Ricin-like proteins from the castor plant do not influence liquid chromatography-mass spectrometry detection of ricin in forensically relevant samples

Merkley, Eric; Jenson, Sarah C.; Arce, Jennifer; Melville, Angela M.; Leiser, Owen P.; Wunschel, David S.; Wahl, Karen L.

doi:10.1016/j.toxicon.2017.10.004

Cited by 20 publications

(39 citation statements)

References 49 publications

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“…Ricinus communis agglutinin is a protein that is often isolated as a contaminant of ricin . Eight peptides were identified in the MALDI spectrum as biomarkers of agglutinin in the commercial ricin sample used here (Supplementary Table 1).…”

Section: Resultsmentioning

confidence: 99%

Rapid analysis of ricin using hot acid digestion and MALDI‐TOF mass spectrometry

2018

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Ricin is a protein toxin of considerable interest in forensics. A novel strategy is reported here for rapid detection of ricin based on microwave-assisted hot acid digestion and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. Ricin samples are subjected to aspartate-selective hydrolysis, and biomarker peptide products are characterized by mass spectrometry. Spectra are obtained using post source decay and searched against a protein database. Several advantages are offered by chemical hydrolysis, relative to enzymatic hydrolysis, notably speed, robustness, and the production of heavier biomarkers. Agglutinin contamination is reliably recognized, as is the disulfide bond strongly characteristic of ricin.

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Section: Resultsmentioning

confidence: 99%

Rapid analysis of ricin using hot acid digestion and MALDI‐TOF mass spectrometry

2018

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“…Several ricin-like proteins in castor plant are known, but only ricin and the highly similar agglutinin RCA120 are highly expressed in castor seeds. 68 The high sequence coverage and the high sequence identity both support the presence of ricin or a closely related sequence in the sample; the presence of strong peptides suggests that ricin itself is present. The vertical axis simply lists the detected peptides in sequence order them with pepNovo+.…”

Section: Complete De Novo Sequencing Of Antibodies and Other Proteinsmentioning

confidence: 97%

“…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%

“…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 68 . The high sequence coverage and the high sequence identity both support the presence of ricin or a closely related sequence in the sample; the presence of strong peptides suggests that ricin itself is present.…”

Section: Application Areasmentioning

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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“…In this study, castor seeds from various castor plant cultivars were collected for sample processing. 15 Crude castor seed extracts were prepared from castor seeds via five different methods, designated M0 through M4. Method M0 involves mashing the seed to a semi-uniform consistency.…”

Section: Datasetsmentioning

confidence: 99%

Improving power while controlling the false discovery rate when only a subset of peptides are relevant

Lin

Plubell

Keich

et al. 2020

Preprint

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The standard proteomics database search strategy involves searching spectra against a peptide database and estimating the false discovery rate (FDR) of the resulting set of peptide-spectrum matches. One assumption of this protocol is that all the peptides in the database are relevant to the hypothesis being investigated. However, in settings where researchers are interested in a subset of peptides, alternative search and FDR control strategies are needed. Recently, two methods were proposed to address this problem: subset-search and all-sub. We show that both methods fail to control the FDR. For subset-search, this failure is due to the presence of "neighbor" peptides, which are defined as irrelevant peptides with a similar precursor mass and fragmentation spectrum as a relevant peptide. Not considering neighbors compromises the FDR estimate because a spectrum generated by an irrelevant peptide can incorrectly match well to a relevant peptide. Therefore, we have developed a new method, "filter then subset-neighbor search" (FSNS), that accounts for neighbor peptides. We show evidence that FSNS properly controls the FDR when neighbors are present and that FSNS outperforms group-FDR, the only other method able to control the FDR relative to a subset of relevant peptides.

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Ricin-like proteins from the castor plant do not influence liquid chromatography-mass spectrometry detection of ricin in forensically relevant samples

Cited by 20 publications

References 49 publications

Rapid analysis of ricin using hot acid digestion and MALDI‐TOF mass spectrometry

Rapid analysis of ricin using hot acid digestion and MALDI‐TOF mass spectrometry

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

Improving power while controlling the false discovery rate when only a subset of peptides are relevant

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