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However, to screen and design selective JAK inhibitors is a daunting task due to the extremely high homology among four JAK isoforms. In this study, we aimed to simultaneously predict pIC<jats:sub>50<\/jats:sub> values of compounds for all JAK subtypes by constructing an interpretable GNN multitask regression model. The final model performance was positive, with R<jats:sup>2<\/jats:sup> values of 0.96, 0.79 and 0.78 on the training, validation and test sets, respectively. Meanwhile, we calculated and visualized atom weights, followed by the rank sum tests and local mean comparisons to obtain key atoms and substructures that could be fine-tuned to design selective JAK inhibitors. Several successful case studies have demonstrated that our approach is feasible and our model could learn the interactions between proteins and small molecules well, which could provide practitioners with a novel way to discover and design JAK inhibitors with selectivity.<\/jats:p>\n                <jats:p><jats:bold>Graphical Abstract<\/jats:bold><\/jats:p>","DOI":"10.1186\/s13321-022-00593-9","type":"journal-article","created":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T12:03:55Z","timestamp":1647345835000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["A multitask GNN-based interpretable model for discovery of selective JAK inhibitors"],"prefix":"10.1186","volume":"14","author":[{"given":"Yimeng","family":"Wang","sequence":"first","affiliation":[]},{"given":"Yaxin","family":"Gu","sequence":"additional","affiliation":[]},{"given":"Chaofeng","family":"Lou","sequence":"additional","affiliation":[]},{"given":"Yuning","family":"Gong","sequence":"additional","affiliation":[]},{"given":"Zengrui","family":"Wu","sequence":"additional","affiliation":[]},{"given":"Weihua","family":"Li","sequence":"additional","affiliation":[]},{"given":"Yun","family":"Tang","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9648-844X","authenticated-orcid":false,"given":"Guixia","family":"Liu","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2022,3,15]]},"reference":[{"issue":"Supplement_2","key":"593_CR1","doi-asserted-by":"publisher","first-page":"ii3","DOI":"10.1093\/rheumatology\/keab024","volume":"60","author":"FR Spinelli","year":"2021","unstructured":"Spinelli FR, Colbert RA, Gadina M (2021) JAK1: number one in the family; number one in inflammation. 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