{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:14:41Z","timestamp":1788437681397,"version":"build-2803163510"},"reference-count":74,"publisher":"Wiley","issue":"49","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1DK114356"],"award-info":[{"award-number":["RO1DK114356"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1HG006348"],"award-info":[{"award-number":["UM1HG006348"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Circadian rhythms are involved in nearly all physiological processes, and their disruption increases disease risk. Aligning drug administration timing with the body's internal clock, known as circadian medicine, holds promise for improving treatment efficacy and safety. However, systematic strategies to identify circadian\u2010regulated therapeutic targets remain limited. Here, we develop RHINO (RHythmic Interacting Network for multi\u2010Omics), an integrative multi\u2010omics framework for exploring circadian regulation across diverse genetic and disease contexts, and prioritizing druggable circadian targets. Applying RHINO reveals that human genetic variation broadly shapes rhythmic gene expression, with approximately 80% of FDA\u2010approved drug targets exhibiting genotype\u2010dependent rhythmicity, thereby substantially expanding the druggable target landscape for more precise circadian medicine. Circadian analyses across cancer types and diseases further identify genes that consistently lose rhythmic expression, highlighting conserved circadian vulnerabilities linked to disease progression. Integrative regulatory analyses nominate upstream transcriptional regulators, including Estrogen Receptor \u03b1, associated with rhythmic disruption. Although the circadian rhythm of estrogen signaling has been recognized for decades, we show that this rhythmicity exhibits time\u2010of\u2010day\u2013dependent metabolic responses in preclinical mouse models. Together, RHINO provides a community\u2010accessible multi\u2010omics platform that integrates genetic variation, disease\u2010associated circadian remodeling, and regulatory inference to advance circadian medicine (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/hanlaboratory.com\/RHINO\">https:\/\/hanlaboratory.com\/RHINO<\/jats:ext-link>\n                    ).\n                  <\/jats:p>","DOI":"10.1002\/advs.76371","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:47:43Z","timestamp":1783421263000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["RHINO: An Integrative Multi\u2010Omics Framework Linking Circadian Physiology to Precision Medicine"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4512-2821","authenticated-orcid":false,"given":"Ying","family":"Chen","sequence":"first","affiliation":[{"name":"Division of Diabetes Endocrinology, and Metabolism Department of Medicine Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengxuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Health Data Science Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dishu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Division of Diabetes Endocrinology, and Metabolism Department of Medicine Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Diabetes Endocrinology, and Metabolism Department of Medicine Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto E.","family":"L\u00f3pez\u2010Valiente","sequence":"additional","affiliation":[{"name":"Division of Diabetes Endocrinology, and Metabolism Department of Medicine Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Health Data Science Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cam Mong","family":"La","sequence":"additional","affiliation":[{"name":"Division of Diabetes Endocrinology, and Metabolism Department of Medicine Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella Beraldo","family":"Xavier","sequence":"additional","affiliation":[{"name":"Division of Diabetes Endocrinology, and Metabolism Department of Medicine Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean M.","family":"Hartig","sequence":"additional","affiliation":[{"name":"Division of Diabetes Endocrinology, and Metabolism Department of Medicine Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradip","family":"Saha","sequence":"additional","affiliation":[{"name":"Division of Diabetes Endocrinology, and Metabolism Department of Medicine Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Sun","sequence":"additional","affiliation":[{"name":"Division of Diabetes Endocrinology, and Metabolism Department of Medicine Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leng","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Health Data Science Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyin","family":"Guan","sequence":"additional","affiliation":[{"name":"Division of Diabetes Endocrinology, and Metabolism Department of Medicine Baylor College of Medicine  Houston Texas 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and 17beta\u2010estradiol Replacement in Rats and Mice: A Visual Demonstration","volume":"64","author":"Strom J. 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