Proteomics Goes to Court: A Statistical Foundation for Forensic Toxin/Organism Identification Using Bottom-Up Proteomics

Jarman, Kristin H.; Heller, Natalie C.; Jenson, Sarah C.; Hutchison, Janine R.; Kaiser, Brooke L. Deatherage; Payne, Samuel H.; Wunschel, David S.; Merkley, Eric

doi:10.1021/acs.jproteome.8b00212

Cited by 17 publications

(15 citation statements)

References 59 publications

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“…In other fields of forensic science, such as identification of pathogenic species, sample preparation is generalized to the case of an uncharacterized sample. Taxonomy of the species can be narrowed down or determined using several methods [22,176]. For human-related samples, researchers have to identify which body fluids or tissues exist in the samples [45,149].…”

Section: Challenges Considerations and Future Of Forensic Proteomicsmentioning

confidence: 99%

Proteomics in Forensic Analysis: Applications for Human Samples

et al. 2021

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Proteomics, the large-scale study of all proteins of an organism or system, is a powerful tool for studying biological systems. It can provide a holistic view of the physiological and biochemical states of given samples through identification and quantification of large numbers of peptides and proteins. In forensic science, proteomics can be used as a confirmatory and orthogonal technique for well-built genomic analyses. Proteomics is highly valuable in cases where nucleic acids are absent or degraded, such as hair and bone samples. It can be used to identify body fluids, ethnic group, gender, individual, and estimate post-mortem interval using bone, muscle, and decomposition fluid samples. Compared to genomic analysis, proteomics can provide a better global picture of a sample. It has been used in forensic science for a wide range of sample types and applications. In this review, we briefly introduce proteomic methods, including sample preparation techniques, data acquisition using liquid chromatography-tandem mass spectrometry, and data analysis using database search, spectral library search, and de novo sequencing. We also summarize recent applications in the past decade of proteomics in forensic science with a special focus on human samples, including hair, bone, body fluids, fingernail, muscle, brain, and fingermark, and address the challenges, considerations, and future developments of forensic proteomics.

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Section: Challenges Considerations and Future Of Forensic Proteomicsmentioning

confidence: 99%

Proteomics in Forensic Analysis: Applications for Human Samples

et al. 2021

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“…Formalizing these processes, statistically accounting for multiorganism peptides, closely related proteins, and in particular, empirically validating the output on relevant samples are all requirements for making these approaches ready for routine application. 6,[66][67][68]…”

Section: Forensics and Related Areasmentioning

confidence: 99%

“…However, the specialized requirements for scientific evidence in the legal system require a rigorous statistical basis—the above analysis is merely suggestive, but not conclusive. Formalizing these processes, statistically accounting for multiorganism peptides, closely related proteins, and in particular, empirically validating the output on relevant samples are all requirements for making these approaches ready for routine application 6,66–68 …”

Section: Application Areasmentioning

confidence: 99%

“…Peptides marked with an asterisk have a 100% match to a de novo peptide and are also strong peptides, meaning that their sequences occur sufficiently rarely outside of ricin and related proteins that they can be considered statistically diagnostic of the presence of ricin. 66 Peptides with partial sequence identity could come either from de novo sequencing errors (i.e., imperfectly sequenced ricin peptides) or they could be perfect matches to one of several closely related ricin-like proteins (i.e., perfect matches to a protein that closely resembles ricin). Several ricin-like proteins in castor plant are known, but only ricin and the highly similar agglutinin RCA120 are highly expressed in castor seeds.…”

Section: Complete De Novo Sequencing Of Antibodies and Other Proteinsmentioning

confidence: 99%

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Flying blind, or just flying under the radar? The underappreciated power of de novo methods of mass spectrometric peptide identification

2020

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Mass spectrometry‐based proteomics is a popular and powerful method for precise and highly multiplexed protein identification. The most common method of analyzing untargeted proteomics data is called database searching, where the database is simply a collection of protein sequences from the target organism, derived from genome sequencing. Experimental peptide tandem mass spectra are compared to simplified models of theoretical spectra calculated from the translated genomic sequences. However, in several interesting application areas, such as forensics, archaeology, venomics, and others, a genome sequence may not be available, or the correct genome sequence to use is not known. In these cases, de novo peptide identification can play an important role. De novo methods infer peptide sequence directly from the tandem mass spectrum without reference to a sequence database, usually using graph‐based or machine learning algorithms. In this review, we provide a basic overview of de novo peptide identification methods and applications, briefly covering de novo algorithms and tools, and focusing in more depth on recent applications from venomics, metaproteomics, forensics, and characterization of antibody drugs.

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“…Species identification of morphologically unidentifiable bones or bone fragments can prove challenging in paleontology, anthropology and forensics in the absence of DNA. Numerous methods have been proposed for species identification based on proteins using tandem mass spectrometry (MS) 1 – 3 . Like DNA, these methods rely on detecting genetic changes that occur during speciation.…”

Section: Introductionmentioning

confidence: 99%

A predictive model for vertebrate bone identification from collagen using proteomic mass spectrometry

Yang

Butler

Monier

et al. 2021

Sci Rep

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Proteogenomics is an increasingly common method for species identification as it allows for rapid and inexpensive interrogation of an unknown organism’s proteome—even when the proteome is partially degraded. The proteomic method typically uses tandem mass spectrometry to survey all peptides detectable in a sample that frequently contains hundreds or thousands of proteins. Species identification is based on detection of a small numbers of species-specific peptides. Genetic analysis of proteins by mass spectrometry, however, is a developing field, and the bone proteome, typically consisting of only two proteins, pushes the limits of this technology. Nearly 20% of highly confident spectra from modern human bone samples identify non-human species when searched against a vertebrate database—as would be necessary with a fragment of unknown bone. These non-human peptides are often the result of current limitations in mass spectrometry or algorithm interpretation errors. Consequently, it is difficult to know if a “species-specific” peptide used to identify a sample is actually present in that sample. Here we evaluate the causes of peptide sequence errors and propose an unbiased, probabilistic approach to determine the likelihood that a species is correctly identified from bone without relying on species-specific peptides.

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Proteomics Goes to Court: A Statistical Foundation for Forensic Toxin/Organism Identification Using Bottom-Up Proteomics

Cited by 17 publications

References 59 publications

Proteomics in Forensic Analysis: Applications for Human Samples

Proteomics in Forensic Analysis: Applications for Human Samples

Flying blind, or just flying under the radar? The underappreciated power of de novo methods of mass spectrometric peptide identification

A predictive model for vertebrate bone identification from collagen using proteomic mass spectrometry

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