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.

Keywords: degradation; postmortem interval; protein; time since death.

Figure 1

Flow chart of the literature search process and study selection according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. To generate Boolean operators for searches in PubMed (P) and Ovid (O), the following phrases were combined with “AND (postmortem OR post mortem OR post-mortem) AND (protein degradation OR protein decomposition)”. 1: “(myocard OR heart OR muscle)”, 2. “(lung OR pulmonary OR respiratory)”, 3. “(brain OR neural)”, 4. “(kidney OR nephrotic)”, 5. “(liver OR hepatic)”, 6. “(pancreas OR pancreatic)”, 7. “(spleen)”, 8. “(skin OR dermal)”, 9. “(bone OR skeletal OR skeleton)”, 10. “(cartilage OR chondral)”, 11. “(teeth OR pulp)”.

Figure 2

Frequency diagrams of analyzed species (a), methods (b), tissues (c), and proteins (d) targeted in at least two studies. All investigated proteins are listed in Table S1.

Figure 3

Risk of bias assessment of included studies. Green = low risk of bias, yellow = moderate risk of bias, red = high risk of bias. Mixed colors indicate that parts of the study were assessed with different risks of bias.

Figure 4

Timeline of published studies. The first included study aiming to determine time since death by means of protein degradation analysis was published in 1999. At around 2015, the number of published articles in this field increased significantly and remained on an elevated level up to present.

Figure 5

Overview of the body of evidence. Evidence base, consistency and level of evidence are depicted for methods (a), tissues (b), and proteins (c). Studies with low risk of bias are marked in green, those with moderate risk of bias in orange, and those with high risk of bias studies in red. Numbers indicate the amount of corresponding studies. Evidence levels: level I, quantitative studies on human tissue; level II, quantitative animal or human case studies; level III, animal case studies; n.a.: no level applicable (grey) (only referring to studies in review article [25]).

Figure 6

Summary of postmortem degradation events of proteins in various tissues over investigated PMI in logarithmic scale, demonstrating the applicability of tissues and proteins in respective postmortem time frames. The figure includes all proteins originating from studies assigned with a low and moderate risk of bias. Temporal references (day, week, month, year, >year) are indicated by different background colors.

Figure 6

Summary of postmortem degradation events of proteins in various tissues over investigated PMI in logarithmic scale, demonstrating the applicability of tissues and proteins in respective postmortem time frames. The figure includes all proteins originating from studies assigned with a low and moderate risk of bias. Temporal references (day, week, month, year, >year) are indicated by different background colors.