Postmortem Protein Degradation as a Tool to Estimate the PMI: A Systematic Review

Abstract

Objectives: We provide a systematic review of the literature to evaluate the current research status of protein degradation-based postmortem interval (PMI) estimation. Special attention is paid to the applicability of the proposed approaches/methods in forensic routine practice. Method: A systematic review of the literature on protein degradation in tissues and organs of animals and humans was conducted. Therefore, we searched the scientific databases Pubmed and Ovid for publications until December 2019. Additional searches were performed in Google Scholar and the reference lists of eligible articles. Results: A total of 36 studies were included. This enabled us to consider the degradation pattern of over 130 proteins from 11 different tissues, studied with different methods including well-established and modern approaches. Although comparison between studies is complicated by the heterogeneity of study designs, tissue types, methods, proteins and outcome measurement, there is clear evidence for a high explanatory power of protein degradation analysis in forensic PMI analysis. Conclusions: Although only few approaches have yet exceeded a basic research level, the current research status provides strong evidence in favor of the applicability of a protein degradation-based PMI estimation method in routine forensic practice. Further targeted research effort towards specific aims (also addressing influencing factors and exclusion criteria), especially in human tissue will be required to obtain a robust, reliable laboratory protocol, and collect sufficient data to develop accurate multifactorial mathematical decomposition models.

Dismembered porcine limbs as a proxy for postmortem muscle protein degradation

“…Furthermore, the time-dependent decrease and loss of the native proteins were, in parts, accompanied by the formation of split products with a high consistency at distinct time points postmortem. Thus, again, the analysis of the degradation patterns of skeletal muscle proteins is confirmed to be a very promising approach for PMI delimitation in the first 10 days post mortem [see review of Zissler et al 2020] [ 27 ]. However, it should be noted that also proteins of other tissues have potential to aid in PMI delimitation, from very early [ 28 , 29 ] to late PMI phases [ 30 , 31 ].…”

Influencing Factors on Postmortem Protein Degradation for PMI Estimation: A Systematic Review

“…These findings have been repeatedly confirmed in other research fields (e.g., meat science [ 27 , 28 , 29 ]). However, to establish corrective factors that are applicable to temperature effects on protein degradation in routine cases inevitably requires further human decomposition studies, particularly because the temporal patterns of body cooling highly likely diverge between species [ 15 ]. Admittedly, it is comparatively easy to test temperature effects on protein degradation dynamics in animal models under standardized laboratory conditions, but extremely challenging to do the same in human tissues, for which exact temperature profiles between death and autopsy (sampling) are often unavailable.…”

“…A preselection of studies was conducted electronically based on the following predefined inclusion criteria: “peer revision”, “English language”, “availability of full text” and “publishing date between 2000 and 2020”. The timeframe was selected based on a previous study [ 15 ], a systematic review article on protein decomposition-based research in the forensic context, in which it was shown that the earliest relevant research originated in 1999.…”

“…The risk of bias of individual studies was assessed using a previously published framework ([ 15 ]), which we also deemed appropriate for use in the present review ( File S1, File S2 ). Based on the Cochrane Risk of Bias tool RoB 2.0 [ 17 ], this established matrix involves specific signaling questions summarized in six domains, including general study design, precision in reporting, presence of outcome data, outcome measurements, selective outcome reporting, and the multiple use of data.…”

“…Several proposed approaches for PMI estimation therefore remain in their early stages of development, and only rarely a has method progressed beyond the pilot stage and is actually involved in forensic casework such as the analysis of protein decomposition [ 13 ]. As outlined above, the recently demonstrated predictability of degradation patterns of proteins [ 14 , 15 , 16 ] is limited by effects of various influences [ 12 ]. A key to improve the method is to obtain a deeper understanding of the effects of intrinsic and extrinsic factors, enabling the specification of suitable correction factors and/or exclusion criteria that, in turn, enhance their reliability and applicability.…”