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Genetic variations in\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    are responsible for interindividual heterogeneity in drug response that can lead to drug toxicity and ineffective treatment, making\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    one of the most important pharmacogenes. Prediction of CYP2D6 phenotype relies on curation of literature-derived functional studies to assign a functional status to\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    haplotypes. As the number of large-scale sequencing efforts grows, new haplotypes continue to be discovered, and assignment of function is challenging to maintain. To address this challenge, we have trained a convolutional neural network to predict functional status of\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    haplotypes, called Hubble.2D6. Hubble.2D6 predicts haplotype function from sequence data and was trained using two pre-training steps with a combination of real and simulated data. We find that Hubble.2D6 predicts\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    haplotype functional status with 88% accuracy in a held-out test set and explains 47.5% of the variance in\n                    <jats:italic>in vitro<\/jats:italic>\n                    functional data among star alleles with unknown function. Hubble.2D6 may be a useful tool for assigning function to haplotypes with uncurated function, and used for screening individuals who are at risk of being poor metabolizers.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1008399","type":"journal-article","created":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T13:44:20Z","timestamp":1604324660000},"page":"e1008399","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":44,"title":["Transfer learning enables prediction of CYP2D6 haplotype function"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8033-2499","authenticated-orcid":true,"given":"Gregory","family":"McInnes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8902-1155","authenticated-orcid":true,"given":"Rachel","family":"Dalton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7880-5843","authenticated-orcid":true,"given":"Katrin","family":"Sangkuhl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Whirl-Carrillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9869-1070","authenticated-orcid":true,"given":"Seung-been","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7274-9318","authenticated-orcid":true,"given":"Philip S.","family":"Tsao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6968-1893","authenticated-orcid":true,"given":"Andrea","family":"Gaedigk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3859-2905","authenticated-orcid":true,"given":"Russ B.","family":"Altman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0413-4140","authenticated-orcid":true,"given":"Erica L.","family":"Woodahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,11,2]]},"reference":[{"key":"pcbi.1008399.ref001","doi-asserted-by":"crossref","first-page":"689","DOI":"10.2165\/11318030-000000000-00000","article-title":"Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I","volume":"48","author":"S-F Zhou","year":"2009","journal-title":"Clin Pharmacokinet"},{"key":"pcbi.1008399.ref002","doi-asserted-by":"crossref","first-page":"761","DOI":"10.2165\/11318070-000000000-00000","article-title":"Polymorphism of human cytochrome P450 2D6 and its clinical significance: part II","volume":"48","author":"S-F Zhou","year":"2009","journal-title":"Clin Pharmacokinet"},{"key":"pcbi.1008399.ref003","article-title":"Physicochemical Properties, Biotransformation, and Transport Pathways of Established and Newly Approved Medications: A Systematic Review of the Top 200 Most Prescribed Drugs vs. the FDA-Approved Drugs Between 2005 and 2016","author":"A Saravanakumar","year":"2019","journal-title":"Clin Pharmacokinet."},{"key":"pcbi.1008399.ref004","doi-asserted-by":"crossref","first-page":"534","DOI":"10.3109\/09540261.2013.825581","article-title":"Complexities of CYP2D6 gene analysis and interpretation","volume":"25","author":"A. 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