{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T19:37:51Z","timestamp":1779219471091,"version":"3.51.4"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T00:00:00Z","timestamp":1724976000000},"content-version":"vor","delay-in-days":36,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Synthetic lethality (SL) has shown great promise for the discovery of novel targets in cancer. CRISPR double-knockout (CDKO) technologies can only screen several hundred genes and their combinations, but not genome-wide. Therefore, good SL prediction models are highly needed for genes and gene pairs selection in CDKO experiments. However, lack of scalable SL properties prevents generalizability of SL interactions to out-of-sample data, thereby hindering modeling efforts. In this paper, we recognize that SL connectivity is a scalable and generalizable SL property. We develop a novel two-step multilayer encoder for individual sample-specific SL prediction model (MLEC-iSL), which predicts SL connectivity first and SL interactions subsequently. MLEC-iSL has three encoders, namely, gene, graph, and transformer encoders. MLEC-iSL achieves high SL prediction performance in K562 (AUPR, 0.73; AUC, 0.72) and Jurkat (AUPR, 0.73; AUC, 0.71) cells, while no existing methods exceed 0.62 AUPR and AUC. The prediction performance of MLEC-iSL is validated in a CDKO experiment in 22Rv1 cells, yielding a 46.8% SL rate among 987 selected gene pairs. The screen also reveals SL dependency between apoptosis and mitosis cell death pathways.<\/jats:p>","DOI":"10.1093\/bib\/bbae425","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T03:20:42Z","timestamp":1724988042000},"source":"Crossref","is-referenced-by-count":12,"title":["Synthetic lethal connectivity and graph transformer improve synthetic lethality prediction"],"prefix":"10.1093","volume":"25","author":[{"given":"Kunjie","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Biomedical Informatics , College of Medicine, , 1800 Cannon Drive, Columbus, OH 43210, United States"},{"name":"The Ohio State University , College of Medicine, , 1800 Cannon Drive, Columbus, OH 43210, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9238-1650","authenticated-orcid":false,"given":"Birkan","family":"G\u00f6kba\u011f","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics , College of Medicine, , 1800 Cannon Drive, Columbus, OH 43210, United States"},{"name":"The Ohio State University , College of Medicine, , 1800 Cannon Drive, Columbus, OH 43210, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics , College of Pharmacy, , 500 W. 12 ave, Columbus, OH 43210, United States"},{"name":"The Ohio State University , College of Pharmacy, , 500 W. 12 ave, Columbus, OH 43210, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shangjia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics , College of Medicine, , 1800 Cannon Drive, Columbus, OH 43210, United States"},{"name":"The Ohio State University , College of Medicine, , 1800 Cannon Drive, Columbus, OH 43210, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yirui","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics , College of Pharmacy, , 500 W. 12 ave, Columbus, OH 43210, United States"},{"name":"The Ohio State University , College of Pharmacy, , 500 W. 12 ave, Columbus, OH 43210, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingling","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics , College of Medicine, , 1800 Cannon Drive, Columbus, OH 43210, United States"},{"name":"The Ohio State University , College of Medicine, , 1800 Cannon Drive, Columbus, OH 43210, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijun","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics , College of Medicine, , 1800 Cannon Drive, Columbus, OH 43210, United 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