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Estimates of post-mortem interval (PMI), which often serve as pivotal evidence in forensic contexts, are fundamentally based on assessments of variability among diverse molecular markers (including proteins and metabolites), their correlations, and their temporal changes in post-mortem organisms. Nevertheless, the present approach to estimating the PMI is not comprehensive and exhibits poor performance. We developed an innovative approach that integrates multi-omics and artificial intelligence, using multimolecular, multimarker, and multidimensional information to accurately describe the intricate biological processes that occur after death, ultimately enabling inference of the PMI. Called the multi-omics stacking model (MOSM), it combines metabolomics, protein microarray electrophoresis, and fourier transform-infrared spectroscopy data. It shows improved prediction accuracy of the PMI, which is urgently needed in the forensic field. It achieved an accuracy of 0.93, generalized area under the receiver operating characteristic curve of 0.98, and minimum mean absolute error of 0.07. The MOSM integration framework not only considers multiple markers but also incorporates machine-learning models with distinct algorithmic principles. The diversity of biological mechanisms and algorithmic models further ensures the generalizability and robustness of PMI estimation.
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•A comprehensive framework was constructed to analyze the molecular markers detected from three omics.•The MOSM showed superior PMI estimation by effectively integrating diverse molecular markers’ change patterns.•The multi-omics procedure could be a novel tool for forensic and biomedical science.