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Although etiologically different cholestasis displays similar symptoms, diverse factors can contribute to the progression of the disease and determine the appropriate therapeutic option. Therefore, stratifying cholestatic patients is essential for the development of tailor-made treatment strategies. Here, we have analyzed the liver proteome from cholestatic patients of different etiology. In total, 7161 proteins were identified and quantified, of which 263 were differentially expressed between control and cholestasis groups. These differential proteins point to deregulated cellular processes that explain part of the molecular framework of cholestasis progression. However, the clustering of different cholestasis types was limited. Therefore, a machine learning pipeline was designed to identify a panel of 20 differential proteins that segregate different cholestasis groups with high accuracy and sensitivity. In summary, proteomics combined with machine learning algorithms provides valuable insights into the molecular mechanisms of cholestasis progression and a panel of proteins to discriminate across different types of cholestasis. This strategy may prove useful in developing precision medicine approaches for patient care.<\/jats:p>","DOI":"10.3390\/ijms25073684","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T11:34:58Z","timestamp":1711452898000},"page":"3684","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Discrimination of Etiologically Different Cholestasis by Modeling Proteomics Datasets"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1842-8449","authenticated-orcid":false,"given":"Laura","family":"Guerrero","sequence":"first","affiliation":[{"name":"Centro Nacional de Biotecnolog\u00eda (CNB-CSIC), c\/Darwin, 3, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Vindel-Alfageme","sequence":"additional","affiliation":[{"name":"Centro Nacional de Biotecnolog\u00eda (CNB-CSIC), c\/Darwin, 3, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loreto","family":"Hierro","sequence":"additional","affiliation":[{"name":"IdiPAZ, Instituto de Investigaci\u00f3n Sanitaria (Health Research Institute), Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9391-1409","authenticated-orcid":false,"given":"Luiz","family":"Stark","sequence":"additional","affiliation":[{"name":"IdiPAZ, Instituto de Investigaci\u00f3n Sanitaria (Health Research Institute), Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6663-0350","authenticated-orcid":false,"given":"David","family":"Vicent","sequence":"additional","affiliation":[{"name":"IdiPAZ, Instituto de Investigaci\u00f3n Sanitaria (Health Research Institute), Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9473-283X","authenticated-orcid":false,"given":"Carlos \u00d3scar S.","family":"Sorzano","sequence":"additional","affiliation":[{"name":"Centro Nacional de Biotecnolog\u00eda (CNB-CSIC), c\/Darwin, 3, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0231-5159","authenticated-orcid":false,"given":"Fernando J.","family":"Corrales","sequence":"additional","affiliation":[{"name":"Centro Nacional de Biotecnolog\u00eda (CNB-CSIC), c\/Darwin, 3, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1002\/cld.894","article-title":"The Pathophysiology of Cholestasis and Its Relevance to Clinical Practice","volume":"15","author":"Onofrio","year":"2020","journal-title":"Clin. 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