9 Reactome enrichment analysis
ReactomePA is designed for reactome pathway based analysis (Yu and He 2016). Reactome is an open-source, open access, manually curated and peer-reviewed pathway database.
9.1 Supported organisms
Currently ReactomePA supports several model organisms, including ‘celegans’, ‘fly’, ‘human’, ‘mouse’, ‘rat’, ‘yeast’ and ‘zebrafish’. The input gene ID should be Entrez gene ID. We recommend using clusterProfiler::bitr() to convert biological IDs.
9.2 Reactome pathway over-representation analysis
Enrichment analysis is a widely used approach to identify biological
themes. ReactomePA implemented enrichPathway() that uses hypergeometric model to assess whether the number of selected genes associated with a reactome pathway is larger than expected.
library(ReactomePA)
data(geneList, package="DOSE"
)
de <- names(geneList)[abs(geneList) > 1.5]
head(de)## [1] "4312" "8318" "10874" "55143" "55388" "991"
x <- enrichPathway(gene=de, pvalueCutoff = 0.05, readable=TRUE)
head(x)## ID
## R-HSA-69620 R-HSA-69620
## R-HSA-69618 R-HSA-69618
## R-HSA-2500257 R-HSA-2500257
## R-HSA-141424 R-HSA-141424
## R-HSA-141444 R-HSA-141444
## R-HSA-9648025 R-HSA-9648025
## Description
## R-HSA-69620 Cell Cycle Checkpoints
## R-HSA-69618 Mitotic Spindle Checkpoint
## R-HSA-2500257 Resolution of Sister Chromatid Cohesion
## R-HSA-141424 Amplification of signal from the kinetochores
## R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
## R-HSA-9648025 EML4 and NUDC in mitotic spindle formation
## GeneRatio BgRatio pvalue p.adjust qvalue
## R-HSA-69620 38/330 294/10867 2.529789e-14 1.970705e-11 1.754874e-11
## R-HSA-69618 22/330 113/10867 2.443911e-12 8.189225e-10 7.292344e-10
## R-HSA-2500257 23/330 126/10867 3.153745e-12 8.189225e-10 7.292344e-10
## R-HSA-141424 20/330 96/10867 6.665836e-12 1.038537e-09 9.247970e-10
## R-HSA-141444 20/330 96/10867 6.665836e-12 1.038537e-09 9.247970e-10
## R-HSA-9648025 20/330 117/10867 2.927596e-10 3.800995e-08 3.384712e-08
## geneID
## R-HSA-69620 CDC45/CDCA8/MCM10/CDC20/CENPE/CCNB2/NDC80/UBE2C/SKA1/CENPM/CENPN/UBE2S/CCNA2/CDK1/ERCC6L/MAD2L1/KIF18A/BIRC5/AURKB/CHEK1/CCNB1/MCM5/MCM2/KIF2C/CDC25A/CDC6/PLK1/BUB1B/GTSE1/EXO1/ZWINT/CENPU/SPC25/CENPI/CCNE1/ORC6/ORC1/TAOK1
## R-HSA-69618 CDCA8/CDC20/CENPE/NDC80/UBE2C/SKA1/CENPM/CENPN/UBE2S/ERCC6L/MAD2L1/KIF18A/BIRC5/AURKB/KIF2C/PLK1/BUB1B/ZWINT/CENPU/SPC25/CENPI/TAOK1
## R-HSA-2500257 CDCA8/CDC20/CENPE/CCNB2/NDC80/SKA1/CENPM/CENPN/CDK1/ERCC6L/MAD2L1/KIF18A/BIRC5/AURKB/CCNB1/KIF2C/PLK1/BUB1B/ZWINT/CENPU/SPC25/CENPI/TAOK1
## R-HSA-141424 CDCA8/CDC20/CENPE/NDC80/SKA1/CENPM/CENPN/ERCC6L/MAD2L1/KIF18A/BIRC5/AURKB/KIF2C/PLK1/BUB1B/ZWINT/CENPU/SPC25/CENPI/TAOK1
## R-HSA-141444 CDCA8/CDC20/CENPE/NDC80/SKA1/CENPM/CENPN/ERCC6L/MAD2L1/KIF18A/BIRC5/AURKB/KIF2C/PLK1/BUB1B/ZWINT/CENPU/SPC25/CENPI/TAOK1
## R-HSA-9648025 CDCA8/CDC20/CENPE/NDC80/SKA1/CENPM/CENPN/ERCC6L/MAD2L1/KIF18A/BIRC5/AURKB/KIF2C/PLK1/BUB1B/ZWINT/CENPU/SPC25/CENPI/TAOK1
## Count
## R-HSA-69620 38
## R-HSA-69618 22
## R-HSA-2500257 23
## R-HSA-141424 20
## R-HSA-141444 20
## R-HSA-9648025 209.3 Reactome pathway gene set enrichment analysis
y <- gsePathway(geneList,
pvalueCutoff = 0.2,
pAdjustMethod = "BH",
verbose = FALSE)
head(y)## ID Description setSize
## R-HSA-69620 R-HSA-69620 Cell Cycle Checkpoints 238
## R-HSA-453279 R-HSA-453279 Mitotic G1 phase and G1/S transition 142
## R-HSA-69306 R-HSA-69306 DNA Replication 117
## R-HSA-69278 R-HSA-69278 Cell Cycle, Mitotic 457
## R-HSA-69206 R-HSA-69206 G1/S Transition 124
## R-HSA-2555396 R-HSA-2555396 Mitotic Metaphase and Anaphase 200
## enrichmentScore NES pvalue p.adjust qvalues rank
## R-HSA-69620 0.6675566 3.073841 1e-10 4.14e-09 3.055639e-09 1905
## R-HSA-453279 0.7016040 3.031248 1e-10 4.14e-09 3.055639e-09 1155
## R-HSA-69306 0.7233886 3.012019 1e-10 4.14e-09 3.055639e-09 1769
## R-HSA-69278 0.6077642 2.980196 1e-10 4.14e-09 3.055639e-09 1769
## R-HSA-69206 0.7046866 2.973447 1e-10 4.14e-09 3.055639e-09 1155
## R-HSA-2555396 0.6499708 2.937479 1e-10 4.14e-09 3.055639e-09 1857
## leading_edge
## R-HSA-69620 tags=43%, list=15%, signal=37%
## R-HSA-453279 tags=41%, list=9%, signal=37%
## R-HSA-69306 tags=53%, list=14%, signal=46%
## R-HSA-69278 tags=36%, list=14%, signal=32%
## R-HSA-69206 tags=42%, list=9%, signal=38%
## R-HSA-2555396 tags=40%, list=15%, signal=34%
## core_enrichment
## R-HSA-69620 8318/55143/55388/991/1062/9133/10403/11065/220134/79019/55839/27338/890/983/54821/4085/81930/332/9212/1111/891/4174/4171/11004/993/990/5347/701/51512/9156/11130/79682/57405/2491/898/23594/4998/9134/4175/4173/10926/5984/1058/699/1063/85236/5688/5709/55055/641/1029/5698/1763/8970/5693/8317/4176/5713/79980/5982/9735/5721/2810/5691/9088/995/5685/7468/4172/7336/5690/5684/83990/5686/5695/11200/10213/8345/7534/80010/23198/5983/7979/54908/6396/4683/63967/3018/5699/5714/5702/3014/5905/3619/5708/55166/5692/10393/8290/5704/580/6119
## R-HSA-453279 8318/55388/4605/7153/6241/890/983/81620/891/4174/4171/993/990/7083/898/23594/4998/1163/9134/4175/4173/10926/6502/7298/4609/5111/28227/5688/5709/26271/51053/1869/1029/5698/1719/4067/5693/8317/5427/23649/4176/5713/5557/5721/5691/1871/1031/5685/1019/5558/4172/5690/5684/5686/5695/7027/10213/1875
## R-HSA-69306 8318/55388/11065/27338/890/9837/81620/51659/4174/4171/990/898/23594/4998/9134/4175/4173/2237/10926/6502/5984/84296/5111/5688/64785/5709/51053/1869/5698/1763/5693/8317/5427/23649/4176/5713/5982/5557/5721/5691/1871/5685/5558/4172/5424/5690/5684/5686/5695/10213/23198/5983/7979/5699/5714/5702/9978/5425/5708/5692/10393/54107
## R-HSA-69278 8318/55143/55388/991/2305/9493/1062/4605/9133/10403/7153/23397/6241/11065/220134/22974/4751/79019/55839/27338/890/983/54821/4085/9837/81930/81620/332/64151/9212/51659/10112/6790/891/4174/9232/4001/4171/3161/11004/993/990/5347/701/51512/11130/79682/57405/2491/9700/7083/898/23594/4998/10733/1163/54801/9134/4175/4173/2237/10926/6502/5984/994/9918/7298/1058/84296/3015/699/4609/1063/85236/5111/28227/5688/9688/64785/5709/26271/55055/51053/1869/1029/5698/1763/1719/8970/54892/8357/4067/5693/8317/7277/5427/23649/4176/7112/5713/3930/79980/5982/9735/5557/5721/23310/5691/1871/1031/9088/995/10051/1104/5685/84790/1019/5558/4172/9631/5424/7444/79866/5690/5684/5885/5686/5695/203068/7027/10213/1875/23175/8345/7283/23198/10381/5983/7979/54908/10592/6396/23165/10383/3018/5699/22822/5714/10376/7443/55706/8815/5702/3014/1030/23636/9978/5905/3619/5425/5708/55166/5692/10393/54107
## R-HSA-69206 8318/55388/6241/890/983/81620/891/4174/4171/993/990/7083/898/23594/4998/1163/9134/4175/4173/10926/6502/7298/4609/5111/28227/5688/5709/26271/51053/1869/5698/1719/5693/8317/5427/23649/4176/5713/5557/5721/5691/5685/1019/5558/4172/5690/5684/5686/5695/7027/10213/1875
## R-HSA-2555396 55143/991/1062/9133/10403/11065/220134/79019/55839/27338/983/54821/4085/81930/332/9212/891/9232/4001/11004/5347/701/11130/79682/57405/2491/9700/1058/699/1063/5688/9688/5709/26271/55055/5698/5693/7277/7112/5713/3930/79980/9735/5721/5691/1104/5685/84790/9631/7444/5690/5684/5885/5686/5695/10213/23198/10381/7979/54908/6396/23165/10383/5699/5714/10376/7443/55706/8815/5702/23636/5905/3619/5708/55166/5692/10393/5704/59019.4 Pathway Visualization
ReactomePA implemented the viewPathway() to visualized selected reactome pathway. More general purpose of visualization methods for ORA and GSEA results are provided in the enrichplot package and are documented on Chapter 14.
viewPathway("E2F mediated regulation of DNA replication",
readable = TRUE,
foldChange = geneList)
Figure 9.1: Visualize reactome pathway.