Post-Mortem Metabolomics: A Novel Approach in Clinical Biomarker Discovery and a Potential Tool in Death Investigations

Metabolomics
can be defined as the scientific field aiming at characterizing
all low-weight molecules (so-called metabolites) in a biological system.
At the time of death, the level and type of metabolites present will
most likely reflect the events leading up to death.In this proof of
concept study, we investigated the potential of post-mortem metabolomics
by identifying post-mortem biomarkers, correlated these identified
biomarkers with those reported in clinical metabolomics studies, and
finally validated the models predictability of unknown autopsy cases.
In this post-mortem metabolomics setting, ultra-high performance liquid
chromatography-quadrupole time-of-flight mass spectrometry data from
404 post-mortem samples, including pneumonia cases and control cases,
were processed using XCMS (R). Potential biomarkers were evaluated
using principal component analysis and orthogonal partial least squares-discriminant
analysis. Biomarkers were putatively annotated using an in-house database
and the online databases METLIN and HMDB. The results showed that
clear group separation was observed between pneumonia cases and control
cases. The metabolites responsible for group separation belonged to
a broad set of biological classes, such as amino acids, carnitines,
lipids, nicotinamides, nucleotides, and steroids. Many of these metabolites
have been reported as important in clinical manifestation of pneumonia.
For the unknown autopsy cases, the sensitivity and specificity were
86 and 84%, respectively. This study successfully investigated the
robustness and usability of post-mortem metabolomics in death investigations.
The identified post-mortem biomarkers correlated well with biomarkers
reported and identified through clinical research.