{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T22:13:13Z","timestamp":1778969593167,"version":"3.51.4"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"16","license":[{"start":{"date-parts":[[2018,3,24]],"date-time":"2018-03-24T00:00:00Z","timestamp":1521849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Annotation of genomic variants is an increasingly important and complex part of the analysis of sequence-based genomic analyses. Computational predictions of variant function are routinely incorporated into gene-based analyses of rare-variants, though to date most studies use limited information for assessing variant function that is often agnostic of the disease being studied.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In this work, we outline an annotation process motivated by the Alzheimer\u2019s Disease Sequencing Project, illustrate the impact of including tissue-specific transcript sets and sources of gene regulatory information and assess the potential impact of changing genomic builds on the annotation process. While these factors only impact a small proportion of total variant annotations (\u223c5%), they influence the potential analysis of a large fraction of genes (\u223c25%).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>Individual variant annotations are available via the NIAGADS GenomicsDB, at https:\/\/www.niagads.org\/genomics\/ tools-and-software\/databases\/genomics-database. Annotations are also available for bulk download at https:\/\/www.niagads.org\/datasets. Annotation processing software is available at http:\/\/www.icompbio.net\/resources\/software-and-downloads\/.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/bty177","type":"journal-article","created":{"date-parts":[[2018,3,23]],"date-time":"2018-03-23T20:50:40Z","timestamp":1521838240000},"page":"2724-2731","source":"Crossref","is-referenced-by-count":31,"title":["Functional annotation of genomic variants in studies of late-onset Alzheimer\u2019s disease"],"prefix":"10.1093","volume":"34","author":[{"given":"Mariusz","family":"Butkiewicz","sequence":"first","affiliation":[{"name":"Department of Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth E","family":"Blue","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, University of Washington, Seattle, WA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuk Yee","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueqiu","family":"Jian","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas Health Science Center, Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edoardo","family":"Marcora","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan E","family":"Renton","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Kuzma","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-San","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel C","family":"Koboldt","sequence":"additional","affiliation":[{"name":"Nationwide Children\u2019s Hospital, Columbus, OH, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan L","family":"Haines","sequence":"additional","affiliation":[{"name":"Department of Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9729-6519","authenticated-orcid":false,"given":"William S","family":"Bush","sequence":"additional","affiliation":[{"name":"Department of Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,3,24]]},"reference":[{"key":"2023012713002182900_bty177-B1","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nature11632","article-title":"An integrated map of genetic variation from 1,092 human genomes","volume":"491","author":"Abecasis","year":"2012","journal-title":"Nature"},{"key":"2023012713002182900_bty177-B2","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat. 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