GSEA (MOV10)

La hípotesis de GSEA es que cambios pequeños (que no serían detectados por los métodos ORA) pero coordinadosen conjuntos de genes funcionalmente relacionados también pueden tener efectos significativos. En este caso se consideran todos los genes estudiados. Este tipo de análisis puede ser útil en los casos que el análisis de expresión diferencial generé una lista pequeña de genes DE.

Vamos a realizar un análisis de sobrerepresentación con los genes diferencialmente expresados del dataset MOV10 (enlace).

Para realizar el análisis utilizaremos el paquete de Bioconductor clusterProfiler, tambien usaremos el paquete org.Hs.eg.db.

library(clusterProfiler)
library(org.Hs.eg.db)
library(enrichplot)
library(pathview)
library(ggplotify)
library(ggpubr)

Cargar datos

Cargamos los datos del análisis de expresion diferecial y creamos una lista de los genes ordenados por su FC.

df.fc <- read.csv('../rnaseq/deseq/data/resultado.csv')
df.fc <- df.fc[order(df.fc$log2FoldChange, decreasing = TRUE), ]

geneList <- df.fc$log2FoldChange
names(geneList) <- df.fc$X

head(geneList)
   HSPA6    MOV10    ASCL1    SCRT1  C1orf95   SNAP25 
6.221200 5.082196 4.348903 2.826439 1.902372 1.852436 

GO Gene Set Enrichment Analysis

Biological Process

go.BP <- gseGO(geneList    = geneList,
              OrgDb        = org.Hs.eg.db,
              keyType      = 'SYMBOL',
              ont          = "BP",
              minGSSize    = 100,
              maxGSSize    = 500,
              verbose      = FALSE)
head(go.BP)
ID Description setSize enrichmentScore NES pvalue p.adjust qvalue rank leading_edge core_enrichment
GO:0042254 GO:0042254 ribosome biogenesis 284 -0.4475101 -2.315861 0 0 0 4287 tags=49%, list=28%, signal=36% CINP/NSUN4/RPS23/NIP7/ERAL1/YBEY/RPS15/RPUSD2/RPL7L1/WDR46/GAR1/SBDS/RPS28/GEMIN4/BRIX1/EIF5/DCAF13/KAT2B/ABCE1/RPP25/SUV39H1/FBL/UTP18/HEATR3/RSL1D1/EIF2A/LTV1/NGDN/TSR1/RAN/NOP10/PA2G4/NOLC1/BYSL/MDN1/MRPS2/C1orf131/NOL8/MPV17L2/IMP3/WDR55/RRP1/FCF1/SURF6/UTP15/NUP88/RPL23A/FTSJ3/REXO4/PWP1/EXOSC3/DKC1/GTPBP10/FDXACB1/CUL4B/NOC4L/PWP2/EIF4A3/XRN2/URB1/SHQ1/RPP30/IMP4/MAK16/RPL26L1/EBNA1BP2/HEATR1/RRS1/RRP15/EXOSC10/DDX28/DDX21/DDX27/XRCC5/WDR43/RRP36/NSUN5/ISG20L2/EIF1AX/DDX47/ABT1/MRPL20/AATF/MPHOSPH10/TRMT112/NOL10/DDX54/NAT10/TSR2/NOC2L/EXOSC5/C1QBP/ERI3/DDX18/PELP1/TRMT2B/POP4/CUL4A/SDAD1/EXOSC6/UTP14A/EIF6/DHX30/NOL11/DDX49/WDR74/PES1/LSG1/NOP14/NOP16/DDX56/KRI1/DDX51/PDCD11/RPS19BP1/NOL9/NGRN/NOL6/MRTO4/GNL3L/SIRT7/NOP2/NHP2/EMG1/RPUSD4/RRP1B/RPSA/RRP7A/NLE1/RRP9/URB2/RPP40/GRWD1/MRPS7/PPAN/MYBBP1A/UTP20/DHX37/RPUSD1
GO:0022613 GO:0022613 ribonucleoprotein complex biogenesis 415 -0.4336013 -2.282947 0 0 0 4287 tags=48%, list=28%, signal=36% CINP/NSUN4/RPS23/NIP7/ERAL1/STRAP/YBEY/RPS15/RPUSD2/RPL7L1/WDR46/GAR1/SBDS/RPS28/GEMIN4/DDX42/BRIX1/SRPK1/EIF5/POLR2D/DCAF13/KAT2B/ABCE1/EIF3J/RPP25/SUV39H1/FBL/UTP18/SNRPD1/EIF3G/HEATR3/RSL1D1/EIF2A/LTV1/NGDN/TSR1/RAN/NOP10/PA2G4/GEMIN7/NOLC1/BYSL/MDN1/MRPS2/C1orf131/CELF1/NOL8/MPV17L2/IMP3/WDR55/RRP1/FCF1/LSM4/HSP90AB1/LSM2/SURF6/SNRPD2/RUVBL2/SNRPG/SF3B2/UTP15/NUP88/CLP1/RPL23A/USP4/FTSJ3/DENR/REXO4/PWP1/EXOSC3/EIF3I/DKC1/GTPBP10/FDXACB1/CUL4B/DICER1/NOC4L/PWP2/EIF4A3/XRN2/LUC7L2/URB1/CD2BP2/SF3A3/SHQ1/PRMT7/RPP30/IMP4/MAK16/HTATSF1/ADAR/RPL26L1/SF1/EBNA1BP2/HEATR1/RRS1/RRP15/EXOSC10/DDX28/SRSF6/DDX21/EIF3A/DDX27/XRCC5/PRPF6/WDR43/SF3B1/RRP36/DDX1/EIF3B/NSUN5/ISG20L2/EIF1AX/PRPF19/SFSWAP/DDX47/ABT1/COIL/SNRNP200/MRPL20/DDX23/NCBP1/AATF/MPHOSPH10/SNRPB/TRMT112/NOL10/DDX54/NAT10/TSR2/NOC2L/EXOSC5/C1QBP/ERI3/U2AF2/TSSC4/DDX18/PELP1/RUVBL1/TRMT2B/POP4/CUL4A/SDAD1/EXOSC6/UTP14A/EIF6/DHX30/NOL11/SNRPD3/DDX49/WDR74/PES1/LSG1/NOP14/NOP16/PUF60/PRMT5/DDX56/KRI1/SRSF9/DDX51/PDCD11/TARBP2/SNRPC/RPS19BP1/SF3B3/NOL9/PTBP2/NGRN/NOL6/MRTO4/PRPF8/GNL3L/SIRT7/PRPF3/NOP2/NHP2/EMG1/CPSF7/RPUSD4/RRP1B/DHX9/WDR77/RPSA/SF3B4/RRP7A/NLE1/RRP9/CELF2/SF3A1/URB2/RPP40/GRWD1/MRPS7/PPAN/MYBBP1A/UTP20/DHX37/RPUSD1
GO:0030198 GO:0030198 extracellular matrix organization 230 0.5478588 2.276120 0 0 0 3599 tags=47%, list=23%, signal=36% COL23A1/OLFML2A/ADAMTS7/COL5A1/ADAMTS2/ADAMTS1/COL13A1/DPP4/RECK/CREB3L1/ADAMTS10/LAMC1/ADAMTSL3/EGFLAM/COL2A1/SULF1/THSD4/MMP2/ITGA8/LAMA1/PAPLN/NTN4/NID2/LAMB1/MATN3/HAPLN2/COL3A1/NPNT/LUM/KAZALD1/RAMP2/CSGALNACT1/ABI3BP/SLC2A10/LOXL2/SOX9/LRP1/PDGFRA/ADAMTSL4/COL14A1/PTX3/COL4A4/ADAMTS18/COL27A1/LOXL4/ADAMTS4/OLFML2B/PXDN/COL24A1/MATN2/COL19A1/FBLN1/SMOC2/TGFB1/CAV2/APBB2/LAMB2/COL4A6/COL12A1/CAV1/NDNF/BCL3/ADAMTS3/TNF/ITGB1/GAS6/ADAMTS9/MMP14/WDR72/ADAMTS15/FKBP10/COL4A1/ADAMTS8/SERPINH1/APP/CCDC80/ERCC2/NPHP3/BMP1/FURIN/ADAMTS6/ADAMTS13/FLRT2/MMP15/MMP11/MMP16/FBLN5/PBXIP1/ZNF469/COL4A5/TGFBR3/GPM6B/HMCN1/COL18A1/NID1/HAS3/VPS33B/HAS2/P4HA1/COL4A3/PPARG/COMP/NOTCH1/COL15A1/KLK4/EXOC8/ITGB3
GO:0016072 GO:0016072 rRNA metabolic process 235 -0.4484916 -2.267449 0 0 0 4222 tags=47%, list=27%, signal=35% YBEY/RPS15/RPUSD2/RPL7L1/WDR46/GAR1/SBDS/RPS28/GEMIN4/BRIX1/DCAF13/KAT2B/RPP25/SUV39H1/FBL/UTP18/RSL1D1/NGDN/TSR1/NOP10/PA2G4/NOLC1/BYSL/GTF3C1/NOL8/IMP3/WDR55/RRP1/FCF1/UTP15/POLR1B/FTSJ3/REXO4/PWP1/EXOSC3/GTF3C5/DKC1/FDXACB1/MTOR/NOC4L/PWP2/EIF4A3/XRN2/POLR1E/URB1/SHQ1/RPP30/IMP4/MAK16/EBNA1BP2/HEATR1/RRS1/RRP15/EXOSC10/DDX21/DDX27/WDR43/RRP36/NCL/NSUN5/DDX47/ABT1/SPIN1/MPHOSPH10/TRMT112/NOL10/DDX54/NAT10/TSR2/EXOSC5/ERI3/DDX18/PELP1/TRMT2B/POP4/EXOSC6/UTP14A/SMARCA4/EIF6/NOL11/DDX49/WDR74/PES1/NOP14/GTF3C2/DDX56/KRI1/DDX51/PDCD11/NOL9/NOL6/MRTO4/SIRT7/NOP2/NHP2/EMG1/TCOF1/RPUSD4/RRP1B/BRF1/GTF3C6/RRP7A/DIS3L/POLR2E/RRP9/SMARCB1/RPP40/PPAN/UTP20/DHX37/RPUSD1
GO:0045229 GO:0045229 external encapsulating structure organization 231 0.5459670 2.266954 0 0 0 3599 tags=46%, list=23%, signal=36% COL23A1/OLFML2A/ADAMTS7/COL5A1/ADAMTS2/ADAMTS1/COL13A1/DPP4/RECK/CREB3L1/ADAMTS10/LAMC1/ADAMTSL3/EGFLAM/COL2A1/SULF1/THSD4/MMP2/ITGA8/LAMA1/PAPLN/NTN4/NID2/LAMB1/MATN3/HAPLN2/COL3A1/NPNT/LUM/KAZALD1/RAMP2/CSGALNACT1/ABI3BP/SLC2A10/LOXL2/SOX9/LRP1/PDGFRA/ADAMTSL4/COL14A1/PTX3/COL4A4/ADAMTS18/COL27A1/LOXL4/ADAMTS4/OLFML2B/PXDN/COL24A1/MATN2/COL19A1/FBLN1/SMOC2/TGFB1/CAV2/APBB2/LAMB2/COL4A6/COL12A1/CAV1/NDNF/BCL3/ADAMTS3/TNF/ITGB1/GAS6/ADAMTS9/MMP14/WDR72/ADAMTS15/FKBP10/COL4A1/ADAMTS8/SERPINH1/APP/CCDC80/ERCC2/NPHP3/BMP1/FURIN/ADAMTS6/ADAMTS13/FLRT2/MMP15/MMP11/MMP16/FBLN5/PBXIP1/ZNF469/COL4A5/TGFBR3/GPM6B/HMCN1/COL18A1/NID1/HAS3/VPS33B/HAS2/P4HA1/COL4A3/PPARG/COMP/NOTCH1/COL15A1/KLK4/EXOC8/ITGB3
GO:0043062 GO:0043062 extracellular structure organization 231 0.5457924 2.266229 0 0 0 3599 tags=46%, list=23%, signal=36% COL23A1/OLFML2A/ADAMTS7/COL5A1/ADAMTS2/ADAMTS1/COL13A1/DPP4/RECK/CREB3L1/ADAMTS10/LAMC1/ADAMTSL3/EGFLAM/COL2A1/SULF1/THSD4/MMP2/ITGA8/LAMA1/PAPLN/NTN4/NID2/LAMB1/MATN3/HAPLN2/COL3A1/NPNT/LUM/KAZALD1/RAMP2/CSGALNACT1/ABI3BP/SLC2A10/LOXL2/SOX9/LRP1/PDGFRA/ADAMTSL4/COL14A1/PTX3/COL4A4/ADAMTS18/COL27A1/LOXL4/ADAMTS4/OLFML2B/PXDN/COL24A1/MATN2/COL19A1/FBLN1/SMOC2/TGFB1/CAV2/APBB2/LAMB2/COL4A6/COL12A1/CAV1/NDNF/BCL3/ADAMTS3/TNF/ITGB1/GAS6/ADAMTS9/MMP14/WDR72/ADAMTS15/FKBP10/COL4A1/ADAMTS8/SERPINH1/APP/CCDC80/ERCC2/NPHP3/BMP1/FURIN/ADAMTS6/ADAMTS13/FLRT2/MMP15/MMP11/MMP16/FBLN5/PBXIP1/ZNF469/COL4A5/TGFBR3/GPM6B/HMCN1/COL18A1/NID1/HAS3/VPS33B/HAS2/P4HA1/COL4A3/PPARG/COMP/NOTCH1/COL15A1/KLK4/EXOC8/ITGB3
dotplot(go.BP, showCategory = 15)

f1 <- as.grob(gseaplot2(go.BP, geneSetID = 1, title = go.BP$Description[1]))
f2 <- as.grob(gseaplot2(go.BP, geneSetID = 2, title = go.BP$Description[2]))
f3 <- as.grob(gseaplot2(go.BP, geneSetID = 3, title = go.BP$Description[3]))
f4 <- as.grob(gseaplot2(go.BP, geneSetID = 4, title = go.BP$Description[4]))

ggarrange(f1, f2, f3, f4,
          ncol = 2, nrow = 2
        )

Molecular Functions

go.MF <- gseGO(geneList    = geneList,
              OrgDb        = org.Hs.eg.db,
              keyType      = 'SYMBOL',
              ont          = "MF",
              minGSSize    = 100,
              maxGSSize    = 500,
              verbose      = FALSE)
head(go.MF)
ID Description setSize enrichmentScore NES pvalue p.adjust qvalue rank leading_edge core_enrichment
GO:0005201 GO:0005201 extracellular matrix structural constituent 105 0.6417275 2.405642 0 0e+00 0e+00 1661 tags=44%, list=11%, signal=39% COL23A1/IGFBP7/COL5A1/COL6A2/HSPG2/COL13A1/FBN3/LAMC1/SRPX/ACAN/COL2A1/AGRN/THSD4/LAMA1/NID2/LAMB1/COL21A1/EFEMP1/MATN3/LTBP4/COL3A1/NPNT/LUM/THBS3/ABI3BP/FBN2/COL14A1/LAMA5/COL4A4/EDIL3/COL27A1/CRELD1/LTBP2/EMILIN3/ZP3/PXDN/COL24A1/SPON1/MATN2/COL19A1/FBLN1/LAMB2/COL4A6/LAMA4/COL12A1/VCAN
GO:0005509 GO:0005509 calcium ion binding 445 0.4432786 1.924595 0 0e+00 0e+00 3180 tags=35%, list=21%, signal=28% SLIT3/DCHS1/CDH23/SCUBE1/HSPG2/CAPN12/SCUBE3/FBN3/RASGRP2/SYT2/EGFLAM/SPOCK1/SYT17/AGRN/SULF1/ITGA5/NOTCH3/DLL1/NID2/GALNT3/EFEMP1/PCDH18/MATN3/LTBP4/MEGF6/SYT6/PCDHB10/DYSF/SNED1/NPNT/CDH3/ITPR3/CDHR1/THBS3/FAM20C/LRP2/NECAB2/EGFL7/HEG1/PLCB2/PCDHB11/LOXL2/TBC1D8B/FBN2/ENPP2/LRP1/KCNIP3/NINL/PAMR1/JAG1/PITPNM1/SCIN/DCHS2/CDH1/EDIL3/FAT4/LRP4/KCNIP2/CRELD1/LTBP2/VLDLR/SYT4/TTYH1/PADI2/PLA2G4A/ANXA1/EFHD1/MATN2/NUCB2/SLC25A25/PROS1/RAPGEF2/FBLN1/PCDH1/SMOC2/FSTL4/PRRG1/CHP2/P4HTM/PCDH10/HSPA5/PCDHB13/ITPR1/PCDHAC2/CDH4/RCN1/CRTAC1/EEF2K/CALML4/VCAN/CLGN/PCDH19/THBD/ANXA4/ENPP3/PLCD1/ITGB1/CDH20/FKBP14/GAS6/CETN3/TRPM4/BAIAP3/PCDH9/PCDH20/UNC13A/MEX3B/GCH1/PAM/RASGRP1/CELSR2/FKBP10/FSTL1/CELSR1/SYT12/ACTN2/S100P/GJB2/FER1L4/EGF/PCDHB14/BMP1/S100A11/ADAMTS13/TBC1D9/PCDHGA11/FAT3/THBS4/LDLR/PCLO/MAN1A1/DSC2/LTBP1/HRC/PPP2R3A/DGKA/FKBP9/FBLN5/CPNE1/EDEM3/PCDHB16/FAT1/NKD2/DNAH7/PCDHB2/HSP90B1/HMCN1/NCALD/NID1/MYL12A/GLCE/LTBP3/IQGAP1/CAPN2/RET
GO:0030545 GO:0030545 signaling receptor regulator activity 243 0.5066785 2.102458 0 0e+00 0e+00 2555 tags=37%, list=17%, signal=31% CRLF1/INHBE/SCG2/GDNF/MDK/IL11/EGFR/SEMA5B/DPP4/NRTN/GDF15/HSPA1A/TSLP/CXCL12/PGF/DLL1/CHGB/EFEMP1/ADM2/METRNL/IL32/HBEGF/FGF2/CD70/FGF23/FBN2/IL12A/INHBB/CCL20/PDE4D/JAG1/MANF/FLRT3/CSF1/IL18BP/STC1/SEMA4C/TNFSF9/ZP3/PXDN/GDF7/INHBA/SEMA4G/DKK3/FGF5/OSGIN1/FST/TGFB1/TNFSF10/FGF21/CXCL6/CMTM3/CTF1/WNT6/SEMA3E/BMP4/CLEC11A/SEMA6D/TNF/PDGFA/NPPC/GAS6/CSPG5/BMP3/GDF9/VEGFC/PDGFC/WNT11/EDA/LIF/CMTM8/NGF/IL23A/SEMA6B/WNT5B/NPFF/EGF/APP/MRAP2/BMP1/SEMA3D/DKK1/GPNMB/FGF19/HGF/FLRT2/NRG2/FLT3LG/SEMA3F/THBS4
GO:0030546 GO:0030546 signaling receptor activator activity 224 0.5079329 2.092207 0 1e-07 0e+00 2555 tags=38%, list=17%, signal=32% CRLF1/INHBE/SCG2/GDNF/MDK/IL11/EGFR/SEMA5B/DPP4/NRTN/GDF15/HSPA1A/TSLP/CXCL12/PGF/DLL1/CHGB/EFEMP1/ADM2/METRNL/IL32/HBEGF/FGF2/CD70/FGF23/FBN2/IL12A/INHBB/CCL20/JAG1/MANF/FLRT3/CSF1/STC1/SEMA4C/TNFSF9/ZP3/GDF7/INHBA/SEMA4G/FGF5/OSGIN1/TGFB1/TNFSF10/FGF21/CXCL6/CMTM3/CTF1/WNT6/SEMA3E/BMP4/CLEC11A/SEMA6D/TNF/PDGFA/NPPC/GAS6/CSPG5/BMP3/GDF9/VEGFC/PDGFC/WNT11/EDA/LIF/CMTM8/NGF/IL23A/SEMA6B/WNT5B/NPFF/EGF/APP/BMP1/SEMA3D/DKK1/GPNMB/FGF19/HGF/FLRT2/NRG2/FLT3LG/SEMA3F/THBS4
GO:0140640 GO:0140640 catalytic activity, acting on a nucleic acid 494 -0.3168737 -1.738354 0 1e-07 0e+00 3658 tags=36%, list=24%, signal=28% LIG1/BRIP1/SMUG1/MLH3/TERC/TSNAX/CHTF8/INO80/POLR2H/RPP14/DHX40/PARN/METTL2B/RAD51/RECQL5/POLA1/ERCC6L/DCP2/RAD51C/DDX12P/RAD54L2/ALKBH1/DALRD3/MCM4/RNASEK/POLR1C/POLR2A/RUVBL2/PGBD5/MSH3/POLR1B/SMARCAD1/MUTYH/QTRT1/FTSJ3/LARS2/POLR3K/EXOSC3/AARS2/THG1L/DKC1/DDX39A/FDXACB1/SUPV3L1/FTO/MCM3/DHX38/METTL6/HELLS/MCM2/DICER1/PCIF1/SAMHD1/EIF4A3/XRCC3/XRN2/PMS2/RBBP8/POLE/FARSB/ALKBH8/RNASEH2A/DFFB/MUS81/FARSA/DHX15/RPP30/TOP1/FEN1/DTWD2/SRCAP/POLR3F/CHRAC1/DBR1/IGHMBP2/MCM7/DNA2/EXOSC10/DDX28/DDX21/DDX27/XRCC5/CHD4/SMARCAL1/ELAC1/DDX1/MLH1/POLR2B/CRCP/NSUN5/POLR2J2/ISG20L2/QRSL1/DDX47/MED20/POLR3B/SNRNP200/DDX23/MSH2/DHX33/ERCC3/TRPT1/DDX54/TOE1/EXOSC5/CNOT7/ERI3/PPP1R8/APEX2/POLR2I/DDX18/POLRMT/RUVBL1/WRNIP1/RAD51D/TRMT2B/POP4/WARS2/DDX19A/RTEL1/PTRHD1/SMARCA4/NTHL1/DHX30/YTHDC2/DDX49/OGG1/POLR3A/ALKBH4/DDX56/DHX16/LCMT2/NSUN2/DDX51/TYW3/POLN/EARS2/POLR1A/GEN1/MAU2/RAD50/XRCC6/ALKBH5/MEPCE/LRRC47/POLR2J/PIF1/POLM/TRMU/DUS3L/TDG/NOP2/EMG1/POP1/DUS1L/DHX9/PUS1/DDX6/DIS3L/POLR2E/POLR2L/TRMT1/CARS2/SMG6/NME1/ANGEL2/RPP40/POLR2F/APEX1/METTL1/DHX34/POLE4/DHX37/TRMT61A/POLR3H/EME2/MSH4
GO:0048018 GO:0048018 receptor ligand activity 219 0.5104062 2.102871 0 1e-07 1e-07 2555 tags=38%, list=17%, signal=32% CRLF1/INHBE/SCG2/GDNF/MDK/IL11/SEMA5B/DPP4/NRTN/GDF15/HSPA1A/TSLP/CXCL12/PGF/DLL1/CHGB/EFEMP1/ADM2/METRNL/IL32/HBEGF/FGF2/CD70/FGF23/FBN2/IL12A/INHBB/CCL20/JAG1/MANF/FLRT3/CSF1/STC1/SEMA4C/TNFSF9/ZP3/GDF7/INHBA/SEMA4G/FGF5/OSGIN1/TGFB1/TNFSF10/FGF21/CXCL6/CMTM3/CTF1/WNT6/SEMA3E/BMP4/CLEC11A/SEMA6D/TNF/PDGFA/NPPC/GAS6/CSPG5/BMP3/GDF9/VEGFC/PDGFC/WNT11/EDA/LIF/CMTM8/NGF/IL23A/SEMA6B/WNT5B/NPFF/EGF/APP/BMP1/SEMA3D/DKK1/GPNMB/FGF19/HGF/FLRT2/NRG2/FLT3LG/SEMA3F/THBS4
dotplot(go.MF, showCategory = 15)

f1 <- as.grob(gseaplot2(go.MF, geneSetID = 1, title = go.MF$Description[1]))
f2 <- as.grob(gseaplot2(go.MF, geneSetID = 2, title = go.MF$Description[2]))
f3 <- as.grob(gseaplot2(go.MF, geneSetID = 3, title = go.MF$Description[3]))
f4 <- as.grob(gseaplot2(go.MF, geneSetID = 4, title = go.MF$Description[4]))

ggarrange(f1, f2, f3, f4,
          ncol = 2, nrow = 2
        )

Cellular Components

go.CC <- gseGO(geneList    = geneList,
              OrgDb        = org.Hs.eg.db,
              keyType      = 'SYMBOL',
              ont          = "CC",
              minGSSize    = 100,
              maxGSSize    = 500,
              verbose      = FALSE)
head(go.CC)
ID Description setSize enrichmentScore NES pvalue p.adjust qvalue rank leading_edge core_enrichment
GO:0062023 GO:0062023 collagen-containing extracellular matrix 259 0.5900663 2.478964 0 0 0 3260 tags=51%, list=21%, signal=41% ACHE/INHBE/COL23A1/IGFBP7/MDK/HTRA1/COL5A1/ADAMTS2/COL6A2/ADAMTS1/HSPG2/COL13A1/ITIH5/GDF15/ADAMTS10/LAMC1/SRPX/ACAN/EGFLAM/COL2A1/CXCL12/AGRN/SULF1/THSD4/MMP2/BCAM/LAMA1/NTN4/NID2/LAMB1/COL21A1/EFEMP1/MATN3/LTBP4/HAPLN2/COL3A1/NPNT/LUM/THBS3/KAZALD1/ABI3BP/EGFL7/LOXL2/FBN2/CLU/TIMP3/ADAMTSL4/COL14A1/LAMA5/SERPING1/ACTA2/COL4A4/EDIL3/COL27A1/LOXL4/FREM2/CSPG4/ADAMTS4/CRELD1/LTBP2/EMILIN3/ZP3/PXDN/COCH/GPC6/COL24A1/SPON1/ITGB4/ANXA1/ADAM11/MATN2/L1CAM/COL19A1/FBLN1/SMOC2/CTSC/LAMC3/TGFB1/ADAM19/NAV2/LAMB2/COL4A6/LAMA4/COL12A1/VCAN/SERPINE2/ANXA4/ANXA5/ADAMTS3/GPC5/ADAMTS9/SERPINF1/GPC4/ADAMTS15/FN1/LAMA3/LMAN1/GPC3/COL4A1/WNT5B/HAPLN3/TNC/ADAMTS8/SERPINH1/CCDC80/LGALS3BP/THBS4/LTBP1/APOE/NCAM1/FBLN5/COL4A5/EMILIN2/SFRP1/DCN/HSP90B1/FREM1/MFAP2/C17orf58/HMCN1/COL18A1/SDC3/ANGPTL2/COLEC12/NID1/ANG/LTBP3/MFGE8/COL25A1/FRAS1/GPC1
GO:0030312 GO:0030312 external encapsulating structure 335 0.5716858 2.446870 0 0 0 3260 tags=49%, list=21%, signal=39% ACHE/INHBE/COL23A1/OLFML2A/IGFBP7/MDK/ADAMTS7/HTRA1/COL5A1/ADAMTS2/COL6A2/ADAMTS1/HSPG2/COL13A1/ITIH5/GDF15/FBN3/ADAMTS10/LAMC1/SRPX/ACAN/ADAMTSL3/EGFLAM/COL2A1/CXCL12/AGRN/SULF1/THSD4/MMP2/BCAM/LAMA1/NTN4/NID2/LAMB1/COL21A1/EFEMP1/MATN3/LTBP4/HAPLN2/SNED1/COL3A1/NPNT/LUM/THBS3/ELFN1/KAZALD1/ELFN2/ABI3BP/EGFL7/LOXL2/FBN2/CLU/TIMP3/ADAMTSL4/COL14A1/LAMA5/EMID1/SERPING1/ACTA2/PTX3/LRIG3/FLRT3/COL4A4/ADAMTS18/EDIL3/COL27A1/LOXL4/FREM2/CSPG4/ADAMTS4/CRELD1/OLFML2B/LTBP2/EMILIN3/ZP3/PXDN/COCH/GPC6/COL24A1/SPON1/ITGB4/ANXA1/ADAM11/MATN2/OVGP1/L1CAM/COL19A1/FBLN1/LRRN2/SMOC2/CTSC/LAMC3/TGFB1/ADAM19/NAV2/LAMB2/RTN4RL2/COL4A6/LAMA4/LINGO1/COL12A1/WNT6/VCAN/SERPINE2/NDNF/GLG1/ANXA4/ANXA5/ADAMTS3/GPC5/WNT11/ADAMTS9/MMP14/SERPINF1/GPC4/ADAMTS15/LRIG1/FN1/LAMA3/LMAN1/GPC3/COL4A1/WNT5B/HAPLN3/TNC/ADAMTS8/SERPINH1/CCDC80/ADAMTS6/ADAMTS13/FLRT2/LGALS3BP/LINGO3/THBS4/TLR3/MMP15/LTBP1/APOE/NCAM1/MMP11/MMP16/FBLN5/COL4A5/EMILIN2/SFRP1/DCN/HSP90B1/FREM1/MFAP2/C17orf58/HMCN1/COL18A1/FLRT1/SDC3/ANGPTL2/COLEC12/NID1/ANG/LTBP3/MFGE8/COL25A1/TRIL/FRAS1/GPC1
GO:0031012 GO:0031012 extracellular matrix 335 0.5716858 2.446870 0 0 0 3260 tags=49%, list=21%, signal=39% ACHE/INHBE/COL23A1/OLFML2A/IGFBP7/MDK/ADAMTS7/HTRA1/COL5A1/ADAMTS2/COL6A2/ADAMTS1/HSPG2/COL13A1/ITIH5/GDF15/FBN3/ADAMTS10/LAMC1/SRPX/ACAN/ADAMTSL3/EGFLAM/COL2A1/CXCL12/AGRN/SULF1/THSD4/MMP2/BCAM/LAMA1/NTN4/NID2/LAMB1/COL21A1/EFEMP1/MATN3/LTBP4/HAPLN2/SNED1/COL3A1/NPNT/LUM/THBS3/ELFN1/KAZALD1/ELFN2/ABI3BP/EGFL7/LOXL2/FBN2/CLU/TIMP3/ADAMTSL4/COL14A1/LAMA5/EMID1/SERPING1/ACTA2/PTX3/LRIG3/FLRT3/COL4A4/ADAMTS18/EDIL3/COL27A1/LOXL4/FREM2/CSPG4/ADAMTS4/CRELD1/OLFML2B/LTBP2/EMILIN3/ZP3/PXDN/COCH/GPC6/COL24A1/SPON1/ITGB4/ANXA1/ADAM11/MATN2/OVGP1/L1CAM/COL19A1/FBLN1/LRRN2/SMOC2/CTSC/LAMC3/TGFB1/ADAM19/NAV2/LAMB2/RTN4RL2/COL4A6/LAMA4/LINGO1/COL12A1/WNT6/VCAN/SERPINE2/NDNF/GLG1/ANXA4/ANXA5/ADAMTS3/GPC5/WNT11/ADAMTS9/MMP14/SERPINF1/GPC4/ADAMTS15/LRIG1/FN1/LAMA3/LMAN1/GPC3/COL4A1/WNT5B/HAPLN3/TNC/ADAMTS8/SERPINH1/CCDC80/ADAMTS6/ADAMTS13/FLRT2/LGALS3BP/LINGO3/THBS4/TLR3/MMP15/LTBP1/APOE/NCAM1/MMP11/MMP16/FBLN5/COL4A5/EMILIN2/SFRP1/DCN/HSP90B1/FREM1/MFAP2/C17orf58/HMCN1/COL18A1/FLRT1/SDC3/ANGPTL2/COLEC12/NID1/ANG/LTBP3/MFGE8/COL25A1/TRIL/FRAS1/GPC1
GO:0098687 GO:0098687 chromosomal region 332 -0.4116229 -2.156838 0 0 0 4127 tags=45%, list=27%, signal=33% GAR1/PPP1R10/HJURP/NDE1/RPA2/SMARCA5/CHMP7/SIN3A/TP53BP1/NUP107/ORC3/KAT2B/SPAG5/SEC13/SUV39H1/GATAD2B/ORC1/MEAF6/AURKB/TERC/NGDN/DCTN3/ZNF618/CHMP3/RAD51/ERCC6L/TEX14/NSL1/DYNC1LI1/DCTN1/TRAPPC12/BOD1/SMARCE1/CDCA8/ZWILCH/MCM4/FBXW11/CENPT/THOC6/PHF2/FBXO28/THOC1/PLK1/ANAPC16/WDR82/EID3/DAXX/PPP2CA/BRD7/PDS5A/MCM3/HELLS/MCM2/HSF1/XRCC3/SUMO3/THOC7/SMC3/CBX1/MTBP/SIRT2/RCC2/ARID2/SPDYA/CDC20/FEN1/ACD/CENPV/CHRAC1/FMR1/NUP98/KIF2C/MCM7/DNA2/SEH1L/HNRNPU/KIF22/XRCC5/SMARCD1/NUP85/CHD4/SMC1A/ZWINT/BAZ1B/POLR2B/SNAI1/NBN/SPC24/FLYWCH1/LRWD1/EZH1/ACTL6A/SPC25/RANGAP1/MSH2/DCTN4/CENPN/CHMP4A/SKA1/NAT10/KDM4A/INCENP/MTA2/WRNIP1/CENPB/RAD51D/PMF1/RTEL1/RPA1/SMARCA4/CENPM/CHMP4B/MEN1/ZW10/SIRT6/C9orf78/DCTN5/PBRM1/TELO2/TFIP11/BIRC5/PARP1/CCNB1/PPP2R1A/PSEN2/RPA4/RAD50/PHF6/STAG1/XRCC6/SKA3/PIF1/DDB1/PPP1CA/CENPI/KAT5/ALYREF/NHP2/CTCF/SMARCC1/CDCA5/CHAMP1/CHMP1A/SMG6/SMARCB1/CHMP6/ACTB/APEX1
GO:0098798 GO:0098798 mitochondrial protein-containing complex 238 -0.4230790 -2.114767 0 0 0 5011 tags=53%, list=33%, signal=37% TIMM8B/UQCRQ/MRPL55/UQCRH/NDUFV1/MRPL2/PHB2/MRPL18/FOXRED1/MRPL43/MRPS22/PAM16/MRPS24/MRPL16/MRPS31/MRPL24/TIMM44/COX5A/CYC1/MRPL30/PDHX/MRPL3/NDUFC1/NSUN4/PMPCA/TIMM17B/MRPL9/NDUFA1/TOMM5/MRPS15/MRPL48/NDUFB9/COX5B/IDH3G/GRPEL1/MRPL51/TIMM22/NDUFV2/NDUFB7/NFS1/MRPS26/MRPS18A/NDUFB10/NDUFA3/MRPL47/MRPS2/SDHC/COX7C/NDUFAB1/MPV17L2/PDHA2/NDUFA11/MRPL40/ISCU/AURKAIP1/MRPS18B/MRPS23/DLD/TOMM20/MRPL46/VDAC1/MRPL49/UQCR11/NDUFA12/MCCC2/MRPS10/SUPV3L1/NDUFB11/AGK/NDUFC2/MRPL52/MRPL44/MRPL14/TIMM13/NDUFS8/PDHA1/MRPL15/MRPL38/NDUFS5/MRPL37/MRPS16/TIMM23/NDUFB8/MRPL53/DNA2/MRPL28/SAMM50/DLAT/MTX1/COX6B1/LYRM4/MRPL45/MRPL1/MRPS12/MRPL41/MRPL12/MRPL20/NDUFA8/TIMM50/NDUFS3/NDUFS2/PPIF/POLRMT/MRPL35/MRPS11/BCS1L/MRPL11/MRPS35/TOMM22/FXN/MRPL23/MRPL4/PDK2/NDUFS6/TOMM40L/TOMM6/IDH3B/MRPL54/NDUFB2/GADD45GIP1/HSD17B10/BAX/DNAJC11/MRPL27/MRPS7/TOMM40/TIMM10
GO:0009897 GO:0009897 external side of plasma membrane 200 0.5379539 2.209822 0 0 0 3218 tags=47%, list=21%, signal=38% CRLF1/FCGRT/SCUBE1/PLAU/TNFRSF9/TNFRSF13C/ACE/ABCA1/CXCL12/CD24/ITGA5/BCAM/ATP1B2/ITGA8/ITGA11/ULBP2/IL1R1/MCAM/ITGA4/LRP2/OSMR/ITGA9/MR1/HEG1/S1PR1/MICB/ULBP1/FAS/HLA-B/PDGFRA/FCRLB/ADAM21/CNTFR/GFRA1/ADAM9/NT5E/ITGA6/BTNL9/LEPR/CCR10/BTN3A3/BTN2A2/BTN3A2/TGFBR2/HLA-F/ITGA3/BTN2A3P/CD1D/IL27RA/RTN4RL2/ENPEP/BTN3A1/KCNJ3/IL6R/EPHA5/CLEC4F/CHRNA4/IL4R/THBD/ENPP3/ANXA5/ITGA1/TNF/ITGB1/CX3CR1/SLC2A4/AQP4/SDC1/ITGAL/INSR/ITGA7/KIT/GPC4/GHR/ADA/EPOR/IGSF21/ABCG1/LDLR/HLA-E/NCAM1/HLA-C/IL2RG/ALCAM/TGFBR3/B2M/CXCR4/SLC38A1/LIFR/CD14/CAPN2/IL11RA/MFGE8/RAET1G
dotplot(go.CC, showCategory = 15)

f1 <- as.grob(gseaplot2(go.CC, geneSetID = 1, title = go.CC$Description[1]))
f2 <- as.grob(gseaplot2(go.CC, geneSetID = 2, title = go.CC$Description[2]))
f3 <- as.grob(gseaplot2(go.CC, geneSetID = 3, title = go.CC$Description[3]))
f4 <- as.grob(gseaplot2(go.CC, geneSetID = 4, title = go.CC$Description[4]))

ggarrange(f1, f2, f3, f4,
          ncol = 2, nrow = 2
        )

KEGG pathway gene set enrichment analysis

Primero debemos de obtener los valores de ENTREZID de los genes.

allgenes.entrezid <- bitr(names(geneList), 
                          fromType = 'SYMBOL',
                          toType = 'ENTREZID',
                          OrgDb = 'org.Hs.eg.db'
                          )
geneList.kegg <- geneList
names(geneList.kegg) <- allgenes.entrezid$ENTREZID

head(geneList.kegg)
    3310     4343      429    83482     6616       43 
6.221200 5.082196 4.348903 2.826439 1.902372 1.852436 
gsea.kegg <- gseKEGG(geneList     = geneList.kegg,
                     organism     = 'hsa',
                     minGSSize    = 120,
                     verbose      = FALSE)

head(gsea.kegg)
ID Description setSize enrichmentScore NES pvalue p.adjust qvalue rank leading_edge core_enrichment
hsa05168 hsa05168 Herpes simplex virus 1 infection 428 0.5772203 2.501456 0 0e+00 0e+00 3306 tags=46%, list=22%, signal=37% 7738/10172/148268/147686/155054/163059/51276/199704/152687/147837/79973/3678/684/7539/126295/342892/55659/10520/10781/199692/10794/284307/388558/9451/163081/7561/90594/148254/10308/148266/147687/10795/9534/7673/7637/147923/342909/355/3106/3592/729747/64135/57573/92283/9422/284370/390980/126231/80778/168374/100131827/374900/93474/7188/84765/7638/140612/84436/57711/5293/163227/84874/79744/57232/3134/162972/7733/201514/7752/162655/339500/92285/90075/55769/117608/7594/80095/79862/162962/374899/7189/58500/146198/7700/342908/7565/1147/9668/7768/84914/163131/55552/10224/374879/148103/7554/84911/54811/90589/7770/7124/84503/65251/284349/57677/83744/7633/219749/7711/388536/169841/162993/7766/163255/90592/84527/285268/9831/163049/340252/7556/7699/400713/10793/126070/147949/163087/284371/728927/7773/348327/7644/51710/125893/374928/163051/94039/8892/7695/284390/170959/3133/7098/147694/6892/7639/91120/284309/3459/3107/79724/29915/148203/58492/567/6432/54807/170960/22835/390927/146434/51427/7692/90321/388566/80110/7574/7767/3105/55713/126375/7576/127396/170958/80264/3690/84924/126068/9310/57547/90576/26974/641339/8717/8772/6428/9021/59348/91664/330/353355/349075/125919/91975/4792
hsa04060 hsa04060 Cytokine-cytokine receptor interaction 124 0.6400572 2.475342 0 0e+00 0e+00 2988 tags=51%, list=19%, signal=41% 83729/3589/9518/3604/115650/85480/6387/130399/3554/9235/9180/970/355/3592/3625/1271/6364/3953/51330/60401/2826/1435/27242/8744/7048/151449/3624/9466/7040/8743/8809/3570/3588/6372/8795/1489/3566/652/7124/1524/651/2661/3601/1896/3976/8793/2690/4803/51561/2057/55540/3459/3561/84818/768211/7852/2920/7066/3977/3590/3587/2660/2919
hsa04151 hsa04151 PI3K-Akt signaling pathway 276 0.5293662 2.214544 0 0e+00 0e+00 3349 tags=40%, list=22%, signal=32% 2668/5105/1956/1292/4902/90993/3915/1280/5228/1026/3678/8516/284217/22801/54541/3912/64764/1942/3718/2065/9863/595/7059/3676/9180/10161/3680/2247/8074/4609/4602/5156/3655/3911/9586/1943/2786/1435/1286/5293/5106/3691/3675/10319/2250/3913/2792/26291/3570/1288/1147/3910/3566/23533/5879/3672/5154/3688/2149/7424/56034/6198/3643/3679/3815/2690/3696/2335/4803/3909/1282/5894/29941/2057/1950/3371/9965/3082/2323/7060/23566/5563/4908/5523/3561/1287/3693/118788/7184/55970/1969/3667/23035/5979/6655/148327/1285/1311/3690/2321/2788/9170/284/1284/2064/55012/2784/894/1021/2322
hsa05200 hsa05200 Pathways in cancer 436 0.4227458 1.834197 0 1e-07 0e+00 3462 tags=32%, list=23%, signal=25% 1956/10235/3915/6387/5228/1026/4313/4854/284217/28514/3912/388585/624/3718/595/5366/1647/10161/840/2247/1643/8074/5330/4609/2735/5915/8322/355/5156/3592/113/3655/3911/1910/182/2786/3725/1286/7188/999/111/5293/7048/3675/816/10319/2250/7040/7189/5292/3913/2792/185/26291/3570/1288/1147/3910/1030/91860/3566/7475/1164/9252/652/5879/5154/3688/23604/2149/7424/5337/7481/3601/6198/3815/10125/2335/1163/3909/51561/1282/81029/5894/2057/6093/1950/4040/1909/3280/9965/3082/4843/3162/2323/1499/23566/3459/3561/1287/7184/55970/7709/6932/7852/5979/3091/6655/112/5338/7855/5732/54361/1285/5468/10023/4851/8326/2788/7043/9170/1284/115/8772/2064/11186/330/2784/4792/894/1021/2322/6667/7473/89780/7422/23493/6199/5336
hsa04820 hsa04820 Cytoskeleton in muscle cells 176 0.5244601 2.101264 0 1e-07 0e+00 3175 tags=38%, list=21%, signal=31% 1289/1292/3339/84467/25802/84033/375790/3678/482/8516/284217/22801/2027/22795/2318/1281/7059/3676/3680/2201/3655/287/1286/85301/255631/3691/7138/8572/3675/2192/271/8910/6385/1288/1462/3672/3688/6382/3679/23345/3696/2335/88/1282/23500/6640/7060/114793/1824/1466/27063/1287/3693/1634/9672/4811/1285/1730/1311/25777/7414/23224/6641/3690/4001/752/1284
hsa04080 hsa04080 Neuroactive ligand-receptor interaction 152 0.5312897 2.099922 0 2e-07 1e-07 4074 tags=53%, list=27%, signal=39% 1394/117/2696/22953/11255/624/79924/6752/10161/53637/1901/3352/3953/5028/1910/55584/152/10316/344838/79957/1132/185/116444/5029/706/1137/154/2901/2149/153/2690/2906/2899/8620/84109/1909/2743/23566/2894/135/1136/5745/51083/3269/2914/7434/5732/1815/136/10886/2796/2563/55879/4985/10203/2892/89832/9170/2900/2560/10424/797/552/2557/1902/6863/799/27346/7349/59340/5027/5443/3363/6019/7425/1903/6013/4922/887/1143
dotplot(gsea.kegg, showCategory = 15)

f1 <- as.grob(gseaplot2(gsea.kegg, geneSetID = 1, title = gsea.kegg$Description[1]))
f2 <- as.grob(gseaplot2(gsea.kegg, geneSetID = 2, title = gsea.kegg$Description[2]))
f3 <- as.grob(gseaplot2(gsea.kegg, geneSetID = 3, title = gsea.kegg$Description[3]))
f4 <- as.grob(gseaplot2(gsea.kegg, geneSetID = 4, title = gsea.kegg$Description[4]))

ggarrange(f1, f2, f3, f4,
          ncol = 2, nrow = 2
        )

Pathways

core <- geneInCategory(gsea.kegg)[['hsa05168']]

hsa05168 <- pathview(gene.data  = geneList.kegg,
                     pathway.id = "hsa05168",
                     species    = "hsa",
                     limit      = list(gene=round(max(abs(geneList.kegg[core])),1), cpd=1))

core <- geneInCategory(gsea.kegg)[['hsa04060']]

hsa04060 <- pathview(gene.data  = geneList.kegg,
                     pathway.id = "hsa04060",
                     species    = "hsa",
                     limit      = list(gene=round(max(abs(geneList.kegg[core])), 1), cpd=1))

Referencias

Harvard Chan Bioinformatics Core (HBC).

citation("clusterProfiler")
Please cite S. Xu (2024) for using clusterProfiler. In addition, please
cite G. Yu (2010) when using GOSemSim, G. Yu (2015) when using DOSE and
G. Yu (2015) when using ChIPseeker.

  S Xu, E Hu, Y Cai, Z Xie, X Luo, L Zhan, W Tang, Q Wang, B Liu, R
  Wang, W Xie, T Wu, L Xie, G Yu. Using clusterProfiler to characterize
  multiomics data. Nature Protocols. 2024,
  doi:10.1038/s41596-024-01020-z

  T Wu, E Hu, S Xu, M Chen, P Guo, Z Dai, T Feng, L Zhou, W Tang, L
  Zhan, X Fu, S Liu, X Bo, and G Yu. clusterProfiler 4.0: A universal
  enrichment tool for interpreting omics data. The Innovation. 2021,
  2(3):100141

  Guangchuang Yu, Li-Gen Wang, Yanyan Han and Qing-Yu He.
  clusterProfiler: an R package for comparing biological themes among
  gene clusters. OMICS: A Journal of Integrative Biology 2012,
  16(5):284-287

To see these entries in BibTeX format, use 'print(<citation>,
bibtex=TRUE)', 'toBibtex(.)', or set
'options(citation.bibtex.max=999)'.