,SERPINE1,GNG7,F12,PLAUR,VEGFC,PPBP,VEGFA,TUBA4A,CALU,FCER1G,CD58,PLAU,PRSS8,LYN,GNB4,GNG12,THBS1,THBS2,SLC16A3,GNG10,SLC7A8,TGFB3,SLC7A7,VCL,SLC16A1,ACTN1,COL1A2,COL1A1,PPIL2,CLU,ITGB3,ITGAM,TIMP1,ITGAV,ADRA2C,SRGN,FN1,ITGA2,ITGA3,VAV1,ITGA5,TBXA2R,AKT3,TREM1,LCP2,LEFTY2,GP1BA,FIGF,SPARC |
REACTOME_POST_CHAPERONIN_TUBULIN_FOLDING_PATHWAY | 19 | 10 | 2.62117591996472 | 7.04541767961391e-07 | 0.000123470944835234 | TBCA,TBCD,TUBA3C,TUBA3D,TUBB6,TUBA4A,TUBA1A,TUBA1B,TUBA1C,TUBB3 |
REACTOME_AXON_GUIDANCE | 160 | 33 | 1.20068399059377 | 3.6413523045916e-06 | 0.000370362639147482 | PLXNA2,SEMA7A,ROBO2,PLXNB1,PLXNB3,COL1A2,COL1A1,MYL6,CACNB4,MYL9,RAC2,ITGA1,ABL2,NELL1,RHOC,PRSS8,RHOG,ARHGEF12,NCK1,PRNP,COL3A1,COL9A2,COL6A3,COL6A2,COL6A1,COL4A4,PTPRC,COL4A3,SERPINB8,DPYSL3,COL5A2,COL5A1,GRLF1 |
genes with copy number gain/loss: identified by the CopyNumber_Gistic2 pipeline
genes with mutation: identified by the Mutation_Significance pipeline
copy number gain/loss correlate with mRNA expression: identified by the Correlate_CopyNumber_vs_mRNA pipeline
marker genes of identified cancer subtypes: identified by the mRNAConsensusClustering pipeline
Let genes with copy number gain/loss or mutation be query genes. Let marker genes of specific identified subtypes be query genes. The Enrichment is calculated as:
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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 gain/loss or mutation, and the pathways that are enriched with markers genes of specific identified subtypes is measured by p-value.
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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.