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.
Chapter overview
Questions Which curated Reactome pathways are over-represented or show coordinated signal in a ranked gene profile?
Input Entrez IDs from a supported organism; GSEA uses a named ranked vector.
Methods Pathway ORA and GSEA, Reactome-specific pathway visualization, and comparisons across gene clusters.
Main functions enrichPathway(), gsePathway(), viewPathway(), and compareCluster().
Output enrichResult / gseaResult objects and optional Reactome pathway diagrams.
Main limitations The supported species set is limited; ID conversion and Reactome release affect coverage. Confirm species and mapping before interpreting absent pathways.
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()
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.
Reactome is a remote service that can fail transiently, so the calls in this chapter are wrapped in the retry() helper defined in _common.R; readers who prefer a single attempt can simply drop the wrapper in their own analysis.
library (ReactomePA)data (geneList, package= "DOSE" <- names (geneList)[abs (geneList) > 1.5 ]head (de)
[1] "4312" "8318" "10874" "55143" "55388" "991"
<- retry (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-68882 R-HSA-68882
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-68882 Mitotic Anaphase
GeneRatio BgRatio RichFactor FoldEnrichment oddsRatio zScore
R-HSA-69620 38/342 292/11287 0.1301370 4.294901 5.261319 10.083502
R-HSA-69618 22/342 113/11287 0.1946903 6.425348 8.200137 10.245607
R-HSA-2500257 23/342 129/11287 0.1782946 5.884242 7.372597 9.862206
R-HSA-141424 20/342 96/11287 0.2083333 6.875609 8.882805 10.219491
R-HSA-141444 20/342 96/11287 0.2083333 6.875609 8.882805 10.219491
R-HSA-68882 28/342 225/11287 0.1244444 4.107031 4.865078 8.321376
pvalue p.adjust qvalue
R-HSA-69620 1.988463e-14 1.805524e-11 1.805524e-11
R-HSA-69618 2.386464e-12 1.083455e-09 1.083455e-09
R-HSA-2500257 5.135365e-12 1.182511e-09 1.182511e-09
R-HSA-141424 6.511625e-12 1.182511e-09 1.182511e-09
R-HSA-141444 6.511625e-12 1.182511e-09 1.182511e-09
R-HSA-68882 1.865374e-10 2.686794e-08 2.686794e-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-68882 CDCA8/CDC20/CENPE/CCNB2/NDC80/UBE2C/SKA1/CENPM/CENPN/UBE2S/CDK1/ERCC6L/MAD2L1/KIF18A/BIRC5/AURKB/CCNB1/PTTG1/LMNB1/KIF2C/PLK1/BUB1B/ZWINT/CENPU/SPC25/CENPI/ESPL1/TAOK1
Count
R-HSA-69620 38
R-HSA-69618 22
R-HSA-2500257 23
R-HSA-141424 20
R-HSA-141444 20
R-HSA-68882 28
Reactome pathway gene set enrichment analysis
<- retry (gsePathway (geneList,pvalueCutoff = 0.2 ,pAdjustMethod = "BH" , verbose = FALSE ))head (y)
ID Description setSize
R-HSA-453279 R-HSA-453279 Mitotic G1 phase and G1/S transition 132
R-HSA-69620 R-HSA-69620 Cell Cycle Checkpoints 238
R-HSA-69206 R-HSA-69206 G1/S Transition 114
R-HSA-69278 R-HSA-69278 Cell Cycle, Mitotic 451
R-HSA-68882 R-HSA-68882 Mitotic Anaphase 189
R-HSA-69481 R-HSA-69481 G2/M Checkpoints 125
enrichmentScore NES pvalue p.adjust qvalue rank
R-HSA-453279 0.7117138 3.021588 1e-10 4.648571e-09 4.648571e-09 1155
R-HSA-69620 0.6508576 2.996937 1e-10 4.648571e-09 4.648571e-09 1905
R-HSA-69206 0.7163844 2.991551 1e-10 4.648571e-09 4.648571e-09 1155
R-HSA-69278 0.6094048 2.989889 1e-10 4.648571e-09 4.648571e-09 1769
R-HSA-68882 0.6518659 2.935094 1e-10 4.648571e-09 4.648571e-09 1857
R-HSA-69481 0.6968899 2.928007 1e-10 4.648571e-09 4.648571e-09 1905
leading_edge
R-HSA-453279 tags=43%, list=9%, signal=40%
R-HSA-69620 tags=42%, list=15%, signal=36%
R-HSA-69206 tags=45%, list=9%, signal=41%
R-HSA-69278 tags=36%, list=14%, signal=32%
R-HSA-68882 tags=40%, list=15%, signal=35%
R-HSA-69481 tags=50%, list=15%, signal=43%
core_enrichment
R-HSA-453279 8318/55388/4605/7153/6241/890/983/81620/891/4174/4171/993/990/7083/898/23594/4998/1163/9134/4175/4173/10926/6502/7298/4609/5111/28227/5688/5709/26271/51053/1869/1029/1719/4067/5693/8317/5427/23649/4176/5713/11047/5557/5691/1871/1031/5685/1019/5558/4172/5690/5684/5686/5695/7027/10213/1875
R-HSA-69620 8318/55143/55388/991/1062/9133/10403/11065/220134/79019/55839/27338/890/983/54821/4085/81930/332/9212/1111/891/4174/4171/11004/993/990/5347/701/51512/9156/11130/79682/57405/2491/898/23594/4998/9134/4175/4173/10926/5984/1058/699/1063/85236/5688/5709/55055/641/1029/1763/8970/5693/8317/4176/5713/79980/5982/9735/11047/2810/5691/9088/995/5685/7468/4172/7336/5690/5684/83990/5686/5695/11200/10213/8345/7534/80010/5983/7979/54908/6396/4683/63967/3018/5714/5702/3014/9978/5905/3619/5708/55166/5692/10393/8290/5704/580/6119
R-HSA-69206 8318/55388/6241/890/983/81620/891/4174/4171/993/990/7083/898/23594/4998/1163/9134/4175/4173/10926/6502/7298/4609/5111/28227/5688/5709/26271/51053/1869/1719/5693/8317/5427/23649/4176/5713/11047/5557/5691/5685/1019/5558/4172/5690/5684/5686/5695/7027/10213/1875
R-HSA-69278 8318/55143/55388/991/2305/9493/1062/4605/9133/10403/7153/23397/6241/11065/55355/220134/22974/4751/79019/55839/27338/890/983/54821/4085/9837/81930/81620/332/64151/9212/51659/10112/6790/891/4174/9232/4001/4171/3161/11004/993/990/5347/701/51512/11130/79682/57405/2491/9700/7083/898/23594/4998/10733/1163/54801/9134/4175/4173/2237/10926/6502/5984/994/9918/7298/1058/84296/699/4609/1063/85236/5111/28227/5688/9688/64785/5709/26271/55055/51053/1869/1029/1763/1719/8970/54892/8357/4067/5693/8317/7277/5427/23649/4176/7112/5713/3930/79980/5982/9735/55732/11047/5557/23310/5691/1871/1031/80086/9088/995/10051/1104/5685/84790/1019/5558/4172/9631/5424/7444/79866/5690/5684/5885/5686/5695/203068/7027/10213/1875/23175/8345/7283/10381/5983/7979/54908/10592/6396/23165/10383/3018/22822/5714/10376/7443/55706/8815/5702/3014/1030/23636/9978/5905/3619/5425/5708/55166/5692/10393/54107
R-HSA-68882 55143/991/1062/9133/10403/11065/220134/79019/55839/27338/983/54821/4085/81930/332/9212/891/9232/4001/11004/5347/701/11130/79682/57405/2491/9700/1058/699/1063/5688/9688/5709/55055/5693/7277/7112/5713/3930/79980/9735/11047/5691/80086/1104/5685/84790/9631/7444/5690/5684/5885/5686/5695/10213/10381/7979/54908/6396/23165/10383/5714/10376/7443/55706/8815/5702/23636/5905/3619/5708/55166/5692/10393/5704/5901
R-HSA-69481 8318/55388/9133/890/983/1111/891/4174/4171/993/990/51512/9156/23594/4998/4175/4173/10926/5984/85236/5688/5709/641/1763/8970/5693/8317/4176/5713/5982/11047/2810/5691/9088/995/5685/7468/4172/7336/5690/5684/83990/5686/5695/11200/10213/8345/7534/80010/5983/7979/4683/63967/3018/5714/5702/3014/5708/5692/8290/5704/580/6119
log2err
R-HSA-453279 NaN
R-HSA-69620 NaN
R-HSA-69206 NaN
R-HSA-69278 NaN
R-HSA-68882 NaN
R-HSA-69481 NaN
Pathway Visualization
ReactomePA implemented the viewPathway() to visualize selected reactome pathways. More general purpose visualization methods for ORA and GSEA results are provided in the enrichplot package and are documented in Chapter 26 Figure 12.1 for an example.
retry (viewPathway ("E2F mediated regulation of DNA replication" ,readable = TRUE , foldChange = geneList))
References
Yu, Guangchuang, and Qing-Yu He. 2016.
“ReactomePA : An r/Bioconductor Package for Reactome Pathway Analysis and Visualization.” Molecular BioSystems 12 (2): 477–79.
https://doi.org/10.1039/C5MB00663E .
