Postmortem metabolomics as a high-throughput cause-of-death screening tool for human death investigations
Autopsy rates are declining globally, impacting cause-of-death (CoD) diagnoses and quality control. Postmortem metabolomics was evaluated for CoD screening using 4,282 human cases, encompassing CoD groups: acidosis, drug intoxication, hanging, ischemic heart disease (IHD), and pneumonia. Cases were...
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Veröffentlicht in: | iScience 2024-05, Vol.27 (5), p.109794-109794, Article 109794 |
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Sprache: | eng |
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Zusammenfassung: | Autopsy rates are declining globally, impacting cause-of-death (CoD) diagnoses and quality control. Postmortem metabolomics was evaluated for CoD screening using 4,282 human cases, encompassing CoD groups: acidosis, drug intoxication, hanging, ischemic heart disease (IHD), and pneumonia. Cases were split 3:1 into training and test sets. High-resolution mass spectrometry data from femoral blood were analyzed via orthogonal-partial least squares discriminant analysis (OPLS-DA) to discriminate CoD groups. OPLS-DA achieved an R2 = 0.52 and Q2 = 0.30, with true-positive prediction rates of 68% and 65% for training and test sets, respectively, across all groups. Specificity-optimized thresholds predicted 56% of test cases with a unique CoD, average 45% sensitivity, and average 96% specificity. Prediction accuracies varied: 98.7% for acidosis, 80.5% for drug intoxication, 81.6% for hanging, 73.1% for IHD, and 93.6% for pneumonia. This study demonstrates the potential of large-scale postmortem metabolomics for CoD screening, offering high specificity and enhancing throughput and decision-making in human death investigations.
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•Postmortem metabolomics successfully discriminates five cause-of-death (CoD) groups•Training and test sets resulted in true-positive prediction values of 68% and 65%•Specificity optimization yielded 73%–99% prediction accuracies for the CoD groups•Postmortem metabolomics shows potential for large-scale CoD screening
Death; Human; Biocomputational method; Metabolomics |
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ISSN: | 2589-0042 2589-0042 |
DOI: | 10.1016/j.isci.2024.109794 |