{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T20:00:19Z","timestamp":1779134419122,"version":"3.51.4"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T00:00:00Z","timestamp":1706227200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["18K19930"],"award-info":[{"award-number":["18K19930"]}]},{"name":"JSPS KAKENHI","award":["20H05797"],"award-info":[{"award-number":["20H05797"]}]},{"name":"JSPS KAKENHI","award":["21K18327"],"award-info":[{"award-number":["21K18327"]}]},{"DOI":"10.13039\/501100004399","name":"Okawa Foundation for Information and Telecommunications","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Direct reprogramming (DR) is a process that directly converts somatic cells to target cells. Although DR via small molecules is safer than using transcription factors (TFs) in terms of avoidance of tumorigenic risk, the determination of DR-inducing small molecules is challenging.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Here we present a novel in silico method, DIRECTEUR, to predict small molecules that replace TFs for DR. We extracted DR-characteristic genes using transcriptome profiles of cells in which DR was induced by TFs, and performed a variant of simulated annealing to explore small molecule combinations with similar gene expression patterns with DR-inducing TFs. We applied DIRECTEUR to predicting combinations of small molecules that convert fibroblasts into neurons or cardiomyocytes, and were able to reproduce experimentally verified and functionally related molecules inducing the corresponding conversions. The proposed method is expected to be useful for practical applications in regenerative medicine.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>The code and data are available at the following link: https:\/\/github.com\/HamanoLaboratory\/DIRECTEUR.git.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btae048","type":"journal-article","created":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T06:45:45Z","timestamp":1706251545000},"source":"Crossref","is-referenced-by-count":1,"title":["DIRECTEUR: transcriptome-based prediction of small molecules that replace transcription factors for direct cell conversion"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8752-7053","authenticated-orcid":false,"given":"Momoko","family":"Hamano","sequence":"first","affiliation":[{"name":"Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology , Iizuka, Fukuoka 820-8502, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toru","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology , Iizuka, Fukuoka 820-8502, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryoku","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology , Iizuka, Fukuoka 820-8502, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology , Iizuka, Fukuoka 820-8502, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michio","family":"Iwata","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology , Iizuka, Fukuoka 820-8502, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun-ichi","family":"Takeshita","sequence":"additional","affiliation":[{"name":"Research Institute of Science for Safety and Sustainability, National Institute of Advanced Industrial Science and Technology (AIST) , Tsukuba, Ibaraki 305-8569, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7387-7562","authenticated-orcid":false,"given":"Ryohei","family":"Eguchi","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology , 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