{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:17:13Z","timestamp":1785197833906,"version":"3.55.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T00:00:00Z","timestamp":1694476800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["860329"],"award-info":[{"award-number":["860329"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["764474"],"award-info":[{"award-number":["764474"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["322900939"],"award-info":[{"award-number":["322900939"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["01EK2105A-E"],"award-info":[{"award-number":["01EK2105A-E"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000921","name":"COST","doi-asserted-by":"publisher","award":["CA21165"],"award-info":[{"award-number":["CA21165"]}],"id":[{"id":"10.13039\/501100000921","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and hypothesis<\/jats:title>\n                  <jats:p>Specific urinary peptides hold information on disease pathophysiology, which, in combination with artificial intelligence, could enable non-invasive assessment of chronic kidney disease (CKD) aetiology. Existing approaches are generally specific for the diagnosis of single aetiologies. We present the development of models able to simultaneously distinguish and spatially visualize multiple CKD aetiologies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The urinary peptide data of 1850 healthy control (HC) and CKD [diabetic kidney disease (DKD), immunoglobulin A nephropathy (IgAN) and vasculitis] participants were extracted from the Human Urinary Proteome Database. Uniform manifold approximation and projection (UMAP) coupled to a support vector machine algorithm was used to generate multi-peptide models to perform binary (DKD, HC) and multiclass (DKD, HC, IgAN, vasculitis) classifications. This pipeline was compared with the current state-of-the-art single-aetiology CKD urinary peptide models.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In an independent test set, the developed models achieved 90.35% and 70.13% overall predictive accuracies, respectively, for the binary and the multiclass classifications. Omitting the UMAP step led to improved predictive accuracies (96.14% and 85.06%, respectively). As expected, the HC class was distinguished with the highest accuracy. The different classes displayed a tendency to form distinct clusters in the 3D space based on their disease state.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Urinary peptide data present an effective basis for CKD aetiology differentiation using machine learning models. Although adding the UMAP step to the models did not improve prediction accuracy, it may provide a unique visualization advantage. Additional studies are warranted to further validate the pipeline's clinical potential as well as to expand it to other CKD aetiologies and also other diseases.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ndt\/gfad200","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T06:30:17Z","timestamp":1694500217000},"page":"453-462","source":"Crossref","is-referenced-by-count":19,"title":["Urinary peptidomic liquid biopsy for non-invasive differential diagnosis of chronic kidney disease"],"prefix":"10.1093","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1726-0241","authenticated-orcid":false,"given":"Emmanouil","family":"Mavrogeorgis","sequence":"first","affiliation":[{"name":"Mosaiques Diagnostics GmbH , Hannover , Germany"},{"name":"Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University Hospital , Aachen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7806-4846","authenticated-orcid":false,"given":"Tianlin","family":"He","sequence":"additional","affiliation":[{"name":"Mosaiques Diagnostics GmbH , Hannover , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0323-0306","authenticated-orcid":false,"given":"Harald","family":"Mischak","sequence":"additional","affiliation":[{"name":"Mosaiques Diagnostics GmbH , Hannover , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8917-2412","authenticated-orcid":false,"given":"Agnieszka","family":"Latosinska","sequence":"additional","affiliation":[{"name":"Mosaiques Diagnostics GmbH , Hannover , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3284-5713","authenticated-orcid":false,"given":"Antonia","family":"Vlahou","sequence":"additional","affiliation":[{"name":"Center of Systems Biology, Biomedical Research Foundation of the Academy of Athens , Athens , Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7471-372X","authenticated-orcid":false,"given":"Joost P","family":"Schanstra","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), U1297, Institute of Cardiovascular and Metabolic Disease , Toulouse , France"},{"name":"Universit\u00e9 Toulouse III Paul-Sabatier , Toulouse , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9933-8364","authenticated-orcid":false,"given":"Lorenzo","family":"Catanese","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Angiology and Rheumatology, Klinikum Bayreuth GmbH , Bayreuth , Germany"},{"name":"Kuratorium for Dialysis and Transplantation (KfH) Bayreuth , Bayreuth , Germany"},{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg , Erlangen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6116-8315","authenticated-orcid":false,"given":"Kerstin","family":"Amann","sequence":"additional","affiliation":[{"name":"Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-University of Erlangen-N\u00fcrnberg , Erlangen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7175-5062","authenticated-orcid":false,"given":"Tobias B","family":"Huber","sequence":"additional","affiliation":[{"name":"III. Department of Medicine, University Medical Center Hamburg-Eppendorf , Hamburg , Germany"},{"name":"Hamburg Center for Kidney Health (HCKH), University Medical Center Hamburg-Eppendorf , Hamburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1907-825X","authenticated-orcid":false,"given":"Joachim","family":"Beige","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases\/Tropical Medicine, Nephrology\/KfH Renal Unit and Rheumatology, St Georg Hospital Leipzig , Leipzig , Germany"},{"name":"Kuratorium for Dialysis and Transplantation (KfH) Renal Unit, St Georg Hospital , Leipzig , Germany"},{"name":"Department of Internal Medicine II, Martin-Luther-University Halle\/Wittenberg , Halle (Saale) , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5761-2911","authenticated-orcid":false,"given":"Harald D","family":"Rupprecht","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Angiology and Rheumatology, Klinikum Bayreuth GmbH , Bayreuth , Germany"},{"name":"Kuratorium for Dialysis and Transplantation (KfH) Bayreuth , Bayreuth , Germany"},{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg , Erlangen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1407-2534","authenticated-orcid":false,"given":"Justyna","family":"Siwy","sequence":"additional","affiliation":[{"name":"Mosaiques Diagnostics GmbH , Hannover , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,9,11]]},"reference":[{"key":"2024022807040299100_bib1","doi-asserted-by":"crossref","first-page":"100438","DOI":"10.1016\/j.lanepe.2022.100438","article-title":"Prevalence, outcomes, and cost of chronic kidney disease in a contemporary population of 2\u00b74 million patients from 11 countries: the CaReMe CKD study","volume":"20","author":"Sundstr\u00f6m","year":"2022","journal-title":"Lancet Reg Health Eur"},{"key":"2024022807040299100_bib2","doi-asserted-by":"crossref","first-page":"287","DOI":"10.5527\/wjn.v3.i4.287","article-title":"Renal biopsy practice: what is the gold standard?","volume":"3","author":"Brachemi","year":"2014","journal-title":"World J Nephrol"},{"key":"2024022807040299100_bib3","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1093\/ndt\/gfy337","article-title":"Reproducibility of the Oxford classification of immunoglobulin A nephropathy, impact of biopsy scoring on treatment allocation and clinical relevance of disagreements: evidence from the VALidation of IGA study cohort","volume":"34","author":"Bellur","year":"2019","journal-title":"Nephrol Dial Transplant"},{"key":"2024022807040299100_bib4","doi-asserted-by":"crossref","first-page":"a005462","DOI":"10.1101\/mcs.a005462","article-title":"Diagnostic utility of genetic testing in patients undergoing renal biopsy","volume":"6","author":"Benson","year":"2020","journal-title":"Cold Spring Harb Mol Case Stud"},{"key":"2024022807040299100_bib5","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1159\/000522226","article-title":"Genetic etiologies for chronic kidney disease revealed through next-generation renal gene panel","volume":"53","author":"Bleyer","year":"2022","journal-title":"Am J Nephrol"},{"key":"2024022807040299100_bib6","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.kint.2018.02.027","article-title":"A kidney-disease gene panel allows a comprehensive genetic diagnosis of cystic and glomerular inherited kidney diseases","volume":"94","author":"Bullich","year":"2018","journal-title":"Kidney Int"},{"key":"2024022807040299100_bib7","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1093\/ndt\/gfab019","article-title":"Clinical utility of genetic testing in early-onset kidney disease: seven genes are the main players","volume":"37","author":"Domingo-Gallego","year":"2022","journal-title":"Nephrol Dial Transplant"},{"key":"2024022807040299100_bib8","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1093\/ndt\/gfac163","article-title":"Alport syndrome and autosomal dominant tubulointerstitial kidney disease frequently underlie end-stage renal disease of unknown origin\u2014a single-center analysis","volume":"37","author":"Leenen","year":"2022","journal-title":"Nephrol Dial Transplant"},{"key":"2024022807040299100_bib9","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1111\/cge.13869","article-title":"Clinical application of a phenotype-based NGS panel for differential diagnosis of inherited kidney disease and beyond","volume":"99","author":"Oh","year":"2021","journal-title":"Clin Genet"},{"key":"2024022807040299100_bib10","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.kint.2019.01.038","article-title":"Value of renal gene panel diagnostics in adults waiting for kidney transplantation due to undetermined end-stage renal disease","volume":"96","author":"Ottlewski","year":"2019","journal-title":"Kidney Int"},{"key":"2024022807040299100_bib11","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1007\/s00467-021-05374-4","article-title":"A multidisciplinary nephrogenetic referral clinic for children and adults\u2014diagnostic achievements and insights","volume":"37","author":"Pode-Shakked","year":"2022","journal-title":"Pediatr Nephrol"},{"key":"2024022807040299100_bib12","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.1007\/s00467-022-05846-1","article-title":"Clinical and diagnostic utility of genomic sequencing for children referred to a Kidney Genomics Clinic with microscopic haematuria","volume":"38","author":"Shanks","year":"2023","journal-title":"Pediatr Nephrol"},{"key":"2024022807040299100_bib13","doi-asserted-by":"crossref","first-page":"4802","DOI":"10.3390\/ijms21134802","article-title":"Proteomics-based machine learning approach as an alternative to conventional biomarkers for differential diagnosis of chronic kidney diseases","volume":"21","author":"Glazyrin","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2024022807040299100_bib14","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/j.ekir.2019.07.009","article-title":"Pilot study of renal urinary biomarkers for diagnosis of CKD of uncertain etiology","volume":"4","author":"Fernando","year":"2019","journal-title":"Kidney Int Rep"},{"key":"2024022807040299100_bib15","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1002\/ejhf.2195","article-title":"Urinary peptides in heart failure: a link to molecular pathophysiology","volume":"23","author":"He","year":"2021","journal-title":"Eur J Heart Fail"},{"key":"2024022807040299100_bib16","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1002\/prca.201300038","article-title":"Clinical applications of capillary electrophoresis coupled to mass spectrometry in biomarker discovery: focus on bladder cancer","volume":"7","author":"Latosinska","year":"2013","journal-title":"Proteomics Clin Appl"},{"key":"2024022807040299100_bib17","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.1002\/elps.201900091","article-title":"Peptidomics and proteomics based on CE-MS as a robust tool in clinical application: the past, the present, and the future","volume":"40","author":"Latosinska","year":"2019","journal-title":"Electrophoresis"},{"key":"2024022807040299100_bib18","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1080\/14789450.2021.1908893","article-title":"Understanding glomerular diseases through proteomics","volume":"18","author":"Mavrogeorgis","year":"2021","journal-title":"Expert Rev Proteomics"},{"key":"2024022807040299100_bib19","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1002\/prca.200900189","article-title":"Comprehensive human urine standards for comparability and standardization in clinical proteome analysis","volume":"4","author":"Mischak","year":"2010","journal-title":"Proteomics Clin Appl"},{"key":"2024022807040299100_bib20","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.clinbiochem.2012.09.025","article-title":"Technical aspects and inter-laboratory variability in native peptide profiling: the CE-MS experience","volume":"46","author":"Mischak","year":"2013","journal-title":"Clin Biochem"},{"key":"2024022807040299100_bib21","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1002\/elps.201300327","article-title":"Comparison of CE-MS\/MS and LC-MS\/MS sequencing demonstrates significant complementarity in natural peptide identification in human urine","volume":"35","author":"Klein","year":"2014","journal-title":"Electrophoresis"},{"key":"2024022807040299100_bib22","doi-asserted-by":"crossref","first-page":"7260","DOI":"10.3390\/molecules26237260","article-title":"Reproducibility evaluation of urinary peptide detection using CE-MS","volume":"26","author":"Mavrogeorgis","year":"2021","journal-title":"Molecules"},{"key":"2024022807040299100_bib23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2105-11-594","article-title":"Addressing the challenge of defining valid proteomic biomarkers and classifiers","volume":"11","author":"Dakna","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"2024022807040299100_bib24","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1093\/ndt\/gfaa307","article-title":"Urine proteomics for prediction of disease progression in patients with IgA nephropathy","volume":"37","author":"Rudnicki","year":"2021","journal-title":"Nephrol Dial Transplant"},{"key":"2024022807040299100_bib25","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1074\/mcp.M110.001917","article-title":"Naturally occurring human urinary peptides for use in diagnosis of chronic kidney disease","volume":"9","author":"Good","year":"2010","journal-title":"Mol Cell Proteomics"},{"key":"2024022807040299100_bib26","article-title":"The long path towards implementation of clinical proteomics: exemplified based on CKD273","volume":"11","author":"Nkuipou-Kenfack","year":"2017","journal-title":"Proteomics Clin Appl"},{"key":"2024022807040299100_bib27","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S2213-8587(20)30026-7","article-title":"Early detection of diabetic kidney disease by urinary proteomics and subsequent intervention with spironolactone to delay progression (PRIORITY): a prospective observational study and embedded randomised placebo-controlled trial","volume":"8","author":"Tofte","year":"2020","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2024022807040299100_bib28","first-page":"2079","article-title":"Noninvasive diagnosis of chronic kidney diseases using urinary proteome analysis","volume":"32","author":"Siwy","year":"2017","journal-title":"Nephrol Dial Transplant"},{"key":"2024022807040299100_bib29","article-title":"UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction","author":"McInnes","year":"2020"},{"key":"2024022807040299100_bib30","doi-asserted-by":"crossref","first-page":"861","DOI":"10.21105\/joss.00861","article-title":"UMAP: Uniform Manifold Approximation and Projection","volume":"3","author":"McInnes","year":"2018","journal-title":"J Open Source Softw"},{"key":"2024022807040299100_bib31","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1613\/jair.953","article-title":"SMOTE: Synthetic Minority Over-sampling Technique","volume":"16","author":"Chawla","year":"2002","journal-title":"J Artif Intell Res"},{"key":"2024022807040299100_bib32","article-title":"UMAP","author":"McInnes","year":"2018"},{"key":"2024022807040299100_bib33","article-title":"Understanding UMAP","author":"Coenen"},{"key":"2024022807040299100_bib34","volume-title":"Dynamic programming","author":"Bellman","year":"1957"},{"key":"2024022807040299100_bib35","first-page":"117","volume-title":"The Application of Bayesian Methods for Seeking the Extremum","author":"Mockus","year":"1978"}],"container-title":["Nephrology Dialysis Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ndt\/advance-article-pdf\/doi\/10.1093\/ndt\/gfad200\/51954987\/gfad200.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ndt\/article-pdf\/39\/3\/453\/56757267\/gfad200.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ndt\/article-pdf\/39\/3\/453\/56757267\/gfad200.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T07:12:26Z","timestamp":1709104346000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ndt\/article\/39\/3\/453\/7269226"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,11]]},"references-count":35,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,9,11]]},"published-print":{"date-parts":[[2024,2,28]]}},"URL":"https:\/\/doi.org\/10.1093\/ndt\/gfad200","relation":{},"ISSN":["0931-0509","1460-2385"],"issn-type":[{"value":"0931-0509","type":"print"},{"value":"1460-2385","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,3]]},"published":{"date-parts":[[2023,9,11]]}}}