Dataset Information

Forensic proteomics to identify an unknown snake venom in blood

ABSTRACT: Although forensic proteomics is an emerging field, it remains underutilized as a tool for criminal investigations. Here we present its use in providing key evidence in an involuntary manslaughter case. The defendant was known to be a keeper of exotic snakes, including several venomous species, which led to a probe of potential snake venom components in the blood of the deceased. One major challenge of the investigation was the overwhelming presence of several blood proteins, such as albumin and immunoglobulins, which obscures the detection of less abundant ones. To mitigate this problem, proteins from the blood were processed in four different ways involving a combination of immunodepletion and fractionation methods, then prepared for peptide identification by mass spectrometry. We were able to sequence ~15,000 peptides, but another challenge was to differentiate between human and snake proteins, given the genetic similarities that are shared by the two species. After a thorough bioinformatics search and manual inspection, we found that <1% of the sequenced peptides were matched unequivocally to snake proteins, including a well-known venom component, phospholipase A2. This led to a court-issued search warrant of the defendant’s home, followed by his arrest and an eventual guilty plea with formal sentencing to 18 months in prison. The work outlined here is an example of proteomics technology that can help to expand the scope of forensic genetics.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Serpentes

TISSUE(S): Blood

SUBMITTER: Queenie Chan

LAB HEAD: Leonard James Foster

PROVIDER: PXD020203 | Pride | 2022-01-24

REPOSITORIES: Pride

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The application of forensic proteomics to identify an unknown snake venom in a deceased toddler.

Chan Queenie W T QWT Rogalski Jason J Moon Kyung-Mee KM Foster Leonard J LJ

Forensic science international 20210504

Proteomics is the global analysis of proteins in a sample, and its methodologies are commonly applied in life science research. Despite its wide applicability however, proteomics is rarely used as a tool in criminal investigations. Here we present a case where the technique provided key evidence in a case that involved the death of a two-year old girl. The defendant was known to keep exotic snakes, including several venomous species, which led the coroner to probe whether there could be snake ve ...[more]

PMID: 33984813

Similar Datasets

Project description:The Mojave rattlesnake (Crotalus scutulatus scutulatus) is classified as the “highest medically important” snake in the risk categories in the United States. Although responsible for fewer snakebite envenomations and deaths compared to other species, Mojave rattlesnake venom is poorly characterized and shows significant geographical variability. The venom of Type A animals primarily contains the β-neurotoxin referred to as Mojave Toxin (MTX), which is responsible for the neurotoxic effects that make bites from this snake particularly feared. Previous studies have shown that β-neurotoxin from different snake species produced similar but complex effects by mechanisms that are not fully understood. We performed a genome-wide transcriptomic analysis of the neurocellular response to Mojave Type A rattlesnake venom using induced pluripotent stem cell (iPSC) -derived human neural stem cells (NSCs) to unveil the molecular mechanisms underlying the damage caused by this snake’s envenomation. Our results suggest that snake venom metalloproteases (svMPs), although have a limited repertoire in type A animal venom, facilitate venom spread by digesting tissue's extracellular matrix. The MTX, which is composed of heterodimers of basic and acidic phospholipase A2 (PLA2) and is the dominant constituent of this venom, co-opts the host arachidonic acid and Ca2+ second messenger mechanisms in a dose- and time-dependent escalating venom damage. The release of arachidonic acid and the rapid increase in intracellular Ca2+ caused by the PLA2 activity of MTX triggers multiple signaling cascades. The activation of MAPKs and NF-κB regulated proinflammatory cascades were the top enriched pathways in the shorter 4-hour NSC response to venom challenge and suggest a significant role of PKC-δ in the activation of MAPKs. The rapid increase in intercellular Ca2+ and resulting cellular depolarization plausibly have a role in neurotransmitter overload in the cholinergic and glutamatergic excitatory synapses and MTX-induced presynaptic blockade of nerve signals. The expression of the acetylcholinesterase gene (ACHE), which degrades acetylcholine, and the downregulation of GRIK1 and GRIK3 genes, which encode KA-iGluRs proteins suggest a cellular response to neurotransmitter overload in the excitatory synapses. Our results also show that the MTX/svPLA2 mediated dysregulation of Ca2+ homeostasis, particularly depletion from the endoplasmic reticulum (ER), causes ER stress and upregulation of unfolded protein response (UPR). The UPR and the oxidative stress caused by ROS generated in CYP1A1-mediated hydroxylation of arachidonic acid, contribute to mitochondrial membrane permeabilization. The activation of UPR, mitochondrial toxicity, and oxidative stress, constitute the degenerative phase of the venom challenge in NSCs and synergistically contribute to apoptotic and ferroptotic programmed cell death.

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