{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T04:01:16Z","timestamp":1792555276495,"version":"4.5.0"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes, Digestive, and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 097053"],"award-info":[{"award-number":["R01 097053"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes, Digestive, and Kidney Diseases","doi-asserted-by":"publisher","award":["U24DK100845"],"award-info":[{"award-number":["U24DK100845"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes, Digestive, and Kidney Diseases","doi-asserted-by":"publisher","award":["UH3DK114907"],"award-info":[{"award-number":["UH3DK114907"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes, Digestive, and Kidney Diseases","doi-asserted-by":"publisher","award":["U2CDK114886"],"award-info":[{"award-number":["U2CDK114886"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes, Digestive, and Kidney Diseases","doi-asserted-by":"publisher","award":["K08 DK115891"],"award-info":[{"award-number":["K08 DK115891"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes, Digestive, and Kidney Diseases","doi-asserted-by":"publisher","award":["3T32DK007053-45S1"],"award-info":[{"award-number":["3T32DK007053-45S1"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes, Digestive, and Kidney Diseases","doi-asserted-by":"publisher","award":["2P30-DK-081943"],"award-info":[{"award-number":["2P30-DK-081943"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["U54DK083912"],"award-info":[{"award-number":["U54DK083912"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["U2CTR002818"],"award-info":[{"award-number":["U2CTR002818"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>Although membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome, the molecular characteristics of the kidney damage in MN remain poorly defined. In this study, the authors applied a machine-learning framework to predict diagnosis on the basis of gene expression in microdissected kidney tissue from patients with glomerulonephropathies. They found that MN has a glomerular transcriptional signature that distinguishes it from other glomerulonephropathies and identified a set of MN-specific genes differentially expressed across two independent cohorts and robustly recovered in an additional validation cohort. They also found the MN-specific genes are enriched in targets of transcription factor NF-\u03baB and are predominantly expressed in podocytes. This work provides a molecular snapshot of MN and elucidates transcriptional alterations specific to this disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Molecular characterization of nephropathies may facilitate pathophysiologic insight, development of targeted therapeutics, and transcriptome-based disease classification. Although membranous nephropathy (MN) is a common cause of adult-onset nephrotic syndrome, the molecular pathways of kidney damage in MN require further definition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We applied a machine-learning framework to predict diagnosis on the basis of gene expression from the microdissected kidney tissue of participants in the Nephrotic Syndrome Study Network (NEPTUNE) cohort. We sought to identify differentially expressed genes between participants with MN versus those of other glomerulonephropathies across the NEPTUNE and European Renal cDNA Bank (ERCB) cohorts, to find MN-specific gene modules in a kidney-specific functional network, and to identify cell-type specificity of MN-specific genes using single-cell sequencing data from reference nephrectomy tissue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Glomerular gene expression alone accurately separated participants with MN from those with other nephrotic syndrome etiologies. The top predictive classifier genes from NEPTUNE participants were also differentially expressed in the ERCB participants with MN. We identified a signature of 158 genes that are significantly differentially expressed in MN across both cohorts, finding 120 of these in a validation cohort. This signature is enriched in targets of transcription factor NF-\u03baB. Clustering these MN-specific genes in a kidney-specific functional network uncovered modules with functional enrichments, including in ion transport, cell projection morphogenesis, regulation of adhesion, and wounding response. Expression data from reference nephrectomy tissue indicated 43% of these genes are most highly expressed by podocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results suggest that, relative to other glomerulonephropathies, MN has a distinctive molecular signature that includes upregulation of many podocyte-expressed genes, provides a molecular snapshot of MN, and facilitates insight into MN\u2019s underlying pathophysiology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2021060784","type":"journal-article","created":{"date-parts":[[2022,5,11]],"date-time":"2022-05-11T02:10:11Z","timestamp":1652235011000},"page":"1208-1221","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":30,"title":["Molecular Characterization of Membranous 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Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6280-9639","authenticated-orcid":false,"given":"Rajasree","family":"Menon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Funk","sequence":"additional","affiliation":[{"name":"Center for Computational Biology, Flatiron Institute, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Wong","sequence":"additional","affiliation":[{"name":"Center for Computational Biology, Flatiron Institute, New York, New York"},{"name":"Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Lerner","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norifumi","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts"},{"name":"Division of Nephrology, Kanazawa Medical University, Uchinada, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Troyanskaya","sequence":"additional","affiliation":[{"name":"Center for Computational Biology, Flatiron Institute, New York, New York"},{"name":"Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey"},{"name":"Department of Computer Science, Princeton University, Princeton, New 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