Flying Blind, or Just Flying Under the Radar? The Underappreciated Power of De Novo Methods of Mass Spectrometric Peptide Identification

O'Bryon, Isabelle; Jenson, Sarah C.; Merkley, Eric D.

doi:10.1002/pro.3919

Flying Blind, or Just Flying Under the Radar? The Underappreciated Power of De Novo Methods of Mass Spectrometric Peptide Identification

Journal Article · Tue Sep 01 00:00:00 EDT 2020 · Protein Science

DOI:https://doi.org/10.1002/pro.3919· OSTI ID:1668255

O'Bryon, Isabelle ^[1]; ^[1]; ^[1]

BATTELLE (PACIFIC NW LAB)

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 peptide identification infers 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.

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

Sponsoring Organization:: USDOE

DOE Contract Number:: AC05-76RL01830

OSTI ID:: 1668255

Report Number(s):: PNNL-SA-153810

Journal Information:: Protein Science, Journal Name: Protein Science Journal Issue: 9 Vol. 29

Country of Publication:: United States

Language:: English

References (71)

Anatomy and evolution of database search engines—a central component of mass spectrometry based proteomic workflows Verheggen, Kenneth; Ræder, Helge; Berven, Frode S. Mass Spectrometry Reviews, Vol. 39, Issue 3 https://doi.org/10.1002/mas.21543	journal	May 2020
Mass-spectrometric exploration of proteome structure and function Aebersold, Ruedi; Mann, Matthias Nature, Vol. 537, Issue 7620 https://doi.org/10.1038/nature19949	journal	September 2016
Mass spectrometry-based proteomics Aebersold, Ruedi; Mann, Matthias Nature, Vol. 422, Issue 6928 https://doi.org/10.1038/nature01511	journal	March 2003
UVnovo: A de Novo Sequencing Algorithm Using Single Series of Fragment Ions via Chromophore Tagging and 351 nm Ultraviolet Photodissociation Mass Spectrometry Robotham, Scott A.; Horton, Andrew P.; Cannon, Joe R. Analytical Chemistry, Vol. 88, Issue 7 https://doi.org/10.1021/acs.analchem.6b00261	journal	March 2016
Spectral library searching in proteomics Griss, Johannes PROTEOMICS, Vol. 16, Issue 5 https://doi.org/10.1002/pmic.201500296	journal	February 2016
A multi-protease, multi-dissociation, bottom-up-to-top-down proteomic view of the Loxosceles intermedia venom Trevisan-Silva, Dilza; Bednaski, Aline V.; Fischer, Juliana S. G. Scientific Data, Vol. 4, Issue 1 https://doi.org/10.1038/sdata.2017.90	journal	July 2017
Sequencing-Grade De novo Analysis of MS/MS Triplets (CID/HCD/ETD) From Overlapping Peptides Guthals, Adrian; Clauser, Karl R.; Frank, Ari M. Journal of Proteome Research, Vol. 12, Issue 6 https://doi.org/10.1021/pr400173d	journal	May 2013
pNovo+: De Novo Peptide Sequencing Using Complementary HCD and ETD Tandem Mass Spectra Chi, Hao; Chen, Haifeng; He, Kun Journal of Proteome Research, Vol. 12, Issue 2 https://doi.org/10.1021/pr3006843	journal	December 2012
GutenTag: High-Throughput Sequence Tagging via an Empirically Derived Fragmentation Model Tabb, David L.; Saraf, Anita; Yates, John R. Analytical Chemistry, Vol. 75, Issue 23 https://doi.org/10.1021/ac0347462	journal	December 2003
DeNovoGUI: An Open Source Graphical User Interface for de Novo Sequencing of Tandem Mass Spectra Muth, Thilo; Weilnböck, Lisa; Rapp, Erdmann Journal of Proteome Research, Vol. 13, Issue 2 https://doi.org/10.1021/pr4008078	journal	December 2013
Future perspectives of therapeutic monoclonal antibodies Tsumoto, Kanta; Isozaki, Yushi; Yagami, Hisanori Immunotherapy, Vol. 11, Issue 2 https://doi.org/10.2217/imt-2018-0130	journal	February 2019
Proteomics in Forensic Sciences: Identification of the Nature of the Last Meal at Autopsy Pieri, Maria; Lombardi, Antonio; Basilicata, Pascale Journal of Proteome Research, Vol. 17, Issue 7 https://doi.org/10.1021/acs.jproteome.8b00159	journal	May 2018
Challenges and perspectives of metaproteomic data analysis Heyer, Robert; Schallert, Kay; Zoun, Roman Journal of Biotechnology, Vol. 261 https://doi.org/10.1016/j.jbiotec.2017.06.1201	journal	November 2017
Automated Antibody De Novo Sequencing and Its Utility in Biopharmaceutical Discovery Sen, K. Ilker; Tang, Wilfred H.; Nayak, Shruti Journal of The American Society for Mass Spectrometry, Vol. 28, Issue 5 https://doi.org/10.1007/s13361-016-1580-0	journal	January 2017
Protein mass spectrometry detects multiple bloodmeals for enhanced Chagas disease vector ecology Keller, Judith I.; Lima-Cordón, Raquel; Monroy, M. Carlota Infection, Genetics and Evolution, Vol. 74 https://doi.org/10.1016/j.meegid.2019.103998	journal	October 2019
De Novo Peptide Sequencing and Identification with Precision Mass Spectrometry Frank, Ari M.; Savitski, Mikhail M.; Nielsen, Michael L. Journal of Proteome Research, Vol. 6, Issue 1 https://doi.org/10.1021/pr060271u	journal	January 2007
Precision De Novo Peptide Sequencing Using Mirror Proteases of Ac-LysargiNase and Trypsin for Large-scale Proteomics Yang, Hao; Li, Yan-Chang; Zhao, Ming-Zhi Molecular & Cellular Proteomics, Vol. 18, Issue 4 https://doi.org/10.1074/mcp.TIR118.000918	journal	January 2019
Seeing beyond the tip of the iceberg: A deep analysis of the venome of the Brazilian Rattlesnake, Crotalus durissus terrificus Melani, Rafael D.; Araujo, Gabriel D. T.; Carvalho, Paulo C. EuPA Open Proteomics, Vol. 8 https://doi.org/10.1016/j.euprot.2015.05.006	journal	September 2015
Error-Tolerant Identification of Peptides in Sequence Databases by Peptide Sequence Tags Mann, M.; Wilm, M. Analytical Chemistry, Vol. 66, Issue 24 https://doi.org/10.1021/ac00096a002	journal	December 1994
Applications and challenges of forensic proteomics Merkley, Eric D.; Wunschel, David S.; Wahl, Karen L. Forensic Science International, Vol. 297 https://doi.org/10.1016/j.forsciint.2019.01.022	journal	April 2019
Database-independent Protein Sequencing (DiPS) Enables Full-length de Novo Protein and Antibody Sequence Determination Savidor, Alon; Barzilay, Rotem; Elinger, Dalia Molecular & Cellular Proteomics, Vol. 16, Issue 6 https://doi.org/10.1074/mcp.O116.065417	journal	March 2017
Cancer Proteomics and the Elusive Diagnostic Biomarkers Bradshaw, Ralph A.; Hondermarck, Hubert; Rodriguez, Henry PROTEOMICS, Vol. 19, Issue 21-22 https://doi.org/10.1002/pmic.201800445	journal	August 2019
pNovo 3: precise de novo peptide sequencing using a learning-to-rank framework Yang, Hao; Chi, Hao; Zeng, Wen-Feng Bioinformatics, Vol. 35, Issue 14 https://doi.org/10.1093/bioinformatics/btz366	journal	July 2019
An Alignment-Free “Metapeptide” Strategy for Metaproteomic Characterization of Microbiome Samples Using Shotgun Metagenomic Sequencing May, Damon H.; Timmins-Schiffman, Emma; Mikan, Molly P. Journal of Proteome Research, Vol. 15, Issue 8 https://doi.org/10.1021/acs.jproteome.6b00239	journal	July 2016
De novo peptide sequencing by deep learning Tran, Ngoc Hieu; Zhang, Xianglilan; Xin, Lei Proceedings of the National Academy of Sciences, Vol. 114, Issue 31 https://doi.org/10.1073/pnas.1705691114	journal	July 2017
Probabilistic Limit of Detection for Ricin Identification Using a Shotgun Proteomics Assay Heller, Natalie C.; Garrett, Alaine M.; Merkley, Eric D. Analytical Chemistry, Vol. 91, Issue 19 https://doi.org/10.1021/acs.analchem.9b02721	journal	September 2019
Novor: Real-Time Peptide de Novo Sequencing Software Ma, Bin Journal of The American Society for Mass Spectrometry, Vol. 26, Issue 11 https://doi.org/10.1007/s13361-015-1204-0	journal	June 2015
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
Comprehensive de Novo Peptide Sequencing from MS/MS Pairs Generated through Complementary Collision Induced Dissociation and 351 nm Ultraviolet Photodissociation Horton, Andrew P.; Robotham, Scott A.; Cannon, Joe R. Analytical Chemistry, Vol. 89, Issue 6 https://doi.org/10.1021/acs.analchem.7b00130	journal	March 2017
PEAKS: powerful software for peptidede novo sequencing by tandem mass spectrometry Ma, Bin; Zhang, Kaizhong; Hendrie, Christopher Rapid Communications in Mass Spectrometry, Vol. 17, Issue 20 https://doi.org/10.1002/rcm.1196	journal	January 2003
A survey of computational methods and error rate estimation procedures for peptide and protein identification in shotgun proteomics Nesvizhskii, Alexey I. Journal of Proteomics, Vol. 73, Issue 11 https://doi.org/10.1016/j.jprot.2010.08.009	journal	October 2010
Target-Decoy Search Strategy for Mass Spectrometry-Based Proteomics Elias, Joshua E.; Gygi, Steven P. Methods in Molecular Biology https://doi.org/10.1007/978-1-60761-444-9_5	book	December 2009
Charting the Proteomes of Organisms with Unsequenced Genomes by MALDI-Quadrupole Time-of-Flight Mass Spectrometry and BLAST Homology Searching Shevchenko, Andrej; Sunyaev, Shamil; Loboda, Alexander Analytical Chemistry, Vol. 73, Issue 9 https://doi.org/10.1021/ac0013709	journal	May 2001
PepExplorer: A Similarity-driven Tool for Analyzing de Novo Sequencing Results Leprevost, Felipe V.; Valente, Richard H.; Lima, Diogo B. Molecular & Cellular Proteomics, Vol. 13, Issue 9 https://doi.org/10.1074/mcp.M113.037002	journal	May 2014
2018 YPIC Challenge: A Case Study in Characterizing an Unknown Protein Sample Pino, Lindsay; Lin, Andy; Bittremieux, Wout Journal of Proteome Research, Vol. 18, Issue 11 https://doi.org/10.1021/acs.jproteome.9b00384	journal	September 2019
De novo peptide sequencing by tandem MS using complementary CID and electron transfer dissociation Bertsch, Andreas; Leinenbach, Andreas; Pervukhin, Anton ELECTROPHORESIS, Vol. 30, Issue 21 https://doi.org/10.1002/elps.200900332	journal	November 2009
TagGraph reveals vast protein modification landscapes from large tandem mass spectrometry datasets Devabhaktuni, Arun; Lin, Sarah; Zhang, Lichao Nature Biotechnology, Vol. 37, Issue 4 https://doi.org/10.1038/s41587-019-0067-5	journal	April 2019
Automated de novo protein sequencing of monoclonal antibodies Bandeira, Nuno; Pham, Victoria; Pevzner, Pavel Nature Biotechnology, Vol. 26, Issue 12 https://doi.org/10.1038/nbt1208-1336	journal	December 2008
Complete De Novo Assembly of Monoclonal Antibody Sequences Tran, Ngoc Hieu; Rahman, M. Ziaur; He, Lin Scientific Reports, Vol. 6, Issue 1 https://doi.org/10.1038/srep31730	journal	August 2016
A Potential Golden Age to Come-Current Tools, Recent Use Cases, and Future Avenues for De Novo Sequencing in Proteomics Muth, Thilo; Hartkopf, Felix; Vaudel, Marc PROTEOMICS, Vol. 18, Issue 18 https://doi.org/10.1002/pmic.201700150	journal	August 2018
Navigating through metaproteomics data: A logbook of database searching Muth, Thilo; Kolmeder, Carolin A.; Salojärvi, Jarkko PROTEOMICS, Vol. 15, Issue 20 https://doi.org/10.1002/pmic.201400560	journal	April 2015
pDeep: Predicting MS/MS Spectra of Peptides with Deep Learning Zhou, Xie-Xuan; Zeng, Wen-Feng; Chi, Hao Analytical Chemistry, Vol. 89, Issue 23 https://doi.org/10.1021/acs.analchem.7b02566	journal	November 2017
PepNovo: De Novo Peptide Sequencing via Probabilistic Network Modeling Frank, Ari; Pevzner, Pavel Analytical Chemistry, Vol. 77, Issue 4 https://doi.org/10.1021/ac048788h	journal	February 2005
Fragmentation pathways of protonated peptides Paizs, Béla; Suhai, Sándor Mass Spectrometry Reviews, Vol. 24, Issue 4 https://doi.org/10.1002/mas.20024	journal	January 2005
Typing and Characterization of Bacteria Using Bottom-up Tandem Mass Spectrometry Proteomics Boulund, Fredrik; Karlsson, Roger; Gonzales-Siles, Lucia Molecular & Cellular Proteomics, Vol. 16, Issue 6 https://doi.org/10.1074/mcp.M116.061721	journal	April 2017
A Face in the Crowd: Recognizing Peptides Through Database Search Eng, Jimmy K.; Searle, Brian C.; Clauser, Karl R. Molecular & Cellular Proteomics, Vol. 10, Issue 11 https://doi.org/10.1074/mcp.R111.009522	journal	August 2011
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
Evaluating de novo sequencing in proteomics: already an accurate alternative to database-driven peptide identification? Muth, Thilo; Renard, Bernhard Y. Briefings in Bioinformatics, Vol. 19, Issue 5 https://doi.org/10.1093/bib/bbx033	journal	March 2017
De Novo Sequencing and Homology Searching Ma, Bin; Johnson, Richard Molecular & Cellular Proteomics, Vol. 11, Issue 2 https://doi.org/10.1074/mcp.O111.014902	journal	November 2011
Quantitative affinity purification mass spectrometry: a versatile technology to study protein–protein interactions Meyer, Katrina; Selbach, Matthias Frontiers in Genetics, Vol. 6 https://doi.org/10.3389/fgene.2015.00237	journal	July 2015
Lessons in de novo peptide sequencing by tandem mass spectrometry: LESSONS IN DE NOVO PEPTIDE SEQUENCING Medzihradszky, Katalin F.; Chalkley, Robert J. Mass Spectrometry Reviews, Vol. 34, Issue 1 https://doi.org/10.1002/mas.21406	journal	October 2013
Application of de Novo Sequencing to Large-Scale Complex Proteomics Data Sets Devabhaktuni, Arun; Elias, Joshua E. Journal of Proteome Research, Vol. 15, Issue 3 https://doi.org/10.1021/acs.jproteome.5b00861	journal	January 2016
Assessing Protein Sequence Database Suitability Using De Novo Sequencing Johnson, Richard S.; Searle, Brian C.; Nunn, Brook L. Molecular & Cellular Proteomics, Vol. 19, Issue 1 https://doi.org/10.1074/mcp.TIR119.001752	journal	November 2019
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. Journal of Proteome Research, Vol. 17, Issue 9 https://doi.org/10.1021/acs.jproteome.8b00212	journal	July 2018
PEAKS DB: De Novo Sequencing Assisted Database Search for Sensitive and Accurate Peptide Identification Zhang, Jing; Xin, Lei; Shan, Baozhen Molecular & Cellular Proteomics, Vol. 11, Issue 4 https://doi.org/10.1074/mcp.M111.010587	journal	December 2011
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
Semi-supervised learning for peptide identification from shotgun proteomics datasets Käll, Lukas; Canterbury, Jesse D.; Weston, Jason Nature Methods, Vol. 4, Issue 11 https://doi.org/10.1038/nmeth1113	journal	October 2007
High-throughput metaproteomics data analysis with Unipept: A tutorial Mesuere, Bart; Van der Jeugt, Felix; Willems, Toon Journal of Proteomics, Vol. 171 https://doi.org/10.1016/j.jprot.2017.05.022	journal	January 2018
MetaPro-IQ: a universal metaproteomic approach to studying human and mouse gut microbiota Zhang, Xu; Ning, Zhibin; Mayne, Janice Microbiome, Vol. 4, Issue 1 https://doi.org/10.1186/s40168-016-0176-z	journal	June 2016
Multi-Enzymatic Limited Digestion: The Next-Generation Sequencing for Proteomics? Morsa, Denis; Baiwir, Dominique; La Rocca, Raphaël Journal of Proteome Research, Vol. 18, Issue 6 https://doi.org/10.1021/acs.jproteome.9b00044	journal	April 2019
Unipept: Tryptic Peptide-Based Biodiversity Analysis of Metaproteome Samples Mesuere, Bart; Devreese, Bart; Debyser, Griet Journal of Proteome Research, Vol. 11, Issue 12 https://doi.org/10.1021/pr300576s	journal	October 2012
An effective algorithm for peptide de novo sequencing from MS/MS spectra Ma, Bin; Zhang, Kaizhong; Liang, Chengzhi Journal of Computer and System Sciences, Vol. 70, Issue 3 https://doi.org/10.1016/j.jcss.2004.12.001	journal	May 2005
DirecTag: Accurate Sequence Tags from Peptide MS/MS through Statistical Scoring Tabb, David L.; Ma, Ze-Qiang; Martin, Daniel B. Journal of Proteome Research, Vol. 7, Issue 9 https://doi.org/10.1021/pr800154p	journal	September 2008
PeptideMapper: efficient and versatile amino acid sequence and tag mapping Kopczynski, Dominik; Barsnes, Harald; Njølstad, Pål R. Bioinformatics, Vol. 33, Issue 13 https://doi.org/10.1093/bioinformatics/btx122	journal	March 2017
Uncovering Thousands of New Peptides with Sequence-Mask-Search Hybrid De Novo Peptide Sequencing Framework Karunratanakul, Korrawe; Tang, Hsin-Yao; Speicher, David W. Molecular & Cellular Proteomics, Vol. 18, Issue 12 https://doi.org/10.1074/mcp.TIR119.001656	journal	October 2019
Postnovo: Postprocessing Enables Accurate and FDR-Controlled de Novo Peptide Sequencing Miller, Samuel E.; Rizzo, Adriana I.; Waldbauer, Jacob R. Journal of Proteome Research, Vol. 17, Issue 11 https://doi.org/10.1021/acs.jproteome.8b00278	journal	September 2018
A two-step database search method improves sensitivity in peptide sequence matches for metaproteomics and proteogenomics studies Jagtap, Pratik; Goslinga, Jill; Kooren, Joel A. PROTEOMICS, Vol. 13, Issue 8 https://doi.org/10.1002/pmic.201200352	journal	March 2013
Proteomics evidence for kefir dairy in Early Bronze Age China Yang, Yimin; Shevchenko, Anna; Knaust, Andrea Journal of Archaeological Science, Vol. 45 https://doi.org/10.1016/j.jas.2014.02.005	journal	May 2014
De Novo Peptide Sequencing via Tandem Mass Spectrometry Dančík, Vlado; Addona, Theresa A.; Clauser, Karl R. Journal of Computational Biology, Vol. 6, Issue 3-4 https://doi.org/10.1089/106652799318300	journal	October 1999
Mass spectrometry-based proteomics for the forensic identification of vomit traces Pieri, Maria; Silvestre, Angela; De Cicco, Maristella Journal of Proteomics, Vol. 209 https://doi.org/10.1016/j.jprot.2019.103524	journal	October 2019
Ricin-like proteins from the castor plant do not influence liquid chromatography-mass spectrometry detection of ricin in forensically relevant samples Merkley, Eric D.; Jenson, Sarah C.; Arce, Jennifer S. Toxicon, Vol. 140 https://doi.org/10.1016/j.toxicon.2017.10.004	journal	December 2017

Similar Records

Exhaustive Database Searching for Amino Acid Mutations in Proteomes

Journal Article · Sat Dec 31 23:00:00 EST 2011 · Bioinformatics · OSTI ID:1048717

A high-throughput de novo sequencing approach for shotgun proteomics using high-resolution tandem mass spectrometry

Journal Article · Thu Dec 31 23:00:00 EST 2009 · BMC Bioinformatics · OSTI ID:1024242

Related Subjects

proteomics
mass spectrometry
forensics
de novo peptide identification
antibody
venomics

Flying Blind, or Just Flying Under the Radar? The Underappreciated Power of De Novo Methods of Mass Spectrometric Peptide Identification

Citation Formats

References (71)

Similar Records

Related Subjects