Accurate Identification of Deamidation and Citrullination from Global Shotgun Proteomics Data Using a Dual-Search Delta Score Strategy

Wang, Xi; Swensen, Adam C.; Zhang, Tong; Piehowski, Paul D.; Gaffrey, Matthew J.; Monroe, Matthew E.; Zhu, Ying; Dong, Hailiang; Qian, Weijun

doi:10.1021/acs.jproteome.9b00766

Accurate Identification of Deamidation and Citrullination from Global Shotgun Proteomics Data Using a Dual-Search Delta Score Strategy

Journal Article · Mon Mar 16 00:00:00 EDT 2020 · Journal of Proteome Research

DOI:https://doi.org/10.1021/acs.jproteome.9b00766· OSTI ID:1618832

Wang, Xi ^[1]; Swensen, Adam C. ^[2]; Zhang, Tong ^[2]; ^[2]; Gaffrey, Matthew J. ^[2]; ^[2]; ^[2]; ^[3]; ^[2]

Pacific Northwest National Lab. (PNNL), Richland, WA (United States); China Univ. of Geoscience, Beijing (China)
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Miami Univ., Oxford, OH (United States); China Univ. of Geosciences, Beijing (China)

While proteins with deamidated/citrullinated amino acids play critical roles in the pathogenesis of many human diseases, identifying these modifications in complex biological samples has been an ongoing challenge. Herein we present a method to accurately identify these modifications from shotgun proteomics data from a deep proteome profiling study of human pancreatic islets obtained by laser capture microdissection. All MS/MS spectra were searched against database by MSGF+ twice with or without a +0.9840 Da mass shift on amino acids asparagine, glutamine, and arginine (NQR) as a dynamic modification. Consequently, for each spectrum the resulting two peptide-to-spectrum matches (PSM) with their respective MSGF+ scores were used for Delta Score calculation. It was observed that all PSMs with positive Delta Score values were clustered with mass errors around 0 ppm, while PSMs with negative Delta Score values were distributed nearly equally within the defined mass error range (20 ppm) for database searching. To estimate false discovery rate (FDR), a “pseudo-decoy” approach was applied whether datasets were searched against a database with a “real modification” mass shift (+0.9840 Da) and a “mock modification” mass shift (+1.0227 Da). FDR was controlled to ~2% with a Delta Score filter greater than zero. Manual inspection of spectra showed that PSMs with positive Delta Score value contained deamidated/citrullinated fragments in their MS/MS spectra. Finally, the results demonstrated that in-situ deamidated/citrullinated peptides can be accurately identified from shotgun tissue proteomics data by the Dual-search Delta Score Strategy.

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: China Scholarship Council (CSC); National Institutes of Health (NIH); USDOE

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1618832

Report Number(s):: PNNL-SA--149222

Journal Information:: Journal of Proteome Research, Journal Name: Journal of Proteome Research Journal Issue: 4 Vol. 19; ISSN 1535-3893

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

References (39)

Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis Bang, Holger; Egerer, Karl; Gauliard, Anke Arthritis & Rheumatism, Vol. 56, Issue 8 https://doi.org/10.1002/art.22817	journal	January 2007
Data Conversion with ProteoWizard msConvert Adusumilli, Ravali; Mallick, Parag Methods in Molecular Biology https://doi.org/10.1007/978-1-4939-6747-6_23	book	January 2017
An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database Eng, Jimmy K.; McCormack, Ashley L.; Yates, John R. Journal of the American Society for Mass Spectrometry, Vol. 5, Issue 11 https://doi.org/10.1016/1044-0305(94)80016-2	journal	November 1994
Probability-based protein identification by searching sequence databases using mass spectrometry data Perkins, David N.; Pappin, Darryl J. C.; Creasy, David M. Electrophoresis, Vol. 20, Issue 18 https://doi.org/10.1002/(SICI)1522-2683(19991201)20:18<3551::AID-ELPS3551>3.0.CO;2-2	journal	December 1999
Composition of the HLA-DR-associated human thymus peptidome: Antigen processing Collado, Javier A.; Alvarez, Iñaki; Ciudad, M. Teresa European Journal of Immunology, Vol. 43, Issue 9 https://doi.org/10.1002/eji.201243280	journal	July 2013
Recent advances in mass spectrometric analysis of protein deamidation: RECENT ADVANCES IN MASS SPECTROMETRIC ANALYSIS Hao, Piliang; Adav, Sunil S.; Gallart-Palau, Xavier Mass Spectrometry Reviews, Vol. 36, Issue 6 https://doi.org/10.1002/mas.21491	journal	January 2016
Comet: An open-source MS/MS sequence database search tool Eng, Jimmy K.; Jahan, Tahmina A.; Hoopmann, Michael R. PROTEOMICS, Vol. 13, Issue 1 https://doi.org/10.1002/pmic.201200439	journal	December 2012
T Cell Epitopes and Post-Translationally Modified Epitopes in Type 1 Diabetes McGinty, John W.; Marré, Meghan L.; Bajzik, Veronique Current Diabetes Reports, Vol. 15, Issue 11 https://doi.org/10.1007/s11892-015-0657-7	journal	September 2015
Changes in proteins of the human lens in development and aging Dilley, Keith J.; Harding, John J. Biochimica et Biophysica Acta (BBA) - Protein Structure, Vol. 386, Issue 2 https://doi.org/10.1016/0005-2795(75)90283-4	journal	April 1975
Deamidation, isomerization, and racemization at asparaginyl and aspartyl residues in peptides. Succinimide-linked reactions that contribute to protein degradation. Geiger, T.; Clarke, S. Journal of Biological Chemistry, Vol. 262, Issue 2 https://doi.org/10.1016/S0021-9258(19)75855-4	journal	January 1987
Detection and identification of protein citrullination in complex biological systems Clancy, Kathleen W.; Weerapana, Eranthie; Thompson, Paul R. Current Opinion in Chemical Biology, Vol. 30 https://doi.org/10.1016/j.cbpa.2015.10.014	journal	February 2016
A Method for Assessing the Statistical Significance of Mass Spectrometry-Based Protein Identifications Using General Scoring Schemes Fenyö, David; Beavis, Ronald C. Analytical Chemistry, Vol. 75, Issue 4 https://doi.org/10.1021/ac0258709	journal	February 2003
Immunogenic HLA-DR-Presented Self-Peptides Identified Directly from Clinical Samples of Synovial Tissue, Synovial Fluid, or Peripheral Blood in Patients with Rheumatoid Arthritis or Lyme Arthritis Wang, Qi; Drouin, Elise E.; Yao, Chunxiang Journal of Proteome Research, Vol. 16, Issue 1 https://doi.org/10.1021/acs.jproteome.6b00386	journal	November 2016
Asparagine Deamidation: pH-Dependent Mechanism from Density Functional Theory Peters, Baron; Trout, Bernhardt L. Biochemistry, Vol. 45, Issue 16 https://doi.org/10.1021/bi052438n	journal	April 2006
Probability-Based Evaluation of Peptide and Protein Identifications from Tandem Mass Spectrometry and SEQUEST Analysis: The Human Proteome Qian, Wei-Jun; Liu, Tao; Monroe, Matthew E. Journal of Proteome Research, Vol. 4, Issue 1 https://doi.org/10.1021/pr0498638	journal	February 2005
Andromeda: A Peptide Search Engine Integrated into the MaxQuant Environment Cox, Jürgen; Neuhauser, Nadin; Michalski, Annette Journal of Proteome Research, Vol. 10, Issue 4 https://doi.org/10.1021/pr101065j	journal	April 2011
Correction of Errors in Tandem Mass Spectrum Extraction Enhances Phosphopeptide Identification Hao, Piliang; Ren, Yan; Tam, James P. Journal of Proteome Research, Vol. 12, Issue 12 https://doi.org/10.1021/pr4004486	journal	November 2013
Accurate Identification of Deamidated Peptides in Global Proteomics Using a Quadrupole Orbitrap Mass Spectrometer Nepomuceno, Angelito I.; Gibson, Radiance J.; Randall, Shan M. Journal of Proteome Research, Vol. 13, Issue 2 https://doi.org/10.1021/pr400848n	journal	December 2013
Spectral Probabilities and Generating Functions of Tandem Mass Spectra: A Strike against Decoy Databases Kim, Sangtae; Gupta, Nitin; Pevzner, Pavel A. Journal of Proteome Research, Vol. 7, Issue 8 https://doi.org/10.1021/pr8001244	journal	August 2008
A probability-based approach for high-throughput protein phosphorylation analysis and site localization Beausoleil, Sean A.; Villén, Judit; Gerber, Scott A. Nature Biotechnology, Vol. 24, Issue 10 https://doi.org/10.1038/nbt1240	journal	September 2006
MS-GF+ makes progress towards a universal database search tool for proteomics Kim, Sangtae; Pevzner, Pavel A. Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms6277	journal	October 2014
Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry Elias, Joshua E.; Gygi, Steven P. Nature Methods, Vol. 4, Issue 3 https://doi.org/10.1038/nmeth1019	journal	February 2007
Nanowell-mediated two-dimensional liquid chromatography enables deep proteome profiling of <1000 mammalian cells Dou, Maowei; Zhu, Ying; Liyu, Andrey Chemical Science, Vol. 9, Issue 34 https://doi.org/10.1039/C8SC02680G	journal	January 2018
Deamidation of human proteins Robinson, N. E.; Robinson, A. B. Proceedings of the National Academy of Sciences, Vol. 98, Issue 22 https://doi.org/10.1073/pnas.221463198	journal	October 2001
Controlled Deamidation of Peptides and Proteins: An Experimental Hazard and a Possible Biological Timer Robinson, A. B.; McKerrow, J. H.; Cary, P. Proceedings of the National Academy of Sciences, Vol. 66, Issue 3 https://doi.org/10.1073/pnas.66.3.753	journal	July 1970
Detection, Evaluation and Minimization of Nonenzymatic Deamidation in Proteomic Sample Preparation Hao, Piliang; Ren, Yan; Alpert, Andrew J. Molecular & Cellular Proteomics, Vol. 10, Issue 10 https://doi.org/10.1074/mcp.O111.009381	journal	October 2011
Mining the Human Tissue Proteome for Protein Citrullination Lee, Chien-Yun; Wang, Dongxue; Wilhelm, Mathias Molecular & Cellular Proteomics, Vol. 17, Issue 7 https://doi.org/10.1074/mcp.RA118.000696	journal	July 2018
ProteoWizard: open source software for rapid proteomics tools development Kessner, Darren; Chambers, Matt; Burke, Robert Bioinformatics, Vol. 24, Issue 21 https://doi.org/10.1093/bioinformatics/btn323	journal	July 2008
T cell recognition of a highly conserved epitope in heat shock protein 60: self-tolerance maintained by TCR distinguishing between asparagine and aspartic acid Lillicrap, M. S. International Immunology, Vol. 16, Issue 3 https://doi.org/10.1093/intimm/dxh032	journal	March 2004
Antigen Targets of Type 1 Diabetes Autoimmunity Roep, B. O.; Peakman, M. Cold Spring Harbor Perspectives in Medicine, Vol. 2, Issue 4 https://doi.org/10.1101/cshperspect.a007781	journal	January 2012
Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. Schellekens, G. A.; de Jong, B. A.; van den Hoogen, F. H. Journal of Clinical Investigation, Vol. 101, Issue 1 https://doi.org/10.1172/JCI1316	journal	January 1998
Deamidation of human erythrocyte protein 4.1: possible role in aging Inaba, M.; Gupta, Kc; Kuwabara, M. Blood, Vol. 79, Issue 12 https://doi.org/10.1182/blood.V79.12.3355.3355	journal	June 1992
Dementia-linked amyloidosis is associated with brain protein deamidation as revealed by proteomic profiling of human brain tissues Adav, Sunil S.; Gallart-Palau, Xavier; Tan, Kok Hian Molecular Brain, Vol. 9, Issue 1 https://doi.org/10.1186/s13041-016-0200-z	journal	February 2016
Citrullinated Glucose-Regulated Protein 78 Is an Autoantigen in Type 1 Diabetes Rondas, Dieter; Crèvecoeur, Inne; D’Hertog, Wannes Diabetes, Vol. 64, Issue 2 https://doi.org/10.2337/db14-0621	journal	September 2014
Nonenzymatic Deamidation of Asparaginyl and Glutaminyl Residues in Protein Tonie Wright, H.; Urry, Dan W. Critical Reviews in Biochemistry and Molecular Biology, Vol. 26, Issue 1 https://doi.org/10.3109/10409239109081719	journal	January 1991
Cutting Edge: Selective Deamidation by Tissue Transglutaminase Strongly Enhances Gliadin-Specific T Cell Reactivity van de Wal, Yvonne; Kooy, Yvonne; van Veelen, Peter The Journal of Immunology, Vol. 161, Issue 4 https://doi.org/10.4049/jimmunol.161.4.1585	journal	August 1998
Islet-Specific Glucose-6-Phosphatase Catalytic Subunit-Related Protein-Reactive CD4 ⁺ T Cells in Human Subjects Yang, Junbao; Danke, Nancy A.; Berger, DeAnna The Journal of Immunology, Vol. 176, Issue 5 https://doi.org/10.4049/jimmunol.176.5.2781	journal	February 2006
Optimizing the Identification of Citrullinated Peptides by Mass Spectrometry: Utilizing the Inability of Trypsin to Cleave after Citrullinated Amino Acids Bennike, Tue; Lauridsen, Kasper B.; Olesen, Michael Kruse Journal of Proteomics & Bioinformatics, Vol. 6, Issue 12 https://doi.org/10.4172/jpb.1000293	journal	January 2013
Dementia-linked amyloidosis is associated with brain protein deamidation as revealed by proteomic profiling of human brain tissues Adav, Sunil; Gallart-Palau, Xavier; Tan, Kok Figshare https://doi.org/10.6084/m9.figshare.c.3618860	collection	January 2016

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Accurate Identification of Deamidation and Citrullination from Global Shotgun Proteomics Data Using a Dual-Search Delta Score Strategy

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