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Identification of Single Amino Acid Substitutions in Proteogenomics

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Abstract

An important aim of proteogenomics, which combines data of high throughput nucleic acid and protein analysis, is to reliably identify single amino acid substitutions representing a main type of coding genome variants. Exact knowledge of deviations from the consensus genome can be utilized in several biomedical fields, such as studies of expression of mutated proteins in cancer, deciphering heterozygosity mechanisms, identification of neoantigens in anticancer vaccine production, search for RNA editing sites at the level of the proteome, etc. Generation of this new knowledge requires processing of large data arrays from high–resolution mass spectrometry, where information on single–point protein variation is often difficult to extract. Accordingly, a significant problem in proteogenomic analysis is the presence of high levels of false positive results for variant–containing peptides in the produced results. Here we review recently suggested approaches of high quality proteomics data processing that may provide more reliable identification of single amino acid substitutions, especially contrary to residue modifications occurring in vitro and in vivo. Optimized methods for assessment of false discovery rate save instrumental and computational time spent for validation of interesting findings of amino acid polymorphism by orthogonal methods.

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Abbreviations

ADAR:

adenosine deaminase acting on RNA

DDA:

data–dependent acquisition

DIA:

data–independent acquisition

FDR:

false discovery rate

NGS:

next generation sequencing

SNV:

single nucleotide variant

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Authors and Affiliations

  1. Orekhovich Institute of Biomedical Chemistry, 119121, Moscow, Russia

    S. A. Moshkovskii & K. G. Kuznetsova

  2. Pirogov Russian National Research Medical University, 117997, Moscow, Russia

    S. A. Moshkovskii

  3. Talrose Institute for Energy Problems of Chemical Physics, Russian Academy of Sciences, 119334, Moscow, Russia

    M. V. Ivanov & M. V. Gorshkov

  4. Moscow Institute of Physics and Technology (State University), 141701, Dolgoprudny, Moscow Region, Russia

    M. V. Ivanov & M. V. Gorshkov

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  1. S. A. Moshkovskii
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  2. M. V. Ivanov
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  3. K. G. Kuznetsova
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  4. M. V. Gorshkov
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Correspondence to S. A. Moshkovskii.

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Original Russian Text © S. A. Moshkovskii, M. V. Ivanov, K. G. Kuznetsova, M. V. Gorshkov, 2018, published in Biokhimiya, 2018, Vol. 83, No. 3, pp. 368–378.

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Moshkovskii, S.A., Ivanov, M.V., Kuznetsova, K.G. et al. Identification of Single Amino Acid Substitutions in Proteogenomics. Biochemistry Moscow 83, 250–258 (2018). https://doi.org/10.1134/S0006297918030057

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