{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:00:21Z","timestamp":1787497221557,"version":"build-2736575974"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","license":[{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The phosphatidylcholine floppase multidrug resistance protein 3 (MDR3) is an essential hepatobiliary transport protein. MDR3 dysfunction is associated with various liver diseases, ranging from severe progressive familial intrahepatic cholestasis to transient forms of intrahepatic cholestasis of pregnancy and familial gallstone disease. Single amino acid substitutions are often found as causative of dysfunction, but identifying the substitution effect in\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    studies is time and cost intensive. We developed variant assessor of MDR3 (Vasor), a machine learning\u2010based model to classify novel MDR3 missense variants into the categories benign or pathogenic. Vasor was trained on the largest data set to date that is specific for benign and pathogenic variants of MDR3 and uses general predictors, namely Evolutionary Models of Variant Effects (EVE), EVmutation, PolyPhen\u20102, I\u2010Mutant2.0, MUpro, MAESTRO, and PON\u2010P2 along with other variant properties, such as half\u2010sphere exposure and posttranslational modification site, as input. Vasor consistently outperformed the integrated general predictors and the external prediction tool MutPred2, leading to the current best prediction performance for MDR3 single\u2010site missense variants (on an external test set: F1\u2010score, 0.90; Matthew's correlation coefficient, 0.80). Furthermore, Vasor predictions cover the entire sequence space of MDR3. Vasor is accessible as a webserver at https:\/\/cpclab.uni\u2010duesseldorf.de\/mdr3_predictor\/ for users to rapidly obtain prediction results and a visualization of the substitution site within the MDR3 structure. The MDR3\u2010specific prediction tool Vasor can provide reliable predictions of single\u2010site amino acid substitutions, giving users a fast way to initially assess whether a variant is benign or pathogenic.\n                  <\/jats:p>","DOI":"10.1002\/hep4.2088","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T06:09:15Z","timestamp":1663308555000},"page":"3098-3111","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":8,"title":["Vasor: Accurate prediction of variant effects for amino acid substitutions in multidrug resistance protein 3"],"prefix":"10.1097","volume":"6","author":[{"given":"Annika","family":"Behrendt","sequence":"first","affiliation":[{"name":"Institute for Pharmaceutical and Medicinal Chemistry,Heinrich Heine University D\u00fcsseldorf,D\u00fcsseldorf,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pegah","family":"Golchin","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering and Information Technology,Technische Universit\u00e4t Darmstadt,Darmstadt,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"K\u00f6nig","sequence":"additional","affiliation":[{"name":"Institute for Pharmaceutical and Medicinal Chemistry,Heinrich Heine University D\u00fcsseldorf,D\u00fcsseldorf,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Mulnaes","sequence":"additional","affiliation":[{"name":"Institute for Pharmaceutical and Medicinal Chemistry,Heinrich Heine University D\u00fcsseldorf,D\u00fcsseldorf,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelie","family":"Stalke","sequence":"additional","affiliation":[{"name":"Department of Human Genetics,Hannover Medical School,Hannover,Germany"},{"name":"Division of Kidney, Department of Pediatric Gastroenterology and Hepatology, Liver, and Metabolic Diseases,Hannover Medical School,Hannover,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carola","family":"Dr\u00f6ge","sequence":"additional","affiliation":[{"name":"Department for Gastroenterology, Hepatology, and Infectious Diseases, Medical Faculty,Otto von Guericke University,Magdeburg,Germany"},{"name":"Department for Gastroenterology, Hepatology, and Infectious Diseases,University Hospital, Medical Faculty,Heinrich Heine University D\u00fcsseldorf,D\u00fcsseldorf,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Keitel","sequence":"additional","affiliation":[{"name":"Department for Gastroenterology, Hepatology, and Infectious Diseases, Medical Faculty,Otto von Guericke University,Magdeburg,Germany"},{"name":"Department for Gastroenterology, Hepatology, and Infectious Diseases,University Hospital, Medical Faculty,Heinrich Heine University D\u00fcsseldorf,D\u00fcsseldorf,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8613-1447","authenticated-orcid":false,"given":"Holger","family":"Gohlke","sequence":"additional","affiliation":[{"name":"Institute for Pharmaceutical and Medicinal Chemistry,Heinrich Heine University D\u00fcsseldorf,D\u00fcsseldorf,Germany"},{"name":"John\u2010von\u2010Neumann\u2010Institute for Computing, J\u00fclich Supercomputing Center, Institute of Biological Information Processing (IBI\u20107: Structural Biochemistry), and Institute of Bio\u2010 and Geosciences (IBG\u20104: Bioinformatics),Forschungszentrum J\u00fclich 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