{"id":"https://openalex.org/W4387114475","doi":"https://doi.org/10.1021/acs.jcim.3c00824","title":"<i>De Novo</i> Generation of Chemical Structures of Inhibitor and Activator Candidates for Therapeutic Target Proteins by a Transformer-Based Variational Autoencoder and Bayesian Optimization","display_name":"<i>De Novo</i> Generation of Chemical Structures of Inhibitor and Activator Candidates for Therapeutic Target Proteins by a Transformer-Based Variational Autoencoder and Bayesian Optimization","publication_year":2023,"publication_date":"2023-09-28","ids":{"openalex":"https://openalex.org/W4387114475","doi":"https://doi.org/10.1021/acs.jcim.3c00824","pmid":"https://pubmed.ncbi.nlm.nih.gov/37768595"},"language":"en","primary_location":{"id":"doi:10.1021/acs.jcim.3c00824","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.3c00824","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5092956928","display_name":"Yuki Matsukiyo","orcid":"https://orcid.org/0000-0003-0699-9970"},"institutions":[{"id":"https://openalex.org/I207014233","display_name":"Kyushu Institute of Technology","ror":"https://ror.org/02278tr80","country_code":"JP","type":"education","lineage":["https://openalex.org/I207014233"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Yuki Matsukiyo","raw_affiliation_strings":["Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, Fukuoka 820-8502, Japan"],"affiliations":[{"raw_affiliation_string":"Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, Fukuoka 820-8502, Japan","institution_ids":["https://openalex.org/I207014233"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5055333285","display_name":"Chikashige Yamanaka","orcid":"https://orcid.org/0000-0001-8302-9316"},"institutions":[{"id":"https://openalex.org/I207014233","display_name":"Kyushu Institute of Technology","ror":"https://ror.org/02278tr80","country_code":"JP","type":"education","lineage":["https://openalex.org/I207014233"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Chikashige Yamanaka","raw_affiliation_strings":["Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, Fukuoka 820-8502, Japan"],"affiliations":[{"raw_affiliation_string":"Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, Fukuoka 820-8502, Japan","institution_ids":["https://openalex.org/I207014233"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5035394108","display_name":"Yoshihiro Yamanishi","orcid":"https://orcid.org/0000-0003-2279-8773"},"institutions":[{"id":"https://openalex.org/I207014233","display_name":"Kyushu Institute of Technology","ror":"https://ror.org/02278tr80","country_code":"JP","type":"education","lineage":["https://openalex.org/I207014233"]},{"id":"https://openalex.org/I60134161","display_name":"Nagoya University","ror":"https://ror.org/04chrp450","country_code":"JP","type":"education","lineage":["https://openalex.org/I60134161"]}],"countries":["JP"],"is_corresponding":true,"raw_author_name":"Yoshihiro Yamanishi","raw_affiliation_strings":["Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, Fukuoka 820-8502, Japan","Graduate School of Informatics, Nagoya University, Chikusa, Nagoya, Aichi 464-8601, Japan"],"affiliations":[{"raw_affiliation_string":"Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, Fukuoka 820-8502, Japan","institution_ids":["https://openalex.org/I207014233"]},{"raw_affiliation_string":"Graduate School of Informatics, Nagoya University, Chikusa, Nagoya, Aichi 464-8601, Japan","institution_ids":["https://openalex.org/I60134161"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5035394108"],"corresponding_institution_ids":["https://openalex.org/I207014233","https://openalex.org/I60134161"],"apc_list":null,"apc_paid":null,"fwci":2.4105,"has_fulltext":false,"cited_by_count":12,"citation_normalized_percentile":{"value":0.9079688,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":97,"max":100},"biblio":{"volume":"64","issue":"7","first_page":"2345","last_page":"2355"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.9995999932289124,"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":0.9995999932289124,"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/T11663","display_name":"Viral Infectious Diseases and Gene Expression in Insects","score":0.9937000274658203,"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/T12576","display_name":"vaccines and immunoinformatics approaches","score":0.9869999885559082,"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/computer-science","display_name":"Computer science","score":0.6495399475097656},{"id":"https://openalex.org/keywords/inference","display_name":"Inference","score":0.5739524364471436},{"id":"https://openalex.org/keywords/bayesian-optimization","display_name":"Bayesian optimization","score":0.567071259021759},{"id":"https://openalex.org/keywords/autoencoder","display_name":"Autoencoder","score":0.5651513338088989},{"id":"https://openalex.org/keywords/drug-discovery","display_name":"Drug discovery","score":0.5298868417739868},{"id":"https://openalex.org/keywords/chemical-space","display_name":"Chemical space","score":0.5021374225616455},{"id":"https://openalex.org/keywords/transformer","display_name":"Transformer","score":0.4881304204463959},{"id":"https://openalex.org/keywords/computational-biology","display_name":"Computational biology","score":0.4875919222831726},{"id":"https://openalex.org/keywords/bayesian-probability","display_name":"Bayesian probability","score":0.47484710812568665},{"id":"https://openalex.org/keywords/bayesian-inference","display_name":"Bayesian inference","score":0.4707278311252594},{"id":"https://openalex.org/keywords/artificial-intelligence","display_name":"Artificial intelligence","score":0.4371006488800049},{"id":"https://openalex.org/keywords/bioinformatics","display_name":"Bioinformatics","score":0.2303396761417389},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.15371793508529663},{"id":"https://openalex.org/keywords/deep-learning","display_name":"Deep learning","score":0.14380139112472534},{"id":"https://openalex.org/keywords/engineering","display_name":"Engineering","score":0.1243145763874054}],"concepts":[{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.6495399475097656},{"id":"https://openalex.org/C2776214188","wikidata":"https://www.wikidata.org/wiki/Q408386","display_name":"Inference","level":2,"score":0.5739524364471436},{"id":"https://openalex.org/C2778049539","wikidata":"https://www.wikidata.org/wiki/Q17002908","display_name":"Bayesian optimization","level":2,"score":0.567071259021759},{"id":"https://openalex.org/C101738243","wikidata":"https://www.wikidata.org/wiki/Q786435","display_name":"Autoencoder","level":3,"score":0.5651513338088989},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.5298868417739868},{"id":"https://openalex.org/C99726746","wikidata":"https://www.wikidata.org/wiki/Q906396","display_name":"Chemical space","level":3,"score":0.5021374225616455},{"id":"https://openalex.org/C66322947","wikidata":"https://www.wikidata.org/wiki/Q11658","display_name":"Transformer","level":3,"score":0.4881304204463959},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.4875919222831726},{"id":"https://openalex.org/C107673813","wikidata":"https://www.wikidata.org/wiki/Q812534","display_name":"Bayesian probability","level":2,"score":0.47484710812568665},{"id":"https://openalex.org/C160234255","wikidata":"https://www.wikidata.org/wiki/Q812535","display_name":"Bayesian inference","level":3,"score":0.4707278311252594},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.4371006488800049},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.2303396761417389},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.15371793508529663},{"id":"https://openalex.org/C108583219","wikidata":"https://www.wikidata.org/wiki/Q197536","display_name":"Deep learning","level":2,"score":0.14380139112472534},{"id":"https://openalex.org/C127413603","wikidata":"https://www.wikidata.org/wiki/Q11023","display_name":"Engineering","level":0,"score":0.1243145763874054},{"id":"https://openalex.org/C165801399","wikidata":"https://www.wikidata.org/wiki/Q25428","display_name":"Voltage","level":2,"score":0.0},{"id":"https://openalex.org/C119599485","wikidata":"https://www.wikidata.org/wiki/Q43035","display_name":"Electrical engineering","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D001499","descriptor_name":"Bayes Theorem","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001499","descriptor_name":"Bayes Theorem","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001499","descriptor_name":"Bayes Theorem","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001499","descriptor_name":"Bayes Theorem","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D015195","descriptor_name":"Drug Design","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D015203","descriptor_name":"Reproducibility of Results","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015203","descriptor_name":"Reproducibility of Results","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015203","descriptor_name":"Reproducibility of Results","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015203","descriptor_name":"Reproducibility of Results","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020869","descriptor_name":"Gene Expression Profiling","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020869","descriptor_name":"Gene Expression Profiling","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020869","descriptor_name":"Gene Expression Profiling","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020869","descriptor_name":"Gene Expression Profiling","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D055808","descriptor_name":"Drug Discovery","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D055808","descriptor_name":"Drug Discovery","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D055808","descriptor_name":"Drug Discovery","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D055808","descriptor_name":"Drug Discovery","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true}],"locations_count":2,"locations":[{"id":"doi:10.1021/acs.jcim.3c00824","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.jcim.3c00824","pdf_url":null,"source":{"id":"https://openalex.org/S167262187","display_name":"Journal of Chemical Information and Modeling","issn_l":"1549-9596","issn":["1549-9596","1549-960X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Chemical Information and Modeling","raw_type":"journal-article"},{"id":"pmid:37768595","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/37768595","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":"Journal of chemical information and modeling","raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.6600000262260437,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"awards":[{"id":"https://openalex.org/G3516496435","display_name":null,"funder_award_id":"20H05797","funder_id":"https://openalex.org/F4320334764","funder_display_name":"Japan Society for the Promotion of Science"},{"id":"https://openalex.org/G5680769591","display_name":null,"funder_award_id":"JP22nk0101111","funder_id":"https://openalex.org/F4320311405","funder_display_name":"Japan Agency for Medical Research and Development"},{"id":"https://openalex.org/G789622214","display_name":null,"funder_award_id":"21H04915","funder_id":"https://openalex.org/F4320334764","funder_display_name":"Japan Society for the Promotion of Science"}],"funders":[{"id":"https://openalex.org/F4320311405","display_name":"Japan Agency for Medical Research and Development","ror":"https://ror.org/004rtk039"},{"id":"https://openalex.org/F4320334764","display_name":"Japan Society for the Promotion of Science","ror":"https://ror.org/00hhkn466"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":41,"referenced_works":["https://openalex.org/W1583837637","https://openalex.org/W1968753037","https://openalex.org/W1971375063","https://openalex.org/W1975147762","https://openalex.org/W1981276685","https://openalex.org/W1991462891","https://openalex.org/W2017254234","https://openalex.org/W2027482274","https://openalex.org/W2034549041","https://openalex.org/W2046219070","https://openalex.org/W2046588282","https://openalex.org/W2065812641","https://openalex.org/W2077004593","https://openalex.org/W2098967508","https://openalex.org/W2160592148","https://openalex.org/W2273267066","https://openalex.org/W2529996553","https://openalex.org/W2560677837","https://openalex.org/W2593632281","https://openalex.org/W2618625858","https://openalex.org/W2736137960","https://openalex.org/W2782083554","https://openalex.org/W2896822135","https://openalex.org/W2901476322","https://openalex.org/W2901775822","https://openalex.org/W2970107612","https://openalex.org/W2971080679","https://openalex.org/W2996962969","https://openalex.org/W2997782431","https://openalex.org/W2998571806","https://openalex.org/W2999977264","https://openalex.org/W3004974539","https://openalex.org/W3043969542","https://openalex.org/W3090915092","https://openalex.org/W3144501467","https://openalex.org/W3160789623","https://openalex.org/W3201411589","https://openalex.org/W4226048434","https://openalex.org/W4285603040","https://openalex.org/W4289761856","https://openalex.org/W4297951436"],"related_works":["https://openalex.org/W2973074952","https://openalex.org/W4283395020","https://openalex.org/W4320732452","https://openalex.org/W135095951","https://openalex.org/W4286980196","https://openalex.org/W4385588199","https://openalex.org/W3199987505","https://openalex.org/W4385760073","https://openalex.org/W2600435468","https://openalex.org/W2324927567"],"abstract_inverted_index":{"Deep":[0],"generative":[1],"models":[2],"for":[3,73,141,174],"molecular":[4],"generation":[5,52],"have":[6,33],"been":[7,35],"gaining":[8],"much":[9],"attention":[10],"as":[11],"structure":[12],"generators":[13],"to":[14,63,157,169],"accelerate":[15],"drug":[16],"discovery.":[17],"However,":[18],"most":[19],"previously":[20],"developed":[21],"methods":[22],"are":[23,101],"chemistry-centric":[24],"approaches,":[25],"and":[26,51,80,166],"comprehensive":[27],"biological":[28],"responses":[29],"in":[30,103,132],"the":[31,59,86,88,98,104,112,126,129],"cell":[32],"not":[34],"taken":[36],"into":[37],"account.":[38],"In":[39,85],"this":[40,152],"study,":[41],"we":[42],"propose":[43],"a":[44,116,171],"novel":[45],"computational":[46],"method,":[47],"TRIOMPHE-BOA":[48],"(transcriptome-based":[49],"inference":[50],"of":[53,68,90,106,115,128,134,138],"molecules":[54,92],"with":[55,148],"desired":[56],"phenotypes":[57],"using":[58,120],"Bayesian":[60,121],"optimization":[61],"algorithm),":[62],"generate":[64],"new":[65,107],"chemical":[66,108],"structures":[67,109,162],"inhibitor":[69],"or":[70,163],"activator":[71],"candidates":[72],"therapeutic":[74,143],"target":[75,144],"proteins":[76,145,158],"by":[77,110],"integrating":[78],"chemically":[79],"genetically":[81],"perturbed":[82],"transcriptome":[83,99],"profiles.":[84],"algorithm,":[87],"substructures":[89],"multiple":[91],"that":[93],"were":[94],"selected":[95],"based":[96],"on":[97],"analysis":[100],"fused":[102],"design":[105],"exploring":[111],"latent":[113],"space":[114],"Transformer-based":[117],"variational":[118],"autoencoder":[119],"optimization.":[122],"Our":[123],"results":[124],"demonstrate":[125],"usefulness":[127],"proposed":[130],"method":[131,153],"terms":[133],"having":[135],"high":[136],"reproducibility":[137],"existing":[139],"ligands":[140,165],"10":[142],"when":[146],"compared":[147],"previous":[149],"methods.":[150],"Moreover,":[151],"can":[154],"be":[155],"applied":[156],"without":[159],"detailed":[160],"3D":[161],"known":[164],"is":[167],"expected":[168],"become":[170],"powerful":[172],"tool":[173],"more":[175],"efficient":[176],"hit":[177],"identification.":[178]},"counts_by_year":[{"year":2026,"cited_by_count":2},{"year":2025,"cited_by_count":6},{"year":2024,"cited_by_count":4}],"updated_date":"2026-03-02T08:37:19.008085","created_date":"2025-10-10T00:00:00"}
