{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:44:02Z","timestamp":1793727842646,"version":"4.6.1"},"reference-count":59,"publisher":"American Society for Clinical Investigation","issue":"5","license":[{"start":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T00:00:00Z","timestamp":1741564800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["P30DK081943,U54DK137314"],"award-info":[{"award-number":["P30DK081943,U54DK137314"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Michigan Health System and Peking University Health Sciences Center Joint Institute for Translational and Clinical Research","award":["U054401"],"award-info":[{"award-number":["U054401"]}],"id":[{"id":"https:\/\/ror.org\/01zcpa714","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,10]]},"abstract":"<jats:p>Chronic kidney diseases (CKDs) are a global health concern, necessitating a comprehensive understanding of their complex pathophysiology. This study explores the use of 2 complementary multidimensional -omics data integration methods to elucidate mechanisms of CKD progression as a proof of concept. Baseline biosamples from 37 participants with CKD in the Clinical Phenotyping and Resource Biobank Core (C-PROBE) cohort with prospective longitudinal outcome data ascertained over 5 years were used to generate molecular profiles. Tissue transcriptomic, urine and plasma proteomic, and targeted urine metabolomic profiling were integrated using 2 orthogonal multi-omics data integration approaches, one unsupervised and the other supervised. Both integration methods identified 8 urinary proteins significantly associated with long-term outcomes, which were replicated in an adjusted survival model using 94 samples from an independent validation group in the same cohort. The 2 methods also identified 3 shared enriched pathways: the complement and coagulation cascades, cytokine\u2013cytokine receptor interaction pathway, and the JAK\/STAT signaling pathway. Use of different multiscalar data integration strategies on the same data enabled identification and prioritization of disease mechanisms associated with CKD progression. Approaches like this will be invaluable with the expansion of high-dimension data in kidney diseases.<\/jats:p>","DOI":"10.1172\/jci.insight.186070","type":"journal-article","created":{"date-parts":[[2025,3,9]],"date-time":"2025-03-09T14:00:53Z","timestamp":1741528853000},"source":"Crossref","is-referenced-by-count":24,"title":["Leveraging complementary multi-omics data integration methods for mechanistic insights in kidney diseases"],"prefix":"10.1172","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5349-7960","authenticated-orcid":true,"given":"Fadhl","family":"Alakwaa","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Das","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, M\u00e5l\u00f8v, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arindam","family":"Majumdar","sequence":"additional","affiliation":[{"name":"Eli Lilly & Co., Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viji","family":"Nair","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0548-3967","authenticated-orcid":true,"given":"Damian","family":"Fermin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asim B.","family":"Dey","sequence":"additional","affiliation":[{"name":"Eli Lilly & Co., Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3868-6469","authenticated-orcid":true,"given":"Timothy","family":"Slidel","sequence":"additional","affiliation":[{"name":"Biopharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9456-1364","authenticated-orcid":true,"given":"Dermot F.","family":"Reilly","sequence":"additional","affiliation":[{"name":"Johnson & Johnson, New Brunswick, New Jersey, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Myshkin","sequence":"additional","affiliation":[{"name":"Johnson & Johnson, New Brunswick, New Jersey, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin L.","family":"Duffin","sequence":"additional","affiliation":[{"name":"Eli Lilly & Co., Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Eli Lilly & Co., Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3711-2984","authenticated-orcid":true,"given":"Markus","family":"Bitzer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subramaniam","family":"Pennathur","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank C.","family":"Brosius","sequence":"additional","affiliation":[{"name":"University of Arizona, Tucson, Arizona, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4064-0582","authenticated-orcid":true,"given":"Matthias","family":"Kretzler","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Karihaloo","sequence":"additional","affiliation":[{"name":"Novo Nordisk Research Center Seattle, Inc, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8578-3443","authenticated-orcid":true,"given":"Sean","family":"Eddy","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,3,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2022.12.001"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011303"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808400"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011489"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1515920"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1811744"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2025845"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2022.10.023"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2021.10.004"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2024.01.012"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-16341-w"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-021-07876-9"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-022-01520-x"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01965"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2021.0042"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27061904"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/database\/baac052"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/metabo12100949"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2022.08.005"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1237-9"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-020-01376-x"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts655"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.05.082"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-020-02015-1"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.15252\/msb.20178124"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty1054"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02953-4"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2018.06.002"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.0000000000000141"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2017.52"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-024-00868-4"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1172\/JCI11837"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013080906"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3390\/metabo9040076"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.036823"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01380-0"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2021.0125"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.12934"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-0699"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.7861\/clinmed.2019-0452"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfx377"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-08492-y"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05769-3"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2021040538"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-212935"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aac7071"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-150-9-200905050-00006"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/hvab278"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015004"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005752"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.90"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-128"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw377"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3715"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac963"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1002\/pro.4172"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-022-00710-w"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp356"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/186070\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T20:23:14Z","timestamp":1779135794000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/186070"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,10]]},"references-count":59,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,1,21]]},"published-print":{"date-parts":[[2025,3,10]]}},"alternative-id":["10.1172\/jci.insight.186070"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.186070","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,10]]},"article-number":"e186070"}}