{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T10:36:55Z","timestamp":1788345415722,"version":"build-2803163510"},"reference-count":25,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["OMICS: A Journal of Integrative Biology"],"published-print":{"date-parts":[[2022,6,1]]},"abstract":"<jats:p>\n                    Drug repurposing has broad importance in planetary health for therapeutics innovation in infectious diseases as well as common or rare chronic human diseases. Drug repurposing has also proved important to develop interventions against the COVID-19 pandemic. We propose a new approach for drug repurposing involving two-stage prediction and machine learning. First, diseases are clustered by gene expression on the premise that similar patterns of altered gene expression imply critical pathways shared in different disease conditions. Next, drug efficacy is assessed by the reversibility of abnormal gene expression, and results are clustered to identify repurposing targets. To cluster similar diseases, gene expression data from 262 cases of 31 diseases and 268 controls were analyzed by Uniform Manifold Approximation and Projection for Dimension Reduction followed by\n                    <jats:italic toggle=\"yes\">k<\/jats:italic>\n                    -means to optimize the number of clusters. For evaluation, we examined disease-specific gene expression data for inclusion, body myositis, polymyositis, and dermatomyositis (DM), and used LINCS L1000 characteristic direction signatures search engine (L1000CDS\n                    <jats:sup>2<\/jats:sup>\n                    ) to obtain lists of small-molecule compounds that reversed the expression patterns of these specifically altered genes as candidates for drug repurposing. Finally, the functions of affected genes were analyzed by Gene Set Enrichment Analysis to examine consistency with expected drug efficacy. Consequently, we found disease-specific gene expression, and importantly, identified 22 drugs such as KM 00927, I-BET, alvocidib, and vorinostat as candidates for repurposing. These were previously noted to be effective against two of the three diseases, and have a high probability of being effective against the other. The two-stage prediction approach to drug repurposing presented here offers innovation to inform future drug discovery and clinical trials in a variety of human diseases.\n                  <\/jats:p>","DOI":"10.1089\/omi.2022.0026","type":"journal-article","created":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T10:44:00Z","timestamp":1654512240000},"page":"339-347","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":39,"title":["A New Approach to Drug Repurposing with Two-Stage Prediction, Machine Learning, and Unsupervised Clustering of Gene Expression"],"prefix":"10.1177","volume":"26","author":[{"given":"Yi","family":"Cong","sequence":"first","affiliation":[{"name":"Laboratory of Information Biology, Information Science and Technology, Hokkaido University, Sapporo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misaki","family":"Shintani","sequence":"additional","affiliation":[{"name":"Laboratory of Information Biology, Information Science and Technology, Hokkaido University, Sapporo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuga","family":"Imanari","sequence":"additional","affiliation":[{"name":"Laboratory of Information Biology, Information Science and Technology, Hokkaido University, Sapporo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Osada","sequence":"additional","affiliation":[{"name":"Laboratory of Information Biology, Information Science and Technology, Hokkaido University, Sapporo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5711-2527","authenticated-orcid":false,"given":"Toshinori","family":"Endo","sequence":"additional","affiliation":[{"name":"Laboratory of Information Biology, Information Science and Technology, Hokkaido University, Sapporo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,6,13]]},"reference":[{"key":"e_1_3_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms16022"},{"key":"e_1_3_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddtec.2017.04.001"},{"key":"e_1_3_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/npjsba.2016.15"},{"key":"e_1_3_6_5_1","doi-asserted-by":"publisher","DOI":"10.33549\/physiolres.934765"},{"key":"e_1_3_6_6_1","author":"Garvey C","year":"2018","unstructured":"Garvey C. (2018). Interview with colin garvey, rensselaer polytechnic institute. Artificial intelligence and systems medicine convergence. OMICS J Integr Biol 22. DOI: 10.1089\/omi.2017.0218.","journal-title":"OMICS J Integr Biol"},{"key":"e_1_3_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1521"},{"key":"e_1_3_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2021.104264"},{"key":"e_1_3_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2013.11.005"},{"key":"e_1_3_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jphp.13273"},{"key":"e_1_3_6_11_1","article-title":"Analytics Vidhya","author":"Khyati M","year":"2019","unstructured":"Khyati M. (2019). Analytics Vidhya. How to Determine the Optimal K for K-Means? Pune, Maharashtra, 2019. https:\/\/medium.com\/analytics-vidhya\/how-to-determine-the-optimal-k-for-k-means-708505d204eb. Accessed July17, 2019.","journal-title":"How to Determine the Optimal K for K-Means? Pune, Maharashtra"},{"key":"e_1_3_6_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12272-019-01176-3"},{"key":"e_1_3_6_13_1","doi-asserted-by":"crossref","unstructured":"McInnes L Healy J and Melville J. (2018). UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction. DOI: 10.48550\/arXiv.1802.03426.","DOI":"10.21105\/joss.00861"},{"key":"e_1_3_6_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1758-2946-5-30"},{"key":"e_1_3_6_15_1","unstructured":"Nishino I. Classification of Autoimmune Myositis. Neurodiem 2020. https:\/\/www.neurodiem.jp\/news\/classification-of-autoimmune-myositis-5VZWDib2pYfHBLISriomq8. 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