{"id":"https://openalex.org/W7124180940","doi":"https://doi.org/10.1093/bioinformatics/btag008","title":"A case-based explainable graph neural network framework for mechanistic drug repositioning","display_name":"A case-based explainable graph neural network framework for mechanistic drug repositioning","publication_year":2026,"publication_date":"2026-01-14","ids":{"openalex":"https://openalex.org/W7124180940","doi":"https://doi.org/10.1093/bioinformatics/btag008","pmid":"https://pubmed.ncbi.nlm.nih.gov/41533699"},"language":"en","primary_location":{"id":"doi:10.1093/bioinformatics/btag008","is_oa":true,"landing_page_url":"https://doi.org/10.1093/bioinformatics/btag008","pdf_url":null,"source":{"id":"https://openalex.org/S52395412","display_name":"Bioinformatics","issn_l":"1367-4803","issn":["1367-4803","1367-4811"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Bioinformatics","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.1093/bioinformatics/btag008","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5049333597","display_name":"Carolina Gonzalez-Cavazos","orcid":"https://orcid.org/0000-0001-9615-7157"},"institutions":[{"id":"https://openalex.org/I123431417","display_name":"Scripps Research Institute","ror":"https://ror.org/02dxx6824","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I123431417"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Adriana Carolina Gonzalez-Cavazos","raw_affiliation_strings":["Department of Integrative Structural and Computational Biology, The Scripps Research Institute , La Jolla, CA 92037,"],"affiliations":[{"raw_affiliation_string":"Department of Integrative Structural and Computational Biology, The Scripps Research Institute , La Jolla, CA 92037,","institution_ids":["https://openalex.org/I123431417"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5012527135","display_name":"Roger Tu","orcid":"https://orcid.org/0000-0002-7899-1604"},"institutions":[{"id":"https://openalex.org/I123431417","display_name":"Scripps Research Institute","ror":"https://ror.org/02dxx6824","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I123431417"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Roger Tu","raw_affiliation_strings":["Department of Integrative Structural and Computational Biology, The Scripps Research Institute , La Jolla, CA 92037,"],"affiliations":[{"raw_affiliation_string":"Department of Integrative Structural and Computational Biology, The Scripps Research Institute , La Jolla, CA 92037,","institution_ids":["https://openalex.org/I123431417"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Meghamala Sinha","orcid":"https://orcid.org/0000-0002-6422-3313"},"institutions":[{"id":"https://openalex.org/I123431417","display_name":"Scripps Research Institute","ror":"https://ror.org/02dxx6824","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I123431417"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Meghamala Sinha","raw_affiliation_strings":["Department of Integrative Structural and Computational Biology, The Scripps Research Institute , La Jolla, CA 92037,"],"affiliations":[{"raw_affiliation_string":"Department of Integrative Structural and Computational Biology, The Scripps Research Institute , La Jolla, CA 92037,","institution_ids":["https://openalex.org/I123431417"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5045408201","display_name":"Andrew I. Su","orcid":"https://orcid.org/0000-0002-9859-4104"},"institutions":[{"id":"https://openalex.org/I123431417","display_name":"Scripps Research Institute","ror":"https://ror.org/02dxx6824","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I123431417"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Andrew I Su","raw_affiliation_strings":["Department of Integrative Structural and Computational Biology, The Scripps Research Institute , La Jolla, CA 92037,"],"affiliations":[{"raw_affiliation_string":"Department of Integrative Structural and Computational Biology, The Scripps Research Institute , La Jolla, CA 92037,","institution_ids":["https://openalex.org/I123431417"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":4,"corresponding_author_ids":["https://openalex.org/A5049333597"],"corresponding_institution_ids":["https://openalex.org/I123431417"],"apc_list":{"value":3618,"currency":"USD","value_usd":3618},"apc_paid":{"value":3618,"currency":"USD","value_usd":3618},"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.1245757,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"42","issue":"2","first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.91839998960495,"subfield":{"id":"https://openalex.org/subfields/1703","display_name":"Computational Theory and Mathematics"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.91839998960495,"subfield":{"id":"https://openalex.org/subfields/1703","display_name":"Computational Theory and Mathematics"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10887","display_name":"Bioinformatics and Genomic Networks","score":0.02319999970495701,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11273","display_name":"Advanced Graph Neural Networks","score":0.021800000220537186,"subfield":{"id":"https://openalex.org/subfields/1702","display_name":"Artificial Intelligence"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/leverage","display_name":"Leverage (statistics)","score":0.8355000019073486},{"id":"https://openalex.org/keywords/graph","display_name":"Graph","score":0.5415999889373779},{"id":"https://openalex.org/keywords/knowledge-graph","display_name":"Knowledge graph","score":0.5374000072479248},{"id":"https://openalex.org/keywords/drug-repositioning","display_name":"Drug repositioning","score":0.46000000834465027},{"id":"https://openalex.org/keywords/artificial-neural-network","display_name":"Artificial neural network","score":0.40290001034736633},{"id":"https://openalex.org/keywords/deep-neural-networks","display_name":"Deep neural networks","score":0.3930000066757202}],"concepts":[{"id":"https://openalex.org/C153083717","wikidata":"https://www.wikidata.org/wiki/Q6535263","display_name":"Leverage (statistics)","level":2,"score":0.8355000019073486},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.8144999742507935},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.5508999824523926},{"id":"https://openalex.org/C132525143","wikidata":"https://www.wikidata.org/wiki/Q141488","display_name":"Graph","level":2,"score":0.5415999889373779},{"id":"https://openalex.org/C2987255567","wikidata":"https://www.wikidata.org/wiki/Q33002955","display_name":"Knowledge graph","level":2,"score":0.5374000072479248},{"id":"https://openalex.org/C119857082","wikidata":"https://www.wikidata.org/wiki/Q2539","display_name":"Machine learning","level":1,"score":0.5102999806404114},{"id":"https://openalex.org/C103637391","wikidata":"https://www.wikidata.org/wiki/Q5308921","display_name":"Drug repositioning","level":3,"score":0.46000000834465027},{"id":"https://openalex.org/C50644808","wikidata":"https://www.wikidata.org/wiki/Q192776","display_name":"Artificial neural network","level":2,"score":0.40290001034736633},{"id":"https://openalex.org/C2984842247","wikidata":"https://www.wikidata.org/wiki/Q197536","display_name":"Deep neural networks","level":3,"score":0.3930000066757202},{"id":"https://openalex.org/C64903051","wikidata":"https://www.wikidata.org/wiki/Q2198549","display_name":"Drug development","level":3,"score":0.3041999936103821},{"id":"https://openalex.org/C149364088","wikidata":"https://www.wikidata.org/wiki/Q185917","display_name":"Translation (biology)","level":4,"score":0.3027999997138977},{"id":"https://openalex.org/C2777904410","wikidata":"https://www.wikidata.org/wiki/Q7397","display_name":"Software","level":2,"score":0.27399998903274536},{"id":"https://openalex.org/C28225019","wikidata":"https://www.wikidata.org/wiki/Q4915005","display_name":"Biological network","level":2,"score":0.2632000148296356},{"id":"https://openalex.org/C112972136","wikidata":"https://www.wikidata.org/wiki/Q7595718","display_name":"Stability (learning theory)","level":2,"score":0.2524000108242035}],"mesh":[{"descriptor_ui":"D000098422","descriptor_name":"Graph Neural Networks","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000098422","descriptor_name":"Graph Neural Networks","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000098422","descriptor_name":"Graph Neural Networks","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000465","descriptor_name":"Algorithms","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000465","descriptor_name":"Algorithms","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000465","descriptor_name":"Algorithms","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016571","descriptor_name":"Neural Networks, Computer","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D016571","descriptor_name":"Neural Networks, Computer","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D016571","descriptor_name":"Neural Networks, Computer","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D019295","descriptor_name":"Computational Biology","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D019295","descriptor_name":"Computational Biology","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D019295","descriptor_name":"Computational Biology","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D058492","descriptor_name":"Drug Repositioning","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D058492","descriptor_name":"Drug Repositioning","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D058492","descriptor_name":"Drug Repositioning","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true}],"locations_count":4,"locations":[{"id":"doi:10.1093/bioinformatics/btag008","is_oa":true,"landing_page_url":"https://doi.org/10.1093/bioinformatics/btag008","pdf_url":null,"source":{"id":"https://openalex.org/S52395412","display_name":"Bioinformatics","issn_l":"1367-4803","issn":["1367-4803","1367-4811"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Bioinformatics","raw_type":"journal-article"},{"id":"pmid:41533699","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/41533699","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Bioinformatics (Oxford, England)","raw_type":null},{"id":"pmh:oai:europepmc.org:11699319","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12891909","pdf_url":null,"source":{"id":"https://openalex.org/S4306400806","display_name":"Europe PMC (PubMed Central)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1303153112","host_organization_name":"European Bioinformatics Institute","host_organization_lineage":["https://openalex.org/I1303153112"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Text"},{"id":"pmh:oai:pubmedcentral.nih.gov:12891909","is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12891909/","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Bioinformatics","raw_type":"Text"}],"best_oa_location":{"id":"doi:10.1093/bioinformatics/btag008","is_oa":true,"landing_page_url":"https://doi.org/10.1093/bioinformatics/btag008","pdf_url":null,"source":{"id":"https://openalex.org/S52395412","display_name":"Bioinformatics","issn_l":"1367-4803","issn":["1367-4803","1367-4811"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Bioinformatics","raw_type":"journal-article"},"sustainable_development_goals":[],"awards":[{"id":"https://openalex.org/G5510080918","display_name":null,"funder_award_id":"R01AG066750","funder_id":"https://openalex.org/F4320337337","funder_display_name":"National Institute on Aging"}],"funders":[{"id":"https://openalex.org/F4320337337","display_name":"National Institute on Aging","ror":"https://ror.org/049v75w11"},{"id":"https://openalex.org/F4320337472","display_name":"National Center for Advancing Translational Sciences","ror":"https://ror.org/04pw6fb54"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":29,"referenced_works":["https://openalex.org/W1988752447","https://openalex.org/W2023103902","https://openalex.org/W2024774962","https://openalex.org/W2034769638","https://openalex.org/W2047703003","https://openalex.org/W2083258699","https://openalex.org/W2147959051","https://openalex.org/W2162042267","https://openalex.org/W2621266345","https://openalex.org/W2886454401","https://openalex.org/W2896002881","https://openalex.org/W2944545583","https://openalex.org/W2949311246","https://openalex.org/W3042221936","https://openalex.org/W3093030756","https://openalex.org/W3156482783","https://openalex.org/W4226138412","https://openalex.org/W4281620605","https://openalex.org/W4300450827","https://openalex.org/W4306385868","https://openalex.org/W4308559752","https://openalex.org/W4318983406","https://openalex.org/W4377231792","https://openalex.org/W4381839562","https://openalex.org/W4385330534","https://openalex.org/W4386802074","https://openalex.org/W4401730694","https://openalex.org/W4405907205","https://openalex.org/W4411054984"],"related_works":[],"abstract_inverted_index":{"Drug":[0],"repositioning":[1,150],"offers":[2],"a":[3,42,65,69],"cost-effective":[4],"alternative":[5],"to":[6,24,72],"traditional":[7],"drug":[8,50,118,149],"development":[9],"by":[10],"identifying":[11,90],"new":[12],"uses":[13],"for":[14,45],"existing":[15],"drugs.":[16],"Recent":[17],"advances":[18,142],"leverage":[19],"Graph":[20],"Neural":[21],"Networks":[22],"(GNNs)":[23],"model":[25,62],"complex":[26],"biological":[27,105],"data,":[28],"showing":[29],"promise":[30],"in":[31,89,148],"predicting":[32],"novel":[33],"drug-disease":[34,92],"associations;":[35],"however,":[36],"these":[37,137],"frameworks":[38],"often":[39],"lack":[40],"explainability,":[41],"critical":[43],"factor":[44],"validating":[46],"predictions":[47,163],"and":[48,75,126,129,168],"understanding":[49],"mechanisms.":[51],"Here,":[52],"we":[53],"introduce":[54],"Drug-Based":[55],"Reasoning":[56],"Explainer":[57],"(DBR-X),":[58],"an":[59],"explainable":[60],"GNN":[61],"that":[63,140,156],"integrates":[64],"link-prediction":[66,83],"module":[67,71],"with":[68,115],"path-identification":[70],"generate":[73],"interpretable":[74],"faithful":[76],"explanations.":[77],"When":[78],"benchmarked":[79],"against":[80],"other":[81],"GNN-based":[82],"frameworks,":[84],"DBR-X":[85,104,141,170],"achieves":[86],"superior":[87],"performance":[88],"known":[91],"associations,":[93],"demonstrating":[94],"higher":[95],"accuracy":[96],"across":[97],"all":[98],"evaluation":[99],"metrics.":[100],"The":[101],"quality":[102],"of":[103,121,131,145,161],"explanations":[106,155],"was":[107],"evaluated":[108],"through":[109],"multiple":[110],"complementary":[111],"approaches,":[112],"including":[113],"comparison":[114],"manually":[116],"curated":[117],"mechanisms,":[119],"assessment":[120],"explanation":[122],"faithfulness":[123],"using":[124],"deletion":[125],"insertion":[127],"studies,":[128],"measurement":[130],"stability":[132],"under":[133],"graph":[134],"perturbations.":[135],"Together,":[136],"results":[138],"show":[139],"the":[143,146,159],"state":[144],"art":[147],"while":[151],"providing":[152],"multi-hop":[153],"mechanistic":[154],"can":[157],"facilitate":[158],"translation":[160],"computational":[162],"into":[164],"clinical":[165],"applications.":[166],"Availability":[167],"implementation:":[169],"package":[171],"is":[172],"freely":[173],"accessible":[174],"from":[175],"online":[176],"repository":[177],"https://github.com/SuLab/DBR-X.":[178]},"counts_by_year":[],"updated_date":"2026-04-09T08:11:56.329763","created_date":"2026-01-15T00:00:00"}
