{"doi":"10.1371/journal.pcbi.1000976","title":"The Mycobacterium tuberculosis Drugome and Its Polypharmacological Implications","abstract":"We report a computational approach that integrates structural bioinformatics, molecular modelling and systems biology to construct a drug-target network on a structural proteome-wide scale. The approach has been applied to the genome of Mycobacterium tuberculosis (M.tb), the causative agent of one of today's most widely spread infectious diseases. The resulting drug-target interaction network for all structurally characterized approved drugs bound to putative M.tb receptors, we refer to as the 'TB-drugome'. The TB-drugome reveals that approximately one-third of the drugs examined have the potential to be repositioned to treat tuberculosis and that many currently unexploited M.tb receptors may be chemically druggable and could serve as novel anti-tubercular targets. Furthermore, a detailed analysis of the TB-drugome has shed new light on the controversial issues surrounding drug-target networks [1]-[3]. Indeed, our results support the idea that drug-target networks are inherently modular, and further that any observed randomness is mainly caused by biased target coverage. The TB-drugome (http://funsite.sdsc.edu/drugome/TB) has the potential to be a valuable resource in the development of safe and efficient anti-tubercular drugs. More generally the methodology may be applied to other pathogens of interest with results improving as more of their structural proteomes are determined through the continued efforts of structural biology/genomics.","journal":"PLoS Computational Biology","year":2010,"id":6586,"datarank":4.242593119909067,"base_score":4.6443908991413725,"endowment":4.6443908991413725,"self_citation_contribution":0.6966586348712059,"citation_network_contribution":3.545934485037861,"self_endowment_contribution":0.6966586348712059,"citer_contribution":3.545934485037861,"corpus_percentile":70.30105777054516,"corpus_rank":366,"citation_count":103,"citer_count":86,"citers_with_citation_signal":79,"citers_with_endowment":79,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.6948,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2010-11-04","fair_score":36.25,"fair_percentile":17.963940193491645,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":153,"name":"Li Xie","orcid":"0000-0003-3658-2535","position":1,"is_corresponding":false},{"id":15027,"name":"Kingston H. Fung","orcid":null,"position":2,"is_corresponding":false},{"id":22119,"name":"Richard M. Jackson","orcid":null,"position":3,"is_corresponding":false},{"id":150,"name":"Lei Xie","orcid":"0000-0001-9051-2111","position":4,"is_corresponding":false},{"id":125,"name":"Philip  E. Bourne","orcid":"0000-0002-7618-7292","position":5,"is_corresponding":false},{"id":22116,"name":"Sarah L. Kinnings","orcid":null,"position":0,"is_corresponding":true}],"reference_count":94,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":"21079673","pmcid":"PMC2973814","fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":"gold","license":"cc-by","views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":40.0,"fair_a":67.5,"fair_i":12.5,"fair_r":25.0,"fair_zscore":-0.8106,"fair_rationale":{"fair_score":36.25,"has_llm":true,"dimensions":{"F":{"name":"Findable","score":40.0,"criteria":[{"key":"f_has_doi","label":"Has a persistent DOI","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"DOI present","rationale":null},{"key":"f_repository_presence","label":"Indexed in repositories / literature DBs","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"datacite=0, pmcid=True, pmid=True","rationale":null},{"key":"f_persistent_ids","label":"Resolvable scholarly identifiers (OpenAlex)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no OpenAlex id","rationale":null},{"key":"f_metadata_richness","label":"Rich, machine-readable metadata","kind":"llm","weight":1.0,"fraction":0.0,"signal":null,"rationale":"The paper does not provide or reference machine-readable metadata such as structured, indexable descriptions of the data or code."}]},"A":{"name":"Accessible","score":67.5,"criteria":[{"key":"a_open_access","label":"Open Access / files deposited","kind":"deterministic","weight":1.5,"fraction":1.0,"signal":"Open Access","rationale":null},{"key":"a_retrievable","label":"Free full text retrievable","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"0 OA location(s)","rationale":null},{"key":"a_access_protocol","label":"Clear data/code access protocol","kind":"llm","weight":1.0,"fraction":0.75,"signal":null,"rationale":"The paper provides a clear URL (http://funsite.sdsc.edu/drugome/TB) for accessing the TB-drugome online, but does not describe a specific protocol for automated access or state conditions for data download."}]},"I":{"name":"Interoperable","score":12.5,"criteria":[{"key":"i_linked_data","label":"Linked datasets / DataCite relations","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"linked_datasets=0, datacite=0","rationale":null},{"key":"i_standard_ids","label":"References data via standard accessions","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"accessions=0, trials=0","rationale":null},{"key":"i_standards","label":"Standard formats, vocabularies & identifiers","kind":"llm","weight":1.0,"fraction":0.25,"signal":null,"rationale":"The paper uses standard identifiers (e.g., PDB codes, gene names) and formats (e.g., SMILES, PDB files) but does not specify use of controlled vocabularies, standardized data exchange formats, or persistent identifiers beyond DOIs."}]},"R":{"name":"Reusable","score":25.0,"criteria":[{"key":"r_license","label":"Clear, open reuse license","kind":"deterministic","weight":1.5,"fraction":0.0,"signal":"no license","rationale":null},{"key":"r_downloads","label":"Demonstrated reuse (downloads)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"downloads=0","rationale":null},{"key":"r_version","label":"Versioned / maintained","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no version chain","rationale":null},{"key":"r_dataset","label":"Classified as a data resource","kind":"deterministic","weight":0.5,"fraction":1.0,"signal":"is_dataset","rationale":null},{"key":"r_reusability","label":"Data-availability statement, license & reproducibility","kind":"llm","weight":2.0,"fraction":0.333,"signal":null,"rationale":"The paper states open-access under Creative Commons Attribution License but lacks a formal data-availability statement, explicit license for the data/code, and does not provide sufficient details (e.g., scripts, raw outputs) for full reproducibility."}]}},"suggestions":["Provide structured, machine-readable metadata (e.g., as RDF/JSON-LD) describing the TB-drugome dataset, including funding, license, and provenance.","Publish the complete list of drug-target interactions (including scoring thresholds and docking results) in a standardized format such as TSV or CSV with a data dictionary.","Add a formal data-availability statement that specifies the license (e.g., CC0 or ODC-BY) for the dataset and code, and deposit the dataset in a persistent repository (e.g., Zenodo) with a DOI.","Describe the exact version of the software and parameters used (SMAP, eHiTS) so that the analysis can be reproduced; consider sharing the exact command lines or workflows.","Include a machine-readable access protocol (e.g., REST API endpoint or SPARQL endpoint) for the TB-drugome database to improve automated access."],"model":"deepseek/deepseek-v4-flash","agent_version":"fair_agent_v2","fulltext_source":"epmc_xml"},"fair_model":"deepseek/deepseek-v4-flash","fair_agent_version":"fair_agent_v2","fair_fulltext_source":"epmc_xml","fair_has_llm":true,"fair_computed_at":"2026-06-18T00:39:37.530219Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}