Chapter 14 Useful utilities

14.1 bitr: Biological Id TranslatoR

clusterProfiler provides bitr and bitr_kegg for converting ID types. Both bitr and bitr_kegg support many species including model and many non-model organisms.

x <- c("GPX3",  "GLRX",   "LBP",   "CRYAB", "DEFB1", "HCLS1",   "SOD2",   "HSPA2",
       "ORM1",  "IGFBP1", "PTHLH", "GPC3",  "IGFBP3","TOB1",    "MITF",   "NDRG1",
       "NR1H4", "FGFR3",  "PVR",   "IL6",   "PTPRM", "ERBB2",   "NID2",   "LAMB1",
       "COMP",  "PLS3",   "MCAM",  "SPP1",  "LAMC1", "COL4A2",  "COL4A1", "MYOC",
       "ANXA4", "TFPI2",  "CST6",  "SLPI",  "TIMP2", "CPM",     "GGT1",   "NNMT",
       "MAL",   "EEF1A2", "HGD",   "TCN2",  "CDA",   "PCCA",    "CRYM",   "PDXK",
       "STC1",  "WARS",  "HMOX1", "FXYD2", "RBP4",   "SLC6A12", "KDELR3", "ITM2B")
eg = bitr(x, fromType="SYMBOL", toType="ENTREZID", OrgDb="org.Hs.eg.db")
head(eg)
##   SYMBOL ENTREZID
## 1   GPX3     2878
## 2   GLRX     2745
## 3    LBP     3929
## 4  CRYAB     1410
## 5  DEFB1     1672
## 6  HCLS1     3059

User should provides an annotation package, both fromType and toType can accept any types that supported.

User can use keytypes to list all supporting types.

library(org.Hs.eg.db)
keytypes(org.Hs.eg.db)
##  [1] "ACCNUM"       "ALIAS"        "ENSEMBL"     
##  [4] "ENSEMBLPROT"  "ENSEMBLTRANS" "ENTREZID"    
##  [7] "ENZYME"       "EVIDENCE"     "EVIDENCEALL" 
## [10] "GENENAME"     "GO"           "GOALL"       
## [13] "IPI"          "MAP"          "OMIM"        
## [16] "ONTOLOGY"     "ONTOLOGYALL"  "PATH"        
## [19] "PFAM"         "PMID"         "PROSITE"     
## [22] "REFSEQ"       "SYMBOL"       "UCSCKG"      
## [25] "UNIGENE"      "UNIPROT"

We can translate from one type to other types.

ids <- bitr(x, fromType="SYMBOL", toType=c("UNIPROT", "ENSEMBL"), OrgDb="org.Hs.eg.db")
head(ids)
##   SYMBOL    UNIPROT         ENSEMBL
## 1   GPX3     P22352 ENSG00000211445
## 2   GLRX A0A024RAM2 ENSG00000173221
## 3   GLRX     P35754 ENSG00000173221
## 4    LBP     P18428 ENSG00000129988
## 5    LBP     Q8TCF0 ENSG00000129988
## 6  CRYAB     P02511 ENSG00000109846

For GO analysis, user don’t need to convert ID, all ID type provided by OrgDb can be used in groupGO, enrichGO and gseGO by specifying keyType parameter.

14.1.1 bitr_kegg: converting biological IDs using KEGG API

data(gcSample)
hg <- gcSample[[1]]
head(hg)
## [1] "4597"  "7111"  "5266"  "2175"  "755"   "23046"
eg2np <- bitr_kegg(hg, fromType='kegg', toType='ncbi-proteinid', organism='hsa')
head(eg2np)
##    kegg ncbi-proteinid
## 1 10001      NP_005457
## 2 10209      NP_005792
## 3 10232      NP_037536
## 4 10324      NP_006054
## 5 10411   NP_001092002
## 6 10614      NP_006451

The ID type (both fromType & toType) should be one of ‘kegg’, ‘ncbi-geneid’, ‘ncbi-proteinid’ or ‘uniprot’. The ‘kegg’ is the primary ID used in KEGG database. The data source of KEGG was from NCBI. A rule of thumb for the ‘kegg’ ID is entrezgene ID for eukaryote species and Locus ID for prokaryotes.

Many prokaryote species don’t have entrezgene ID available. For example we can check the gene information of ece:Z5100 in http://www.genome.jp/dbget-bin/www_bget?ece:Z5100, which have NCBI-ProteinID and UnitProt links in the Other DBs Entry, but not NCBI-GeneID.

If we try to convert Z5100 to ncbi-geneid, bitr_kegg will throw error of ncbi-geneid is not supported.

bitr_kegg("Z5100", fromType="kegg", toType='ncbi-geneid', organism='ece')
## Error in KEGG_convert(fromType, toType, organism) :
## ncbi-geneid is not supported for ece ...

We can of course convert it to ncbi-proteinid and uniprot:

bitr_kegg("Z5100", fromType="kegg", toType='ncbi-proteinid', organism='ece')
##    kegg ncbi-proteinid
## 1 Z5100       AAG58814
bitr_kegg("Z5100", fromType="kegg", toType='uniprot', organism='ece')
##    kegg    uniprot
## 1 Z5100 A0A3G4X4E3

14.2 setReadable: translating gene IDs to human readable symbols

Some of the functions, especially those internally supported for DO, GO, and Reactome Pathway, support a parameter, readable. If readable = TRUE, all the gene IDs will be translated to gene symbols. The readable parameter is not available for enrichment analysis of KEGG or using user’s own annotation. KEGG analysis using enrichKEGG and gseKEGG, internally query annotation information from KEEGG database and thus support all species if it is available in the KEGG database. However, KEGG database doesn’t provide gene ID to symbol mapping information. For analysis using user’s own annotation data, we even don’t know what species is in analyzed. Translating gene IDs to gene symbols is partly supported using the setReadable function if and only if there is an OrgDb available.

library(org.Hs.eg.db)
library(clusterProfiler)

data(geneList, package="DOSE")
de <- names(geneList)[1:100]
x <- enrichKEGG(de)
## The geneID column is ENTREZID
head(x, 3)
##                ID         Description GeneRatio  BgRatio
## hsa04110 hsa04110          Cell cycle      8/48 124/7860
## hsa04218 hsa04218 Cellular senescence      7/48 160/7860
## hsa04114 hsa04114      Oocyte meiosis      6/48 125/7860
##                pvalue     p.adjust       qvalue
## hsa04110 6.804611e-07 7.689211e-05 7.091121e-05
## hsa04218 4.636787e-05 2.619785e-03 2.416010e-03
## hsa04114 1.018994e-04 3.838210e-03 3.539662e-03
##                                        geneID Count
## hsa04110 8318/991/9133/890/983/4085/7272/1111     8
## hsa04218    2305/4605/9133/890/983/51806/1111     7
## hsa04114         991/9133/983/4085/51806/6790     6
y <- setReadable(x, OrgDb = org.Hs.eg.db, keyType="ENTREZID")
## The geneID column is translated to symbol
head(y, 3)
##                ID         Description GeneRatio  BgRatio
## hsa04110 hsa04110          Cell cycle      8/48 124/7860
## hsa04218 hsa04218 Cellular senescence      7/48 160/7860
## hsa04114 hsa04114      Oocyte meiosis      6/48 125/7860
##                pvalue     p.adjust       qvalue
## hsa04110 6.804611e-07 7.689211e-05 7.091121e-05
## hsa04218 4.636787e-05 2.619785e-03 2.416010e-03
## hsa04114 1.018994e-04 3.838210e-03 3.539662e-03
##                                                 geneID
## hsa04110 CDC45/CDC20/CCNB2/CCNA2/CDK1/MAD2L1/TTK/CHEK1
## hsa04218     FOXM1/MYBL2/CCNB2/CCNA2/CDK1/CALML5/CHEK1
## hsa04114          CDC20/CCNB2/CDK1/MAD2L1/CALML5/AURKA
##          Count
## hsa04110     8
## hsa04218     7
## hsa04114     6

For those functions that internally support readable parameter, user can also use setReadable for translating gene IDs.