{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T18:17:16Z","timestamp":1783102636478,"version":"3.54.6"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T00:00:00Z","timestamp":1707523200000},"content-version":"vor","delay-in-days":19,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Chinese Ministry of Technology to Peng Cheng Laboratory"},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFA1301603"],"award-info":[{"award-number":["2021YFA1301603"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFE0202200"],"award-info":[{"award-number":["2020YFE0202200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research and Development Program of Guangzhou Laboratory","award":["SRPG22-001"],"award-info":[{"award-number":["SRPG22-001"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32088101"],"award-info":[{"award-number":["32088101"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2019-I2M-5-063"],"award-info":[{"award-number":["2019-I2M-5-063"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>De novo peptide sequencing is a promising approach for novel peptide discovery, highlighting the performance improvements for the state-of-the-art models. The quality of mass spectra often varies due to unexpected missing of certain ions, presenting a significant challenge in de novo peptide sequencing. Here, we use a novel concept of complementary spectra to enhance ion information of the experimental spectrum and demonstrate it through conceptual and practical analyses. Afterward, we design suitable encoders to encode the experimental spectrum and the corresponding complementary spectrum and propose a de novo sequencing model $\\pi$-HelixNovo based on the Transformer architecture. We first demonstrated that $\\pi$-HelixNovo outperforms other state-of-the-art models using a series of comparative experiments. Then, we utilized $\\pi$-HelixNovo to de novo gut metaproteome peptides for the first time. The results show $\\pi$-HelixNovo increases the identification coverage and accuracy of gut metaproteome and enhances the taxonomic resolution of gut metaproteome. We finally trained a powerful $\\pi$-HelixNovo utilizing a larger training dataset, and as expected, $\\pi$-HelixNovo achieves unprecedented performance, even for peptide-spectrum matches with never-before-seen peptide sequences. We also use the powerful $\\pi$-HelixNovo to identify antibody peptides and multi-enzyme cleavage peptides, and $\\pi$-HelixNovo is highly robust in these applications. Our results demonstrate the effectivity of the complementary spectrum and take a significant step forward in de novo peptide sequencing.<\/jats:p>","DOI":"10.1093\/bib\/bbae021","type":"journal-article","created":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T14:00:53Z","timestamp":1707573653000},"source":"Crossref","is-referenced-by-count":35,"title":["Introducing \u03c0-HelixNovo for practical large-scale de novo peptide sequencing"],"prefix":"10.1093","volume":"25","author":[{"given":"Tingpeng","family":"Yang","sequence":"first","affiliation":[{"name":"Peng Cheng Laboratory , Shenzhen, 518055 , China"},{"name":"Tsinghua Shenzhen International Graduate School , Shenzhen, 518055 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianze","family":"Ling","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Proteomics , Beijing Proteome Research Center, , Beijing, 102206 , China"},{"name":"National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics , Beijing Proteome Research Center, , Beijing, 102206 , China"},{"name":"School of Life Sciences, Tsinghua University , Beijing 100084 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyan","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Proteomics , Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), , Beijing, 102206 , China"},{"name":"Beijing Institute of Lifeomics , Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), , Beijing, 102206 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhendong","family":"Liang","sequence":"additional","affiliation":[{"name":"Peng Cheng Laboratory , Shenzhen, 518055 , China"},{"name":"Tsinghua Shenzhen International Graduate School , Shenzhen, 518055 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Xu","sequence":"additional","affiliation":[{"name":"Peng Cheng Laboratory , Shenzhen, 518055 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiansong","family":"Huang","sequence":"additional","affiliation":[{"name":"Peng Cheng Laboratory , Shenzhen, 518055 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linhai","family":"Xie","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Proteomics , Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), , Beijing, 102206 , China"},{"name":"Beijing Institute of Lifeomics , Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), , Beijing, 102206 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghong","family":"He","sequence":"additional","affiliation":[{"name":"Peng Cheng Laboratory , Shenzhen, 518055 , China"},{"name":"Tsinghua Shenzhen International Graduate School , Shenzhen, 518055 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leyuan","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Proteomics , Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), , Beijing, 102206 , China"},{"name":"Beijing Institute of Lifeomics , Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), , Beijing, 102206 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuchu","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Proteomics , Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), , Beijing, 102206 , China"},{"name":"Beijing Institute of Lifeomics , Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), , Beijing, 102206 , China"},{"name":"Research Unit of Proteomics Driven Cancer Precision Medicine, Chinese Academy of Medical Sciences , Beijing 102206 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Peng Cheng Laboratory , Shenzhen, 518055 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Chang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Proteomics , Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), , Beijing, 102206 , China"},{"name":"Beijing Institute of Lifeomics , Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), , Beijing, 102206 , China"},{"name":"Research Unit of Proteomics Driven Cancer Precision Medicine, Chinese Academy of Medical Sciences , Beijing 102206 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,2,10]]},"reference":[{"issue":"10","key":"2024040614453657600_ref1","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/S0167-7799(97)01110-4","article-title":"Emerging tandem-mass-spectrometry techniques for the rapid identification of proteins","volume":"15","author":"Dongr\u00e9","year":"1997","journal-title":"Trends Biotechnol"},{"issue":"4","key":"2024040614453657600_ref2","doi-asserted-by":"crossref","first-page":"519","DOI":"10.2144\/05384TE01","article-title":"Tandem mass spectrometry for peptide and protein sequence analysis","volume":"38","author":"Coon","year":"2005","journal-title":"Biotechniques"},{"issue":"17","key":"2024040614453657600_ref3","doi-asserted-by":"crossref","first-page":"6233","DOI":"10.1073\/pnas.83.17.6233","article-title":"Protein sequencing by tandem mass spectrometry","volume":"83","author":"Hunt","year":"1986","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"22","key":"2024040614453657600_ref4","doi-asserted-by":"crossref","first-page":"11361","DOI":"10.1021\/acs.analchem.5b02721","article-title":"Extracting accurate precursor information for tandem mass spectra by RawConverter","volume":"87","author":"He","year":"2015","journal-title":"Anal Chem"},{"issue":"11","key":"2024040614453657600_ref5","doi-asserted-by":"crossref","first-page":"R111.009522","DOI":"10.1074\/mcp.R111.009522","article-title":"A face in the crowd: recognizing peptides through database search","volume":"10","author":"Eng","year":"2011","journal-title":"Mol Cell Proteomics"},{"issue":"9","key":"2024040614453657600_ref6","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1074\/mcp.M800122-MCP200","article-title":"Generalized method for probability-based peptide and protein identification from tandem mass spectrometry data and sequence database searching","volume":"7","author":"Ramos-Fernandez","year":"2008","journal-title":"Mol Cell Proteomics"},{"issue":"8","key":"2024040614453657600_ref7","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1021\/ac00104a020","article-title":"Method to correlate tandem mass spectra of modified peptides to amino acid sequences in the protein database","volume":"67","author":"Yates","year":"1995","journal-title":"Anal Chem"},{"issue":"4","key":"2024040614453657600_ref8","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1002\/pmic.200900459","article-title":"De novo sequencing of peptides by Ms\/Ms","volume":"10","author":"Seidler","year":"2010","journal-title":"Proteomics"},{"issue":"20","key":"2024040614453657600_ref9","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1002\/rcm.1196","article-title":"Peaks: powerful software for Peptidede novo sequencing by tandem mass spectrometry","volume":"17","author":"Ma","year":"2003","journal-title":"Rapid Commun Mass Spectrom"},{"issue":"7","key":"2024040614453657600_ref10","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/nbt0704-909","article-title":"What is dynamic programming?","volume":"22","author":"Eddy","year":"2004","journal-title":"Nat Biotechnol"},{"key":"2024040614453657600_ref11","first-page":"3104","volume-title":"Advances in Neural Information Processing Systems 27: 28th Annual Conference on Neural Information Processing Systems 2014 [(NIPS)]","author":"Sutskever","year":"2014"},{"issue":"31","key":"2024040614453657600_ref12","doi-asserted-by":"crossref","first-page":"8247","DOI":"10.1073\/pnas.1705691114","article-title":"De novo peptide sequencing by deep learning","volume":"114","author":"Tran","year":"2017","journal-title":"Proc Natl Acad Sci"},{"key":"2024040614453657600_ref13","volume-title":"2017 International Conference on Engineering and Technology (ICET)","author":"Albawi","year":"2017"},{"issue":"7","key":"2024040614453657600_ref14","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1162\/neco_a_01199","article-title":"A review of recurrent neural networks: Lstm cells and network architectures","volume":"31","author":"Yu","year":"2019","journal-title":"Neural Comput"},{"issue":"5","key":"2024040614453657600_ref15","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1021\/pr100182k","article-title":"pNovo: De novo peptide sequencing and identification using Hcd spectra","volume":"9","author":"Chi","year":"2010","journal-title":"J Proteome Res"},{"issue":"5","key":"2024040614453657600_ref16","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/s42256-021-00304-3","article-title":"Computationally instrument-resolution-independent De novo peptide sequencing for high-resolution devices. Nature","volume":"3","author":"Qiao","year":"2021","journal-title":"Mach Intell"},{"key":"2024040614453657600_ref17","first-page":"25514","volume-title":"Proceedings of Machine Learning Research: Proceedings of the 39th International Conference on Machine Learning","author":"Yilmaz","year":"2022"},{"key":"2024040614453657600_ref18","article-title":"Attention is all you need","volume":"30","author":"Vaswani","year":"2017","journal-title":"Adv Neural Inform Process Systems"},{"key":"2024040614453657600_ref19","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/S0076-6879(05)02005-7","article-title":"Collision-induced dissociation (CID) of peptides and proteins","volume":"402","author":"Wells","year":"2005","journal-title":"Methods Enzymol"},{"issue":"9","key":"2024040614453657600_ref20","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/nmeth1060","article-title":"Higher-energy C-trap dissociation for peptide modification analysis","volume":"4","author":"Olsen","year":"2007","journal-title":"Nat Methods"},{"issue":"9","key":"2024040614453657600_ref21","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1021\/ac026359i","article-title":"Cleavage N-terminal to proline: analysis of a database of peptide tandem mass spectra","volume":"75","author":"Breci","year":"2003","journal-title":"Anal Chem"},{"key":"2024040614453657600_ref22","volume-title":"Advances in Neural Information Processing Systems Datasets and Benchmarks Track: 36th Conference on Neural Information Processing Systems (NeurIPS 2022)","author":"Shouman","year":"2022"},{"issue":"12","key":"2024040614453657600_ref23","doi-asserted-by":"crossref","first-page":"R111.008565","DOI":"10.1074\/mcp.R111.008565","article-title":"Building and searching tandem mass spectral libraries for peptide identification","volume":"10","author":"Lam","year":"2011","journal-title":"Mol Cell Proteomics"},{"issue":"5","key":"2024040614453657600_ref24","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1021\/ac026122m","article-title":"Statistical characterization of ion trap tandem mass spectra from doubly charged tryptic peptides","volume":"75","author":"Tabb","year":"2003","journal-title":"Anal Chem"},{"issue":"7","key":"2024040614453657600_ref25","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/j.jasms.2006.02.003","article-title":"Determination of peptide and protein ion charge states by Fourier transformation of isotope-resolved mass spectra","volume":"17","author":"Tabb","year":"2006","journal-title":"J Am Soc Mass Spectrom"},{"issue":"1","key":"2024040614453657600_ref26","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.cell.2019.08.011","article-title":"Interspecies competition impacts targeted manipulation of human gut bacteria by fiber-derived glycans","volume":"179","author":"Patnode","year":"2019","journal-title":"Cell"},{"issue":"4","key":"2024040614453657600_ref27","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.cels.2018.08.004","article-title":"Assembling the community-scale discoverable human proteome","volume":"7","author":"Wang","year":"2018","journal-title":"Cell Systems"},{"issue":"1","key":"2024040614453657600_ref28","doi-asserted-by":"crossref","first-page":"bbac542","DOI":"10.1093\/bib\/bbac542","article-title":"Comprehensive evaluation of peptide de novo sequencing tools for monoclonal antibody assembly","volume":"24","author":"Beslic","year":"2023","journal-title":"Brief Bioinform"},{"issue":"6","key":"2024040614453657600_ref29","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.cels.2017.05.009","article-title":"An optimized shotgun strategy for the rapid generation of comprehensive human proteomes","volume":"4","author":"Bekker-Jensen","year":"2017","journal-title":"Cell Syst"},{"key":"2024040614453657600_ref30","volume-title":"1st International Conference on Learning Representations: Workshop Track Proceedings","author":"Mikolov","year":"2013"},{"issue":"3","key":"2024040614453657600_ref31","first-page":"507","article-title":"Optimal structure identification with greedy search","volume":"3","author":"Chickering","year":"2003","journal-title":"J Mach Learn Res"},{"issue":"1","key":"2024040614453657600_ref32","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s10994-013-5371-6","article-title":"Beam search algorithms for multilabel learning","volume":"92","author":"Kumar","year":"2013","journal-title":"Mach Learn"},{"key":"2024040614453657600_ref33","doi-asserted-by":"crossref","first-page":"6239","DOI":"10.1109\/TIP.2022.3208437","article-title":"Beyond greedy search: tracking by multi-agent reinforcement learning-based beam search","volume":"31","author":"Wang","year":"2022","journal-title":"IEEE Trans Image Process"},{"key":"2024040614453657600_ref34","doi-asserted-by":"crossref","DOI":"10.18653\/v1\/2020.emnlp-main.170","article-title":"If beam search is the answer, what was the question?","volume-title":"Association for Computational Linguistics: Proceedings of the 2020 Conference on Empirical Methods in Natural Language Processing (EMNLP)","author":"Meister","year":"2020"},{"issue":"1","key":"2024040614453657600_ref35","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s10479-005-5724-z","article-title":"A tutorial on the cross-entropy method","volume":"134","author":"Boer","year":"2005","journal-title":"Ann Operat Res"},{"issue":"3","key":"2024040614453657600_ref36","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nmeth1019","article-title":"Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry","volume":"4","author":"Elias","year":"2007","journal-title":"Nat Methods"},{"issue":"12","key":"2024040614453657600_ref37","doi-asserted-by":"crossref","first-page":"5773","DOI":"10.1021\/pr300576s","article-title":"Unipept: tryptic peptide-based biodiversity analysis of Metaproteome samples","volume":"11","author":"Mesuere","year":"2012","journal-title":"J Proteome Res"},{"key":"2024040614453657600_ref38","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/nbt1408","article-title":"Proteome-derived, database-searchable peptide libraries for identifying protease cleavage sites","volume":"26","author":"Schilling","year":"2008","journal-title":"Nat Biotechnol"},{"issue":"1","key":"2024040614453657600_ref39","first-page":"11","article-title":"Complementary ion Spectrum strategy for improving the sensitivity of open search","volume":"41","author":"Jia-wei","year":"2020","journal-title":"J Chinese Mass Spectrometr Soc"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/25\/2\/bbae021\/57169420\/bbae021.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/25\/2\/bbae021\/57169420\/bbae021.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,6]],"date-time":"2024-04-06T14:59:02Z","timestamp":1712415542000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/doi\/10.1093\/bib\/bbae021\/7604886"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,22]]},"references-count":39,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,1,22]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbae021","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"value":"1467-5463","type":"print"},{"value":"1477-4054","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,3,1]]},"published":{"date-parts":[[2024,1,22]]},"article-number":"bbae021"}}