Downloading DSigDB and cache

Reference:
Yoo M, Shin J, Kim J, Ryall KA, Lee K, Lee S, Jeon M, Kang J, Tan AC. (2015). DSigDB: Drug Signatures Database for Gene Set Analysis. Bioinformatics. 31(18): 3069-3071. [PMID: 25990557].

library(BiocFileCache)
## Loading required package: dbplyr
url <- "http://dsigdb.tanlab.org/Downloads/DSigDB_All_detailed.txt"
bfc <- BiocFileCache()
path <- bfcrpath(bfc, url)
## adding rname 'http://dsigdb.tanlab.org/Downloads/DSigDB_All_detailed.txt'

Use clusterProfiler::enricher for the enrichment analysis

library(clusterProfiler)
dsig <- readr::read_tsv(path)
## Warning: One or more parsing issues, see `problems()` for details
drug2gene=dsig[, c("Drug", "Gene")]

## Example of ERCC genes
erccs <- c("ERCC1","ERCC2","ERCC3","ERCC4","ERCC5","ERCC6","ERCC8")
res <- enricher(gene = erccs, TERM2GENE=drug2gene)

knitr::kable(
    res@result[1:5,],
    row.names=FALSE
)
ID Description GeneRatio BgRatio pvalue p.adjust qvalue geneID Count
Cyclohexanecarboxamide, 4-(1-aminoethyl)-N-4-pyridinyl-, trans- Cyclohexanecarboxamide, 4-(1-aminoethyl)-N-4-pyridinyl-, trans- 3/7 52/19647 6.00e-07 0.0000352 0.0000153 ERCC1/ERCC2/ERCC5 3
Veliparib Veliparib 2/7 20/19647 2.06e-05 0.0005977 0.0002604 ERCC1/ERCC4 2
Chloroethylene Chloroethylene 2/7 32/19647 5.37e-05 0.0009335 0.0004066 ERCC2/ERCC4 2
leucovorin leucovorin 2/7 35/19647 6.44e-05 0.0009335 0.0004066 ERCC1/ERCC2 2
Myristicin Myristicin 2/7 43/19647 9.76e-05 0.0011319 0.0004930 ERCC1/ERCC2 2

Plot using various functions

dotplot(res)

cnetplot(res)

Examining renal cell carcinoma

library(org.Hs.eg.db)
keggPathways <- org.Hs.egPATH2EG
mappedKeys <- mappedkeys(keggPathways)
keggList <- as.list(keggPathways[mappedKeys])
symbolRCC <- AnnotationDbi::select(x=org.Hs.eg.db, keys=keggList$`05211`, keytype="ENTREZID", columns = "SYMBOL")$SYMBOL

resRCC <- enricher(gene = symbolRCC, TERM2GENE=drug2gene)

knitr::kable(
    resRCC@result[1:20,],
    row.names=FALSE
)
ID Description GeneRatio BgRatio pvalue p.adjust qvalue geneID Count
LY 294002 LY 294002 19/66 241/19647 0 0 0 AKT1/AKT2/ETS1/HIF1A/JUN/PDGFB/PIK3CA/PIK3CB/PIK3CD/PIK3CG/MAPK1/MAPK3/MAP2K1/RAF1/RAP1A/SLC2A1/TGFB1/VEGFA/AKT3 19
diclofenac diclofenac 22/66 477/19647 0 0 0 AKT1/AKT2/ARAF/ARNT/BRAF/EPAS1/GAB1/HIF1A/HRAS/JUN/KRAS/NRAS/PAK2/PIK3CA/PIK3CD/PIK3R1/PIK3R2/SOS1/SOS2/TGFA/VEGFA/PIK3R3 22
PD 98059 PD 98059 18/66 274/19647 0 0 0 AKT1/AKT2/ARNT/EP300/HGF/HIF1A/JUN/PDGFB/MAPK1/MAPK3/MAP2K1/MAP2K2/RAF1/SLC2A1/TGFA/TGFB1/VEGFA/AKT3 18
bisindolylmaleimide i bisindolylmaleimide i 12/66 79/19647 0 0 0 AKT1/AKT2/HGF/JUN/MAPK1/MAPK3/MAP2K1/MAP2K2/RAC1/RAP1A/VEGFA/AKT3 12
PI-103 PI-103 10/66 41/19647 0 0 0 AKT1/HIF1A/PIK3CA/PIK3CB/PIK3CD/PIK3CG/MAPK1/MAPK3/MAP2K1/MAP2K2 10
Luronit Luronit 9/66 35/19647 0 0 0 EP300/GAB1/JUN/PIK3CA/MAPK1/MAPK3/MAP2K1/MAP2K2/VEGFA 9
rapamycin rapamycin 17/66 394/19647 0 0 0 AKT1/AKT2/HIF1A/HRAS/PAK3/PDGFB/PIK3CA/PIK3CD/PIK3R1/MAPK1/MAPK3/MAP2K1/MAP2K2/RAC1/RAF1/TGFB1/VEGFA 17
Andrographolide Andrographolide 9/66 43/19647 0 0 0 AKT1/HIF1A/JUN/MAPK1/MAPK3/RAF1/TGFB1/VEGFA/EGLN1 9
Phorbol 12-myristate 13-acetate Phorbol 12-myristate 13-acetate 18/66 483/19647 0 0 0 AKT1/CREBBP/HGF/HIF1A/HRAS/JUN/KRAS/PAK3/PDGFB/MAPK1/MAPK3/MAP2K1/MAP2K2/RAC1/TGFB1/TGFB2/VEGFA/RBX1 18
lovastatin lovastatin 12/66 157/19647 0 0 0 AKT1/CDC42/HRAS/JUN/KRAS/NRAS/MAPK1/MAPK3/RAC1/RAF1/RAP1A/TGFB1 12
U-0126 U-0126 7/66 19/19647 0 0 0 AKT1/AKT2/MAPK1/MAP2K1/MAP2K2/RAF1/AKT3 7
NVP-TAE684 NVP-TAE684 13/66 223/19647 0 0 0 AKT1/GAB1/HGF/MET/PAK1/PAK3/MAPK1/MAPK3/MAP2K1/MAP2K2/TGFA/PAK4/PAK6 13
Canertinib dihydrochloride Canertinib dihydrochloride 6/66 12/19647 0 0 0 AKT1/AKT2/MAPK1/MAPK3/VEGFA/AKT3 6
SB 202190 SB 202190 10/66 103/19647 0 0 0 AKT1/AKT2/HIF1A/JUN/MAPK1/MAPK3/TGFA/TGFB1/VEGFA/AKT3 10
Geranylgeranyl pyrophosphate Geranylgeranyl pyrophosphate 8/66 44/19647 0 0 0 AKT1/HRAS/PDGFB/MAPK1/MAPK3/RAC1/TGFB1/VEGFA 8
Go 6976 Go 6976 10/66 105/19647 0 0 0 AKT1/AKT2/HRAS/JUN/MAPK1/MAPK3/VEGFA/AKT3/PAK4/PAK6 10
Trametinib Trametinib 6/66 15/19647 0 0 0 AKT1/JUN/MAPK1/MAPK3/MAP2K1/MAP2K2 6
N-Acetyl-L-cysteine N-Acetyl-L-cysteine 15/66 442/19647 0 0 0 AKT1/ARNT/EP300/ETS1/HGF/HIF1A/JUN/KRAS/MAPK1/MAPK3/MAP2K1/MAP2K2/RAC1/TGFB1/VEGFA 15
wortmannin wortmannin 12/66 233/19647 0 0 0 AKT1/EPAS1/HIF1A/PIK3CA/PIK3CB/PIK3CD/PIK3CG/PIK3R1/MAPK1/MAPK3/RAP1A/VEGFA 12
Perifosine Perifosine 6/66 18/19647 0 0 0 AKT1/AKT2/MAPK1/MAPK3/MAP2K1/AKT3 6 
heatplot(resRCC)