{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:18:03Z","timestamp":1792016283747,"version":"4.4.0"},"reference-count":116,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014188","name":"National Research Foundation (NRF) of the Ministry of Science and ICT (MSIT) in Korea","doi-asserted-by":"publisher","award":["RS-2023-NR076560"],"award-info":[{"award-number":["RS-2023-NR076560"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"National Research Foundation (NRF) of the Ministry of Science and ICT (MSIT) in Korea","doi-asserted-by":"publisher","award":["RS-2024-00416536"],"award-info":[{"award-number":["RS-2024-00416536"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Multiple system atrophy (MSA) is a progressive neurodegenerative synucleinopathy. Differentiating MSA from other synucleinopathies, especially in the early stages, is challenging because of its overlapping symptoms with other forms of Parkinsonism. Thus, there is a pressing need to clarify the underlying biological mechanisms and identify specific biomarkers for MSA. The metabolic profile of cerebrospinal fluid (CSF) is known to be altered in MSA. To further investigate the biological mechanisms behind the metabolic changes, we created a network of altered CSF metabolites in patients with MSA and analysed these changes using bioinformatic software. Acknowledging the limitations of metabolomics, we incorporated proteomic data to improve the overall comprehensiveness of the study. Our in silico predictions showed elevated ROS, cytoplasmic inclusions, white matter demyelination, ataxia, and neurodegeneration, with ATP concentration, neurotransmitter release, and oligodendrocyte count predicted to be suppressed in MSA CSF samples. Machine learning and dimension reduction are important multi-omics approaches as they handle large amounts of data, identify patterns, and make predictions while reducing variance without information loss and generating easily visualised plots that help identify clusters, patterns, or outliers. Thus, integrated multiomics and machine learning approaches are essential for elucidating neurodegenerative mechanisms and identifying potential diagnostic biomarkers of MSA.<\/jats:p>","DOI":"10.3390\/cells14040265","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T10:25:57Z","timestamp":1739355957000},"page":"265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Integrative Analysis of Metabolome and Proteome in the Cerebrospinal Fluid of Patients with Multiple System Atrophy"],"prefix":"10.3390","volume":"14","author":[{"given":"Nimisha Pradeep","family":"George","sequence":"first","affiliation":[{"name":"Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea"},{"name":"Department of Physiology, Ajou University School of Medicine, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0045-1958","authenticated-orcid":false,"given":"Minjun","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea"},{"name":"Department of Physiology, Ajou University School of Medicine, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1297-7455","authenticated-orcid":false,"given":"Yong Eun","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea"},{"name":"Department of Physiology, Ajou University School of Medicine, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5914-2471","authenticated-orcid":false,"given":"Seok Gi","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea"},{"name":"Department of Physiology, Ajou University School of Medicine, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9422-1880","authenticated-orcid":false,"given":"Ji Su","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea"},{"name":"Department of Physiology, Ajou University School of Medicine, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0975-4211","authenticated-orcid":false,"given":"Sang Seop","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Inje University College of Medicine, Busan 50834, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1299-9478","authenticated-orcid":false,"given":"Gwang","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea"},{"name":"Department of Physiology, Ajou University School of Medicine, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1056\/NEJMra1311488","article-title":"Multiple-system atrophy","volume":"372","author":"Fanciulli","year":"2015","journal-title":"N. 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