{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T11:31:20Z","timestamp":1771932680187,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"BK21FOUR Program","award":["5120200513755"],"award-info":[{"award-number":["5120200513755"]}]},{"DOI":"10.13039\/501100014188","name":"the Bio & Medical Technology Development Program of the NRF","doi-asserted-by":"publisher","award":["2020M3E5D9080791"],"award-info":[{"award-number":["2020M3E5D9080791"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Basic Science Research Program","award":["RS-2023-00245859"],"award-info":[{"award-number":["RS-2023-00245859"]}]},{"DOI":"10.13039\/501100014188","name":"NRF","doi-asserted-by":"publisher","award":["NRF-2022R1A2C2091831"],"award-info":[{"award-number":["NRF-2022R1A2C2091831"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Autism Spectrum Disorder (ASD) is a biologically heterogeneous neurodevelopmental condition, presenting a major barrier to the identification of robust and translatable molecular biomarkers. Here, we employ a cross-species proteomic framework to identify conserved protein signatures associated with ASD. Quantitative proteomic profiling of brain and serum from CNTNAP2 knockout mice, integrated with serum proteomes from individuals with ASD, revealed 132 proteins consistently dysregulated across species. Functional pathway analyses implicated coordinated alterations in lipid metabolism, synaptic signaling, and immune regulation. To prioritize diagnostically informative candidates, we applied machine learning-based feature selection and identified a minimal panel of ten proteins (COL1A1, ITIH4, CLU, NID1, C5, MASP1, PON1, PLTP, HSPA5, and FETUB) that robustly discriminated ASD from control samples. Gene ontology and KEGG pathway analyses highlighted enrichment of immune regulatory pathways, synaptic transmission, oxidative stress responses, and lipid metabolic processes, consistent with emerging models linking neuroimmune dysregulation and metabolic imbalance to ASD pathophysiology. An XGBClassifier trained on this biomarker panel achieved strong performance in independent test sets (AUC = 0.75). Together, these findings establish cross-species proteomic integration combined with machine learning as a powerful strategy for uncovering conserved, biologically grounded biomarkers in ASD, providing a framework for future validation and translational development.<\/jats:p>","DOI":"10.3390\/biom16030340","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T10:14:44Z","timestamp":1771928084000},"page":"340","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unveiling Diagnostic Biomarkers in Autism: A Comparative Proteome Analysis of CNTNAP2 Knockout Mice and Human ASD Patients"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3441-4753","authenticated-orcid":false,"given":"Andrew","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6244-4106","authenticated-orcid":false,"given":"Ara","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiyeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leandro Val","family":"Sayson","sequence":"additional","affiliation":[{"name":"Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, 815 Hwarang-ro, Nowon-gu, Seoul 01795, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9110-2963","authenticated-orcid":false,"given":"Hyun Ju","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hanyang University College of Medicine, Seoul 04763, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Hoon","family":"Cheong","sequence":"additional","affiliation":[{"name":"Institute for New Drug Development, School of Pharmacy, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si 54896, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7686-7167","authenticated-orcid":false,"given":"Hee Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, 815 Hwarang-ro, Nowon-gu, Seoul 01795, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2403-3291","authenticated-orcid":false,"given":"Bung Nyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Science, College of Medicine, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0615-7397","authenticated-orcid":false,"given":"Eugene C.","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1001\/jama.2022.23661","article-title":"Autism Spectrum Disorder: A Review","volume":"329","author":"Hirota","year":"2023","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e20193447","DOI":"10.1542\/peds.2019-3447","article-title":"Identification, evaluation, and management of children with autism spectrum disorder","volume":"145","author":"Hyman","year":"2020","journal-title":"Pediatrics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1038\/35103559","article-title":"Genetics of austim: Complex aetiology for a heterogeneous disorder","volume":"2","author":"Folstein","year":"2001","journal-title":"Nat. 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