{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T03:37:41Z","timestamp":1770781061933,"version":"3.50.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,5,22]],"date-time":"2022-05-22T00:00:00Z","timestamp":1653177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31800765"],"award-info":[{"award-number":["31800765"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFC2002902"],"award-info":[{"award-number":["2020YFC2002902"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001245","name":"Jeffrey Modell Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004348","name":"Stockholm County Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004348","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Distinguishing pathogenic variants from non-pathogenic ones remains a major challenge in clinical genetic testing of primary immunodeficiency (PID) patients. Most of the existing mutation pathogenicity prediction tools treat all mutations as homogeneous entities, ignoring the differences in characteristics of different genes, and use the same model for genes in different diseases. In this study, we developed a single nucleotide variant (SNV) pathogenicity prediction tool, Variant Impact Predictor for PIDs (VIPPID; https:\/\/mylab.shinyapps.io\/VIPPID\/), which was tailored for PIDs genes and used a specific model for each of the most prevalent PID known genes. It employed a Conditional Inference Forest model and utilized information of 85 features of SNVs and scores from 20 existing prediction tools. Evaluation of VIPPID showed that it had superior performance (area under the curve\u2009=\u20090.91) over non-specific conventional tools. In addition, we also showed that the gene-specific model outperformed the non-gene-specific models. Our study demonstrated that disease-specific and gene-specific models can improve SNV pathogenicity prediction performance. This observation supports the notion that each feature of mutations in the model can be potentially used, in a new algorithm, to investigate the characteristics and function of the encoded proteins.<\/jats:p>","DOI":"10.1093\/bib\/bbac176","type":"journal-article","created":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T11:13:03Z","timestamp":1650453183000},"source":"Crossref","is-referenced-by-count":15,"title":["VIPPID: a gene-specific single nucleotide variant pathogenicity prediction tool for primary immunodeficiency diseases"],"prefix":"10.1093","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7185-6445","authenticated-orcid":false,"given":"Mingyan","family":"Fang","sequence":"first","affiliation":[{"name":"BGI-Shenzhen , Shenzhen 518083, China"},{"name":"Division of Clinical Immunology at the Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge , SE-141 86 Stockholm, Sweden"},{"name":"BGI-Singapore , Singapore 138567, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Su","sequence":"additional","affiliation":[{"name":"School of Biotechnology and Biomolecular Sciences, Faculty of Science, The University of New South Wales , Sydney, New South Wales, Australia"},{"name":"GenieUs Genomics, 19A Boundary St, Darlinghurst NSW 2010 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hassan","family":"Abolhassani","sequence":"additional","affiliation":[{"name":"Division of Clinical Immunology at the Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge , SE-141 86 Stockholm, Sweden"},{"name":"Department of Biosciences and Nutrition, NEO, Karolinska Institutet , SE14183 Huddinge, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuval","family":"Itan","sequence":"additional","affiliation":[{"name":"The Charles Bronfman Institute for Personalized Medicine, Icahn School 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