Postmortem proteomics to discover biomarkers for forensic PMI estimation

Choi, Kyoung-Min; Zissler, Angela; Kim, Eun-Jung; Ehrenfellner, Bianca; Cho, Eunji; Lee, Sein; Steinbacher, Peter; Yun, Ki Na; Shin, Jong Hwan; Kim, Jin Young; Stoiber, Walter; Chung, Heesun; Monticelli, Fabio; Kim, Jae‐Young; Pittner, Stefan

doi:10.1007/s00414-019-02011-6

Cited by 56 publications

(61 citation statements)

References 35 publications

(40 reference statements)

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“…Especially, the loss of the metavinculin band, occurring at day 3 in all animals, confirms the results of previous pilot experiments on pigs and humans [53] and quantitative experiments on rats [54]. Also, the loss of native vinculin and the appearance of degradation products have been reported [53,54]. However, in this particular study, these changes occurred in the later stages of the experimental series in which only a small sample size was available, thus producing large confidence intervals.…”

Section: Discussionsupporting

confidence: 88%

“…Indeed, the present results show the potential of this protein for future application in PMI estimations. Especially, the loss of the metavinculin band, occurring at day 3 in all animals, confirms the results of previous pilot experiments on pigs and humans [53] and quantitative experiments on rats [54]. Also, the loss of native vinculin and the appearance of degradation products have been reported [53,54].…”

Section: Discussionsupporting

confidence: 87%

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A field study to evaluate PMI estimation methods for advanced decomposition stages

et al. 2020

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Estimating the postmortem interval (PMI) is one of the major tasks and a continuous challenge in forensic pathology. It is often an exclusion process of available methods, which ultimately can lead to an unsatisfactory outcome due to poor reliability. This problem is most acute in the late PMI, when decomposition proceeds and some methods (such as rigor, livor, and algor mortis) are no longer applicable. Several methods, such as forensic entomology, skeletal muscle protein degradation, and the study of body decomposition by application of a morphological scoring, are expected to provide further information; however, all have certain limitations and weaknesses. Availability of a toolbox of methods allows a case-specific selection of the most appropriate one(s), or eventually provides improvements in the overall accuracy and precision of the PMI estimation by merging and combining methods. To investigate practical (field) application, eventual interferences, and/or synergetic effects, as well as the robustness of these methods towards specific influencing factors, a field study was conducted, using eight pig cadavers of different body weights and physical coverage, left to decompose under natural conditions for 16 days. Morphological changes during decomposition were assessed using the total body score (TBS), muscle samples were collected to analyze protein degradation, and insect colonization was evaluated. The results reveal strengths and current limitations of all tested methods, as well as promising synergistic effects, and thus, provide a baseline for targeted future research.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 87%

A field study to evaluate PMI estimation methods for advanced decomposition stages

et al. 2020

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“…In a following study, in 2016, Pittner et al [45] analyzed human postmortem skeletal muscle samples, which revealed similar results to previously conducted porcine study, and showed a predictable protein degradation processes in human muscle. Recently a study by Choi et al [46] investigated the ability of usage unbiased protein analysis to find out the postmortem protein changes and detect new possible markers for PMI estimation. They used proteomic profiling of rat and mouse skeletal muscle samples using MS-based proteomic method.…”

Section: Postmortem Intervalmentioning

confidence: 99%

“…Pittner at al. [44] Pittner et al [45] MS-based proteomics Choi et al [46] Handke et al [47] Procopio et al [49] Prieto-Bonete et al [50] Intoxication and abuse of drugs MS-based proteomics Bittencourt et al [51] Diagnosis of disease and cause of death MS-based proteomics Broadbelt at al. [53] Palmiere et al [54] Immunohistochemistry Unkrig et al [55] Mustafa et al [56] Fineschi et al [57] Edston and van Hage-Hamsten [58] Genomics Detection of the biological specimens PCR Nakanishi et al [12] Postmortem interval PCR Pechal et al [19] Intoxication and abuse of drugs PCR Sallaee et al [62] Ikematsu et al…”

Section: Sds-page Western Blotmentioning

confidence: 99%

Omics era in forensic medicine: towards a new age

Akçan¹,

Taştekin²,

Yıldırım³

et al. 2020

Turk J Med Sci

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Introduction The topic "forensic medicine and sciences" is a subdivision of science which is described as the practice of medical/ paramedical scientific knowledge to establish facts in civil and criminal law [1]. Forensic medicine has a multidisciplinary structure in collaboration with other areas such as forensic chemistry, toxicology, biology, psychiatry, and genetics, etc. Since forensic sciences share a common scientific methodology with other science disciplines it is open to collaborate or benefit from novel technologies appeared in any scientific discipline. Therefore, omics emerges as a revolutionary step in forensic sciences and sure carries it towards a new age. The publications regarding omics in various disciplines have become a rising scientific trend worldwide, during the last decade. Furthermore, the number of forensic studies utilizing the methodology of omics has enormously increased in last years. In order to draw attention of forensic and medical professionals, and encourage new studies; the roles and benefits of omics in forensic medicine and sciences are discussed in this review. 2. Omics Omics is a novel multidisciplinary field of various scientific methodologies. Omics defines the collective technologies that measure some characteristics (roles, relationships, and actions) of certain molecules like metabolites, proteins and genes, ending in-omics, as in metabolomics, proteomics, genomics, etc. In past years, omics technologies were applied to diverse fields, because of the ability to assess little changes in a large-scale data with exhaustive metabolite evaluation [2]. With the development of technology, omics-based strategies become cheaper, faster, and very informative, and offer potent alternatives to conventional technics. Furthermore, sample selection has a key role to success in target study. Various human samples can be used for analysis such as blood [3,4], urine [5], hair [6,7], nail [8-10], faeces[11,12], aqueous humour [13] etc. The interactions of omics with each other have been shown in Figure. 2.1. Metabolomics 2.1.1. Definition of metabolomics Metabolomics comprises the studies that are focused on assessment of metabolites and related markers of an Background/aim: Forensic medicine and sciences is a multidisciplinary branch of science, which frequently benefit from novel technologies. State of the art omics technologies have begun to be performed in forensic medicine and sciences, particularly in postmortem interval, intoxication, drugs of abuse, diagnosis of diseases and cause of death. This review aims to discuss the role and use of great omics (metabolomics, proteomics, genomics and transcriptomics) in forensic sciences, in detail. Materials and methods: A detailed review of related literature was performed, and studies were subdivided as per the type of omics. Results and conclusion: Omics seems as a revolutionary step in forensic science and sure carries it towards a new age. The number of forensic studies utilizing omics steadily increases in last years. Omics strategi...

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“…For instance, useful methods for differential diagnosis between freshwater and saltwater drowning have been reported [ 10 , 11 , 12 , 13 , 14 ]. Novel technologies such as proteomics are still in the stage of exploration in forensic pathology [ 15 ], and mainly focused to determine PMI [ 16 , 17 , 18 ]. We proposed to investigate the usefulness of MS-based spectrometry to identify biomarkers that add relevant information in the postmortem diagnosis of drowning and the circumstances of the death.…”

Section: Introductionmentioning

confidence: 99%

Proteomics in Deaths by Drowning: Diagnostic Efficacy of Apolipoprotein A1 and α-1 Antitrypsin, Pilot Study

et al. 2020

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Drowning is one of the leading causes of death worldwide. The pathophysiology of drowning is complex and, sometimes, interpretation of the circumstances of death in the autopsy becomes the main source of information in its diagnosis. New advances in medical research, such as proteomics, especially in forensic pathology, are still in the development. We proposed to investigate the application of Mass Spectrometry-based technologies, to identify differentially expressed proteins that may act as potential biomarkers in the postmortem diagnosis of drowning. We performed a pilot proteomic experiment with the inclusion of two drowned and two control forensic cases. After applying restrictive parameters, we identified apolipoprotein A1 (ApoA1) and α-1 antitrypsin as differentially expressed between the two diagnostic groups. A validation experiment, with the determination of both proteins in 25 forensic cases (16 drowned and 9 controls) was performed, and we corroborated ApoA1 higher values in the drowning group, whereas α-1 antitrypsin showed lower levels. After adjusting by confounder factors, both remained as predictive independent factors for diagnosis of drowning (p = 0.010 and p = 0.022, respectively). We constructed ROC curves for biomarkers’ levels attending at the origin of death and established an ApoA1 cut-off point of 100 mg/dL. Correct classification based on the diagnosis criteria was reached for 73.9% of the cases in a discriminant analysis. We propose apolipoprotein A1 (with our cutoff value for correct classification) and α-1 antitrypsin as valuable biomarkers of drowning. Our study, based on forensic cases, reveals our proteomic approach as a new complementary tool in the forensic diagnosis of drowning and, perhaps, in clinical future implications in drowned patients. However, this is a pilot approach, and future studies are necessary to consolidate our promising preliminary data.

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Postmortem proteomics to discover biomarkers for forensic PMI estimation

Cited by 56 publications

References 35 publications

A field study to evaluate PMI estimation methods for advanced decomposition stages

A field study to evaluate PMI estimation methods for advanced decomposition stages

Omics era in forensic medicine: towards a new age

Proteomics in Deaths by Drowning: Diagnostic Efficacy of Apolipoprotein A1 and α-1 Antitrypsin, Pilot Study

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