{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:00:30Z","timestamp":1787317230153,"version":"build-2736575974"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U54AG065187"],"award-info":[{"award-number":["U54AG065187"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>The Target Enablement to Accelerate Therapy Development for AD (TREAT\u2010AD) bioinformatics pipeline employs a rank\u2010and\u2010organize strategy. Disease\u2010associated genes drive enrichment of large AD\u2010linked endophenotypes. However, these biological areas were too large to promote hypothesis development or target identification. Here we delineate subdomains that map to, and enrich, specific biological processes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      To refine the biodomains into more focused areas, we built\n                      <jats:italic>\u03ba<\/jats:italic>\n                      networks out of the Gene Ontology terms in the biodomain and employ shared gene annotation between terms to determine edge weights.\n                      <jats:italic>\u03ba<\/jats:italic>\n                      \u2010value filtration enabled us to identify data\u2010driven subdomains, which we employed in an analysis of TREAT\u2010AD harmonized datasets.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>The subdomain enrichment highlights core areas of biological impairment within the biodomain space and facilitates a deeper interpretation of large\u2010scale multiomic datasets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>The subdomain mapping of AD\u2010risk\u2010associated processes may facilitate an open\u2010source, open\u2010science shareable resource for the comparison of large datasets for the formulation of future hypotheses and identification of therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71403","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T03:36:12Z","timestamp":1781148972000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Alzheimer's disease biological domain sub\u2010stratification enhances the precision of functional analyses"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3573-5229","authenticated-orcid":false,"given":"Gregory A.","family":"Cary","sequence":"first","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor Maine USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai Sruthi Amirtha","family":"Ganesh","sequence":"additional","affiliation":[{"name":"University of Kansas  Lawrence Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Heath","sequence":"additional","affiliation":[{"name":"Sage Bionetworks  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Leal","sequence":"additional","affiliation":[{"name":"Sage Bionetworks  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Kampmann","sequence":"additional","affiliation":[{"name":"University of California San Francisco  San 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