| name | bioconductor-drugtargetinteractions |
| description | Provides utilities for identifying drug-target interactions for sets of small molecule or gene/protein identifiers. The required drug-target interaction information is obained from a local SQLite instance of the ChEMBL database. ChEMBL has been chosen for this purpose, because it provides one of the most comprehensive and best annotatated knowledge resources for drug-target information available in the public domain. |
drugTargetInteractions
Workflows
Standard Workflow
Provides utilities for identifying drug-target interactions for sets of small molecule or gene/protein identifiers. The required drug-target interaction information is obained from a local SQLite instance of the ChEMBL database. ChEMBL has been chosen for this purpose, because it provides one of the most comprehensive and best annotatated knowledge resources for drug-target information available in the public domain.
library(drugTargetInteractions)
chembldb <- system.file("extdata", "chembl_sample.db", package="drugTargetInteractions")
resultsPath <- system.file("extdata", "results", package="drugTargetInteractions")
config <- genConfig(chemblDbPath=chembldb, resultsPath=resultsPath)
downloadUniChem(config=config)
cmpIdMapping(config=config)
queryBy <- list(molType="cmp", idType="chembl_id", ids=c("CHEMBL17", "CHEMBL19"))
qresult1 <- drugTargetAnnot(queryBy, config=config)
Input: A list containing query molecule/protein IDs and a configuration object. Output: A data.frame of drug-target annotations.
When to Use
- Identify drug-target interactions for sets of small molecules or gene/protein identifiers using a local SQLite instance of the ChEMBL database.
- Retrieve UniProt IDs for Ensembl gene IDs using sequence similarity nearest neighbors (SSNNs) via
getUniprotIDs or paralogs via getParalogs.
- Query bioactivity data for compounds or proteins using
drugTargetBioactivity.
When NOT to Use
- For high-throughput de novo molecular docking or 3D structure-based drug design, use packages like
Rcpi or external tools.
- For querying online databases directly without a local SQLite copy of ChEMBL, use direct web API clients.
Data Requirements
- A local SQLite instance of the ChEMBL database (e.g.,
chembl_sample.db for testing).
- Query identifiers formatted as a list with
molType (e.g., "cmp", "protein", "gene"), idType (e.g., "chembl_id", "UniProt_ID", "ensembl_gene_id"), and a character vector of ids.
Key Parameters
- chemblDbPath (NULL): Path to the local ChEMBL SQLite database file passed to
genConfig.
- resultsPath (NULL): Path to the directory where results are stored, passed to
genConfig.
- taxId (9606): Taxonomy ID for organism selection in
getUniprotIDs.
- kt ("ENSEMBL"): Keytype of the input keys in
getUniprotIDs.
- seq_cluster ("UNIREF90"): Sequence similarity level ("UNIREF100", "UNIREF90", "UNIREF50") in
getUniprotIDs.
- id_mapping (c(chembl="chembl_id", pubchem="PubChem_ID", uniprot="UniProt_ID", drugbank="DrugBank_ID")): Mapping vector used in
getDrugTarget.
Best Practices
- Use
genConfig to set up paths to the local ChEMBL SQLite database and output directories before running queries.
- Run
downloadUniChem and cmpIdMapping to download and prepare compound identifier mapping tables.
- Use
getParalogs instead of getUniprotIDs when faster execution and wider evolutionary distances are preferred.
- Combine ID mapping and drug-target annotation steps using the meta function
runDrugTarget_Annot_Bioassay.
Common Pitfalls
- Using the toy database
chembl_sample.db for real analyses: replace the path in genConfig with the path to a full downloaded ChEMBL SQLite database.
- Slow execution of
getUniprotIDs: set chunksize=1 only when tracking query Ensembl gene ID information is strictly required, or use getParalogs as a faster alternative.
- Missing UniProt to Ensembl mappings in final tables: use
tapply to collapse Ensembl IDs when mapping back to UniProt IDs.
Alternatives
biomaRt for general gene/protein annotation and paralog retrieval.UniProt.ws for direct web-based UniProt ID mapping.ensembldb for local genomic and protein feature mapping.
Citations
- Wu et al. 2006, Nucleic Acids Res (The Universal Protein Resource)
- Gaulton et al. 2012, Nucleic Acids Res (ChEMBL database)
- Bento et al. 2014, Nucleic Acids Res (ChEMBL bioactivity database update)
References
