biostudies-literatureAlex SFonds Wetenschappelijk OnderzoekBijzonder Onderzoeksfonds UGent4888-4899https://www.ebi.ac.uk/biostudies/studies/S-EPMC12501993biostudies-literatureUnknown24(10)Forensic DNA analysis is well established for phenotyping, providing valuable investigative leads. Proteomics, the large-scale study of proteins, is emerging as a complementary tool to DNA analysis, particularly for enhancing the evidential value of traces. This study explores the potential of proteomics to extract phenotypic traits from whole blood, using the estimation of biological sex as a starting point. Using LC-MS/MS, proteomes from 100 whole blood samples of known sex were analyzed to develop a biological sex classifier. Cross-validation of the model highlighted the model's ability to achieve accurate classification, identifying key peptides, such as those from pregnancy zone protein and ceruloplasmin, as critical markers. To test real-world applicability, mock case samples were geJournal of proteome researchPotential of Proteomics in Forensic Phenotyping: A Focus on Biological Sex Estimation.PMC12501993FWO 12A6L24NFWO 1294822NBOF21/DOC/076FWO 12E9716NDeforce DClerck LDennis RSAlmey RBouwmeester RPuit MTytgat OAlex SDhaenens MfalsePotential of Proteomics in Forensic Phenotyping: A Focus on Biological Sex Estimation.Forensic DNA analysis is well established for phenotyping, providing valuable investigative leads. Proteomics, the large-scale study of proteins, is emerging as a complementary tool to DNA analysis, particularly for enhancing the evidential value of traces. This study explores the potential of proteomics to extract phenotypic traits from whole blood, using the estimation of biological sex as a starting point. Using LC-MS/MS, proteomes from 100 whole blood samples of known sex were analyzed to develop a biological sex classifier. Cross-validation of the model highlighted the model's ability to achieve accurate classification, identifying key peptides, such as those from pregnancy zone protein and ceruloplasmin, as critical markers. To test real-world applicability, mock case samples were ge2025-01-01T00:00:00Z2025 Oct2026-06-04T06:21:07.928Z2026-05-06T03:12:32.046ZS-EPMC125019934089981010.1021/acs.jproteome.5c00098