{"id":"https://openalex.org/W4412379716","doi":"https://doi.org/10.3389/fphar.2025.1564339","title":"MD-Syn: synergistic drug combination prediction based on a multidimensional feature fusion method and attention mechanisms","display_name":"MD-Syn: synergistic drug combination prediction based on a multidimensional feature fusion method and attention mechanisms","publication_year":2025,"publication_date":"2025-07-14","ids":{"openalex":"https://openalex.org/W4412379716","doi":"https://doi.org/10.3389/fphar.2025.1564339","pmid":"https://pubmed.ncbi.nlm.nih.gov/40727094"},"language":"en","primary_location":{"id":"doi:10.3389/fphar.2025.1564339","doi":"https://doi.org/10.3389/fphar.2025.1564339","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fphar.2025.1564339","pdf_url":"https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1564339/pdf","source":{"id":"https://openalex.org/S132108250","display_name":"Frontiers in Pharmacology","issn_l":"1663-9812","issn":["1663-9812"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","ki-jl-1","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Pharmacology","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1564339/pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":null,"display_name":"XinXin Ge","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I25846049","display_name":"National Tsing Hua University","ror":"https://ror.org/00zdnkx70","country_code":"TW","type":"education","lineage":["https://openalex.org/I25846049"]}],"countries":["TW"],"is_corresponding":false,"raw_author_name":"XinXin Ge","raw_affiliation_strings":["School of Medicine, National Tsing Hua University, Hsinchu, Taiwan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"School of Medicine, National Tsing Hua University, Hsinchu, Taiwan","institution_ids":["https://openalex.org/I25846049"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5103108517","display_name":"Yi-Ting Lee","orcid":"https://orcid.org/0000-0001-5859-847X","observed_orcids":["https://orcid.org/0000-0001-5859-847X"]},"institutions":[{"id":"https://openalex.org/I25846049","display_name":"National Tsing Hua University","ror":"https://ror.org/00zdnkx70","country_code":"TW","type":"education","lineage":["https://openalex.org/I25846049"]}],"countries":["TW"],"is_corresponding":false,"raw_author_name":"Yi-Ting Lee","raw_affiliation_strings":["Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan","institution_ids":["https://openalex.org/I25846049"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5069813355","display_name":"Shan\u2010Ju Yeh","orcid":"https://orcid.org/0000-0001-7006-6396","observed_orcids":["https://orcid.org/0000-0001-7006-6396"]},"institutions":[{"id":"https://openalex.org/I25846049","display_name":"National Tsing Hua University","ror":"https://ror.org/00zdnkx70","country_code":"TW","type":"education","lineage":["https://openalex.org/I25846049"]}],"countries":["TW"],"is_corresponding":true,"raw_author_name":"Shan-Ju Yeh","raw_affiliation_strings":["Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan","Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan","School of Medicine, National Tsing Hua University, Hsinchu, Taiwan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan","institution_ids":["https://openalex.org/I25846049"]},{"raw_affiliation_string":"Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan","institution_ids":["https://openalex.org/I25846049"]},{"raw_affiliation_string":"School of Medicine, National Tsing Hua University, Hsinchu, Taiwan","institution_ids":["https://openalex.org/I25846049"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5069813355"],"corresponding_institution_ids":["https://openalex.org/I25846049"],"apc_list":{"value":3150,"currency":"CHF","value_usd":3801},"apc_paid":{"value":3150,"currency":"CHF","value_usd":3801},"fwci":4.307,"has_fulltext":true,"cited_by_count":9,"citation_normalized_percentile":{"value":0.95056497,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":96,"max":99},"biblio":{"volume":"16","issue":null,"first_page":"1564339","last_page":"1564339"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.9984999895095825,"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":0.9984999895095825,"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":9.999999747378752e-05,"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/T10885","display_name":"Gene expression and cancer classification","score":9.999999747378752e-05,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/drug-synergy","display_name":"drug synergy","score":0.9649999737739563},{"id":"https://openalex.org/keywords/multi-head-attention","display_name":"multi-head attention","score":0.9440000057220459},{"id":"https://openalex.org/keywords/drug-combination-screening","display_name":"drug combination screening","score":0.5320000052452087},{"id":"https://openalex.org/keywords/interpretability","display_name":"interpretability","score":0.8299999833106995},{"id":"https://openalex.org/keywords/web-portal","display_name":"web portal","score":0.6370000243186951}],"concepts":[{"id":"https://openalex.org/C2781067378","wikidata":"https://www.wikidata.org/wiki/Q17027399","display_name":"Interpretability","level":2,"score":0.7350636720657349},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.6489362120628357},{"id":"https://openalex.org/C2776401178","wikidata":"https://www.wikidata.org/wiki/Q12050496","display_name":"Feature (linguistics)","level":2,"score":0.6402906179428101},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.5890424251556396},{"id":"https://openalex.org/C119857082","wikidata":"https://www.wikidata.org/wiki/Q2539","display_name":"Machine learning","level":1,"score":0.5337812304496765},{"id":"https://openalex.org/C95623464","wikidata":"https://www.wikidata.org/wiki/Q1096149","display_name":"Classifier (UML)","level":2,"score":0.525924563407898},{"id":"https://openalex.org/C41608201","wikidata":"https://www.wikidata.org/wiki/Q980509","display_name":"Embedding","level":2,"score":0.46159836649894714},{"id":"https://openalex.org/C2989108626","wikidata":"https://www.wikidata.org/wiki/Q904407","display_name":"Drug target","level":2,"score":0.41504934430122375},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.14780327677726746},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.0},{"id":"https://openalex.org/C41895202","wikidata":"https://www.wikidata.org/wiki/Q8162","display_name":"Linguistics","level":1,"score":0.0},{"id":"https://openalex.org/C138885662","wikidata":"https://www.wikidata.org/wiki/Q5891","display_name":"Philosophy","level":0,"score":0.0}],"mesh":[],"locations_count":4,"locations":[{"id":"doi:10.3389/fphar.2025.1564339","doi":"https://doi.org/10.3389/fphar.2025.1564339","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fphar.2025.1564339","pdf_url":"https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1564339/pdf","source":{"id":"https://openalex.org/S132108250","display_name":"Frontiers in Pharmacology","issn_l":"1663-9812","issn":["1663-9812"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","ki-jl-1","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Pharmacology","raw_type":"journal-article"},{"id":"pmid:40727094","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/40727094","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,"listed_in":[],"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":"Frontiers in pharmacology","raw_type":"Journal Article"},{"id":"pmh:oai:pubmedcentral.nih.gov:12301336","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12301336","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"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":"Front Pharmacol","raw_type":"Text"},{"id":"pmh:oai:doaj.org/article:9cb8c27043554e878f755f1e159f48c4","doi":null,"is_oa":true,"landing_page_url":"https://doaj.org/article/9cb8c27043554e878f755f1e159f48c4","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-sa","license_id":"https://openalex.org/licenses/cc-by-sa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Frontiers in Pharmacology, Vol 16 (2025)","raw_type":"article"}],"best_oa_location":{"id":"doi:10.3389/fphar.2025.1564339","doi":"https://doi.org/10.3389/fphar.2025.1564339","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fphar.2025.1564339","pdf_url":"https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1564339/pdf","source":{"id":"https://openalex.org/S132108250","display_name":"Frontiers in Pharmacology","issn_l":"1663-9812","issn":["1663-9812"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","ki-jl-1","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Pharmacology","raw_type":"journal-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.8371999859809875}],"sustainable_development_goals_aurora":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.6899999976158142}],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320316499","display_name":"National Applied Research Laboratories","ror":"https://ror.org/05wcstg80"},{"id":"https://openalex.org/F4320331164","display_name":"National Science and Technology Council","ror":"https://ror.org/00wnb9798"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W4412379716.pdf","grobid_xml":"https://content.openalex.org/works/W4412379716.grobid-xml"},"referenced_works_count":57,"referenced_works":["https://openalex.org/W1578932543","https://openalex.org/W1614298861","https://openalex.org/W1696775091","https://openalex.org/W1984328540","https://openalex.org/W1988790447","https://openalex.org/W2003516462","https://openalex.org/W2015789827","https://openalex.org/W2059516061","https://openalex.org/W2103562758","https://openalex.org/W2104919487","https://openalex.org/W2114621192","https://openalex.org/W2126506845","https://openalex.org/W2150455229","https://openalex.org/W2295598076","https://openalex.org/W2299417213","https://openalex.org/W2344726805","https://openalex.org/W2366141641","https://openalex.org/W2606780347","https://openalex.org/W2612467560","https://openalex.org/W2626778328","https://openalex.org/W2766453196","https://openalex.org/W2775061087","https://openalex.org/W2786672974","https://openalex.org/W2793608852","https://openalex.org/W2911964244","https://openalex.org/W2917858269","https://openalex.org/W2922229918","https://openalex.org/W2944727022","https://openalex.org/W2949524414","https://openalex.org/W2950860419","https://openalex.org/W2952583555","https://openalex.org/W2968210605","https://openalex.org/W2982291409","https://openalex.org/W2982555156","https://openalex.org/W2989954637","https://openalex.org/W3040045990","https://openalex.org/W3086347240","https://openalex.org/W3127930610","https://openalex.org/W3172530361","https://openalex.org/W3184417398","https://openalex.org/W3193719766","https://openalex.org/W3203908308","https://openalex.org/W3205082786","https://openalex.org/W4206718607","https://openalex.org/W4288456908","https://openalex.org/W4289315841","https://openalex.org/W4311247426","https://openalex.org/W4313485929","https://openalex.org/W4327676467","https://openalex.org/W4384818885","https://openalex.org/W4385751491","https://openalex.org/W4387107820","https://openalex.org/W4389885905","https://openalex.org/W4401731151","https://openalex.org/W4404387002","https://openalex.org/W6707620307","https://openalex.org/W6910681941"],"related_works":["https://openalex.org/W2905433371","https://openalex.org/W2888392564","https://openalex.org/W4310278675","https://openalex.org/W4388422664","https://openalex.org/W4390569940","https://openalex.org/W4361193272","https://openalex.org/W2963326959","https://openalex.org/W4388685194","https://openalex.org/W4312407344","https://openalex.org/W2894289927"],"abstract_inverted_index":{"Drug":[0],"combination":[1,125,194,226],"therapies":[2],"have":[3,40,214],"shown":[4],"promising":[5],"therapeutic":[6],"efficacy":[7],"in":[8,34,140],"complex":[9,55],"diseases":[10],"and":[11,65,83,96,116,198],"demonstrated":[12],"the":[13,20,54,132,144,158,179],"potential":[14],"to":[15,30,43,51,190,210],"reduce":[16],"drug":[17,25,59,88,124,193,225],"resistance.":[18],"However,":[19],"vast":[21],"number":[22],"of":[23,103,138,181,224],"possible":[24],"combinations":[26],"makes":[27],"it":[28],"difficult":[29],"screen":[31],"them":[32],"all":[33],"traditional":[35],"experiments.":[36],"Although":[37],"computational":[38,74],"models":[39],"been":[41],"developed":[42,215],"address":[44],"this":[45,68,211],"challenge,":[46],"existing":[47],"methods":[48],"often":[49],"struggle":[50],"fully":[52],"capture":[53],"biological":[56],"interactions":[57],"underlying":[58],"synergy,":[60],"limiting":[61],"their":[62],"predictive":[63],"accuracy":[64],"generalization.":[66],"In":[67,156,183],"study,":[69],"we":[70,213],"proposed":[71],"MD-Syn,":[72],"a":[73,78,104,110,117,216],"framework":[75,189],"based":[76,229],"on":[77,173,230],"multidimensional":[79],"feature":[80,98,106,112,168,176],"fusion":[81],"method":[82],"multi-head":[84,159],"attention":[85,160],"mechanisms.":[86],"Given":[87],"pair-cell":[89],"line":[90,201],"triplets,":[91],"MD-Syn":[92,127,148,185],"considers":[93],"both":[94],"one-":[95],"two-dimensional":[97,111],"spaces":[99],"simultaneously.":[100],"It":[101],"consists":[102],"one-dimensional":[105],"embedding":[107,113],"module":[108,114],"(1D-FEM),":[109],"(2D-FEM),":[115],"deep":[118],"neural":[119],"network-based":[120],"classifier":[121],"for":[122],"synergistic":[123,192],"prediction.":[126],"achieved":[128],"an":[129,187],"area":[130],"under":[131],"receiver":[133],"operating":[134],"characteristic":[135],"curve":[136],"(AUROC)":[137],"0.919":[139],"five-fold":[141],"cross-validation,":[142],"outperforming":[143],"state-of-the-art":[145],"methods.":[146],"Furthermore,":[147],"showed":[149],"comparable":[150],"results":[151],"across":[152],"four":[153],"independent":[154],"datasets.":[155],"addition,":[157],"mechanisms":[161],"not":[162],"only":[163],"learn":[164],"embeddings":[165],"from":[166],"different":[167],"aspects":[169],"but":[170],"also":[171],"focus":[172],"essential":[174],"interactive":[175],"elements,":[177],"improving":[178],"interpretability":[180],"MD-Syn.":[182],"summary,":[184],"is":[186],"interpretable":[188],"prioritize":[191],"pairs":[195],"using":[196],"chemical":[197],"cancer":[199],"cell":[200],"gene":[202],"expression":[203],"profiles.":[204],"To":[205],"facilitate":[206],"broader":[207],"community":[208],"access":[209],"model,":[212],"web":[217],"portal":[218],"(https://labyeh104-2.life.nthu.edu.tw/)":[219],"that":[220],"enables":[221],"customized":[222],"predictions":[223],"synergy":[227],"effects":[228],"user-specified":[231],"compounds.":[232]},"counts_by_year":[{"year":2026,"cited_by_count":6},{"year":2025,"cited_by_count":3}],"updated_date":"2026-10-16T09:59:22.235173","created_date":"2025-10-10T00:00:00"}