Preliminary Metabolomic Profiling of the Vitreous Humor from Hypothermia Fatalities

Abstract

The postmortem diagnosis of hypothermia fatalities is often complex due to the absence of pathognomonic lesions and biomarkers. In this study, potential novel biomarkers of hypothermia fatalities were searched in the vitreous humor of known cases of hypothermia fatalities (n = 20) compared to control cases (n = 16), using a targeted metabolomics approach allowing quantitative detection of 188 metabolites. A robust discriminant model with good predictivity was obtained with the supervised OPLS-DA multivariate analysis, showing a distinct separation between the hypothermia and control groups. This signature was characterized by the decreased concentrations of five metabolites (methionine sulfoxide, tryptophan, phenylalanine, alanine, and ornithine) and the increased concentration of 28 metabolites (21 phosphatidylcholines, 3 sphingomyelins, spermine, citrulline, acetylcarnitine, and hydroxybutyrylcarnitine) in hypothermia fatalities compared to controls. The signature shows similarities with already identified features in serum such as the altered concentrations of tryptophan, acylcarnitines, and unsaturated phosphatidylcholines, revealing a highly significant increased activity of methionine sulfoxide reductase, attested by a low methionine sulfoxide-to-methionine ratio. Our results show a preliminary metabolomics signature of hypothermia fatalities in the vitreous humor, highlighting an increased methionine sulfoxide reductase activity.

From flesh to bones: Multi‐omics approaches in forensic science

“…However, the study highlighted biases that could be introduced by sample collection time, limited inter-individual variability in rats compared to humans, and low metabolic coverage offered by GC-MS in comparison with LC-MS [171]. Vitreous humor (VH), a target fluid for metabolomic analysis, was utilized in a targeted assay to compare cases of hypothermia fatalities (n = 20) to control cases (n = 16) by Rousseau et al [172]. Orthogonal partial least-squares discriminant analysis (OPLS-DA) was applied to the profiles of 188 metabolites.…”

“…This analysis captured 72% of the correlation between variables and 89% of the variance, with a predictive ability of Q 2 = 0.51, highlighting the effectiveness of the technique. Furthermore, good markers were identified in methionine sulfoxide, methionine, and acetylcarnitine [172].…”

“…Vitreous humor (VH), a target fluid for metabolomic analysis, was utilized in a targeted assay to compare cases of hypothermia fatalities ( n = 20) to control cases ( n = 16) by Rousseau et al. [172]. Orthogonal partial least‐squares discriminant analysis (OPLS‐DA) was applied to the profiles of 188 metabolites.…”

Small molecule metabolites: discovery of biomarkers and therapeutic targets

“… 568 – 570 Both un-targeted and targeted approach have also been conducted identifying specific metabolites or predictor biomarkers which were linked to metabolic alterations. 571 – 574 …”

Postmortem metabolomics as a high-throughput cause-of-death screening tool for human death investigations

“…Previously, the utility of postmortem metabolomics has been demonstrated by proposing metabolic fingerprints, from femoral blood samples, for various CoD including pneumonia, 14 oxycodone intoxications, 15 and insulin intoxications. 16 Postmortem metabolomics has also identified metabolic fingerprints for hypothermia, using vitreous humor samples, 17 as well as differentiating central-nervous-system-related deaths based on the cerebrospinal fluid metabolome. 18 Postmortem redistribution of exogenous substances has also been investigated using postmortem metabolomics.…”