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Wound age estimation based on next-generation sequencing: Fitting the optimal index system using machine learning
Institution:1. School of Forensic Medicine, Shanxi Medical University, 98 University Street, Yuci District, Jinzhong 030606, Shanxi, P.R. China;2. Department of Biomedical Sciences, College of Osteopathic Medicine, New York Institute of Technology, Old Westbury, NY 11568–8000, USA;1. Department of Forensic Genetics, Institute of Legal Medicine and Forensic Sciences, Charité - Universitätsmedizin Berlin, Germany;2. Department of Isotopic Geochemistry & Geochronology, Institute of Mineralogy, TU Bergakademie Freiberg, Germany;3. Project Medieval Space and Population, Landesdenkmalamt Berlin, Germany;4. Curt-Engelhorn-Center Archaeometry, Mannheim, Germany;1. People''s Public Security University of China, Beijing 100038, China;2. National Engineering Laboratory for Forensic Science, Key Laboratory of Forensic Genetics of Ministry of Public Security, Institute of Forensic Science, Ministry of Public Security, Beijing 100038, China;1. Faculdade de Ciências, Universidade do Porto, Portugal;2. i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal;3. IPATIMUP - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Portugal;4. Biologia, Laboratório de Polícia Científica da Polícia Judiciaria (LPC-PJ), Lisboa, Portugal;5. CMUP, Centro de Matemática da Universidade do Porto, Portugal;1. Beijing Institute of Microbiology and Epidemiology, 27 Taiping Road, Beijing 100850, PR China;2. Department of Pathology and Forensic Medicine, College of Medicine, Yanbian University, No. 977 Park Road, Jilin 133002, PR China
Abstract:Accurate estimation of the wound age is critical in investigating intentional injury cases. Establishing objective and reliable biological indicators to estimate wound age is still a significant challenge in forensic medicine. Therefore, exploring an objective, flexible, and reliable index system selection method for wound age estimation based on next-generation sequencing gene expression profiles is necessary. We randomly divided 63 Sprague-Dawley rats into a control group, seven experimental groups (n = 7 per group), and an external validation group. After rats in the experimental and external validation groups suffered contusions, we sacrificed them at 4, 8, 12, 16, 20, 24, and 48 h after contusion, respectively. We selected 54 genes with the most significant changes between adjacent time points after contusion and defined set A. The Hub genes with time-related expression patterns were set B, C, and D through next-generation sequencing and bioinformatics analysis. Four different machine learning classification algorithms, including logistic regression, support vector machine, multi-layer perceptron, and random forest were used to compare and verify the efficiency of four index systems to estimate the wound age. The best combination for wound age estimation is the Genes ascribed to set A combined with the random forest classification algorithm. The accuracy of external verification was 85.71%. Only one rat was incorrectly classified (4 h post-injury incorrectly classified as 8 h). This study demonstrated the potential advantage of the index system selection based on next-generation sequencing and bioinformatics analysis for wound age estimation.
Keywords:Forensic pathology  Next-generation sequencing  Wound age estimation  Skeletal muscle contusion  Index system  Machine learning algorithms
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