{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T11:42:34Z","timestamp":1753875754167,"version":"3.41.2"},"reference-count":9,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"content-version":"vor","delay-in-days":20,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HG003747"],"award-info":[{"award-number":["HG003747"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>The ENCODE project generated a large collection of eCLIP-seq RNA binding protein (RBP) profiling data with accompanying RNA-seq transcriptomes of shRNA knockdown of RBPs. These data could have utility in understanding the functional impact of genetic variants, however their potential has not been fully exploited. We implement INCA (Integrative annotation scores of variants for impact on RBP activities) as a multi-step genetic variant scoring approach that leverages the ENCODE RBP data together with ClinVar and integrates multiple computational approaches to aggregate evidence.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>INCA evaluates variant impacts on RBP activities by leveraging genotypic differences in cell lines used for eCLIP-seq. We show that INCA provides critical specificity, beyond generic scoring for RBP binding disruption, for candidate variants and their linkage-disequilibrium partners. As a result, it can, on average, augment scoring of 46.2% of the candidate variants beyond generic scoring for RBP binding disruption and aid in variant prioritization for follow-up analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>INCA is implemented in R and is available at https:\/\/github.com\/keleslab\/INCA.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btae181","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T22:08:15Z","timestamp":1713478095000},"source":"Crossref","is-referenced-by-count":0,"title":["Integrative annotation scores of variants for impact on RNA binding protein activities"],"prefix":"10.1093","volume":"40","author":[{"given":"Jingqi","family":"Duan","sequence":"first","affiliation":[{"name":"Department of Statistics, University of Wisconsin , Madison, WI, 53706, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey P","family":"Gasch","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, University of Wiconsin , Madison, WI, 53706, United States"},{"name":"Center for Genomic Science Innovation, University of Wisconsin , Madison, WI, 53706, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9048-0922","authenticated-orcid":false,"given":"S\u00fcnd\u00fcz","family":"Kele\u015f","sequence":"additional","affiliation":[{"name":"Department of Statistics, University of Wisconsin , Madison, WI, 53706, United States"},{"name":"Center for Genomic Science Innovation, University of Wisconsin , Madison, WI, 53706, United States"},{"name":"Department of Biostatistics and Medical Informatics, University of Wisconsin , Madison, WI, 53706, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,4,18]]},"reference":[{"key":"2024042423461203200_btae181-B1","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/s41588-018-0081-4","article-title":"Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types","volume":"50","author":"Finucane","year":"2018","journal-title":"Nature Genetics"},{"key":"2024042423461203200_btae181-B2","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/s41586-021-04064-3","article-title":"The power of genetic diversity in genome-wide association studies of lipids","volume":"600","author":"Graham","year":"2021","journal-title":"Nature"},{"volume-title":"Intelligent Systems Design and Applications. ISDA 2021. Lecture Notes in Networks and Systems","year":"2022","author":"Hebbar","key":"2024042423461203200_btae181-B3"},{"key":"2024042423461203200_btae181-B4","doi-asserted-by":"crossref","first-page":"D882","DOI":"10.1093\/nar\/gkz1062","article-title":"New developments on the encyclopedia of DNA elements (encode) data portal","volume":"48","author":"Luo","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"2024042423461203200_btae181-B5","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/s41588-020-00761-3","article-title":"Genome-wide landscape of RNA-binding protein target site dysregulation reveals a major impact on psychiatric disorder risk","volume":"53","author":"Park","year":"2021","journal-title":"Nat Genet"},{"key":"2024042423461203200_btae181-B6","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1093\/bib\/bby039","article-title":"Regulatory variants: from detection to predicting impact","volume":"20","author":"Rojano","year":"2019","journal-title":"Brief Bioinform"},{"key":"2024042423461203200_btae181-B7","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s13059-020-01982-9","article-title":"Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins","volume":"21","author":"Van Nostrand","year":"2020","journal-title":"Genome Biol"},{"author":"Zanetti","key":"2024042423461203200_btae181-B8"},{"key":"2024042423461203200_btae181-B9","doi-asserted-by":"crossref","first-page":"3353","DOI":"10.1093\/bioinformatics\/btv328","article-title":"atSNP: transcription factor binding affinity testing for regulatory SNP detection","volume":"31","author":"Zuo","year":"2015","journal-title":"Bioinformatics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btae181\/57274194\/btae181.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/40\/4\/btae181\/57322337\/btae181.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/40\/4\/btae181\/57322337\/btae181.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T23:46:26Z","timestamp":1714002386000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btae181\/7651197"}},"subtitle":[],"editor":[{"given":"Peter","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,3,29]]},"references-count":9,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,3,29]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btae181","relation":{},"ISSN":["1367-4811"],"issn-type":[{"type":"electronic","value":"1367-4811"}],"subject":[],"published-other":{"date-parts":[[2024,4,1]]},"published":{"date-parts":[[2024,3,29]]},"article-number":"btae181"}}