{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:43:24Z","timestamp":1792784604014,"version":"4.5.0"},"reference-count":24,"publisher":"American Chemical Society (ACS)","issue":"39","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011033","name":"Thermo Fisher Scientific","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011033","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Evosep Biosystems"},{"name":"Genome Quebec","award":["GQ139250"],"award-info":[{"award-number":["GQ139250"]}],"id":[{"id":"https:\/\/ror.org\/00xhtr962","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Urinary tract infections are among the most common infections in humans, yet their diagnosis still depends on time-consuming workflows based on microbial culture, followed by MALDI-TOF mass spectrometry. Although LC-MS\/MS offers the sensitivity and specificity needed to bypass culture, conventional pipelines depend on lengthy analyses and peptide\/protein identification steps, limiting the throughput and hindering its adoption in clinical settings. Here, we introduce a direct, identification-free LC-MS\/MS workflow that analyzes raw ion signal and produces species-level microbial identification in about 5 min after preparation, fast enough to meet clinical throughput requirements. Our machine learning-enabled raw-signal pipeline bypasses peptide identification entirely, preserving information and eliminating the traditional interpretation stack. Across 15 independent analytical batches covering 28 clinically relevant pathogens, the method achieved high-confidence classification (MCC = 0.86). Applied to 206 clinical urine specimens across three batches, the approach reached 91% accuracy at clinically actionable microbial loads (greater than 105 CFU\/mL) and, critically, 0 false positives in control specimens. The performance was lower for specimens below this threshold. These results show that raw LC-MS\/MS spectra contain sufficient biological information for direct microbial diagnosis, establishing an analytical framework for clinical mass spectrometry. This proof-of-concept demonstrates that rapid, culture-free, fast microbial identification is achievable and positions raw signal inference as a promising direction for next-generation diagnostic mass spectrometry.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c02725","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T07:01:56Z","timestamp":1789974116000},"page":"28810-28823","source":"Crossref","is-referenced-by-count":0,"title":["Rapid Species-Level\nClassification of Urinary Pathogens\nfrom Raw LC-MS\/MS Signals Using Machine Learning"],"prefix":"10.1021","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2515-1633","authenticated-orcid":true,"given":"Simon J.","family":"Pelletier","sequence":"first","affiliation":[{"name":"CHU de Que\u0301bec\u2212Universite\u0301 Laval Research Center , , , ,","place":["Que\u0301bec City, Quebec, Canada, G1V 4G2"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Lacombe-Rastoll","sequence":"additional","affiliation":[{"name":"CHU de Que\u0301bec\u2212Universite\u0301 Laval Research Center , , , ,","place":["Que\u0301bec City, Quebec, Canada, G1V 4G2"]},{"name":"CHU de Que\u0301bec\u2212Universite\u0301 Laval Research Center , , , ,","place":["Que\u0301bec City, Quebec, Canada, G1V 4G2"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Roux-Dalvai","sequence":"additional","affiliation":[{"name":"CHU de Que\u0301bec\u2212Universite\u0301 Laval Research Center , , , ,","place":["Que\u0301bec City, Quebec, Canada, G1V 4G2"]},{"name":"CHU de Que\u0301bec\u2212Universite\u0301 Laval Research Center , , , ,","place":["Que\u0301bec City, Quebec, Canada, G1V 4G2"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6205-888X","authenticated-orcid":true,"given":"Mickae\u0308l","family":"Leclercq","sequence":"additional","affiliation":[{"name":"CHU de Que\u0301bec\u2212Universite\u0301 Laval Research Center , , , ,","place":["Que\u0301bec City, Quebec, Canada, G1V 4G2"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarisse","family":"Gotti","sequence":"additional","affiliation":[{"name":"CHU de Que\u0301bec\u2212Universite\u0301 Laval Research Center , , , ,","place":["Que\u0301bec City, Quebec, Canada, G1V 4G2"]},{"name":"CHU de Que\u0301bec\u2212Universite\u0301 Laval Research Center , , , ,","place":["Que\u0301bec City, Quebec, Canada, G1V 4G2"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eve","family":"Be\u0301rube\u0301","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Infectiologie de l\u2019Universite\u0301 Laval, Axe Maladies Infectieuses et Immunitaires, Centre de Recherche du CHU de Que\u0301bec\u2212Universite\u0301Laval , , ,","place":["Que\u0301bec City, Quebec, Canada, G1V 4G2"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7075-7424","authenticated-orcid":true,"given":"Pascaline","family":"Bories","sequence":"additional","affiliation":[{"name":"CHU de Que\u0301bec\u2212Universite\u0301 Laval Research Center , , , ,","place":["Que\u0301bec City, Quebec, Canada, G1V 4G2"]},{"name":"CHU de Que\u0301bec\u2212Universite\u0301 Laval Research Center , , , ,","place":["Que\u0301bec City, Quebec, Canada, G1V 4G2"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-E\u0300ve","family":"Thibeault","sequence":"additional","affiliation":[{"name":"CHU de Que\u0301bec\u2212Universite\u0301 Laval Research Center , , , ,","place":["Que\u0301bec City, Quebec, Canada, G1V 4G2"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorte B.","family":"Bekker-Jensen","sequence":"additional","affiliation":[{"name":"Evosep Biosystems , ,","place":["Odense, Denmark, DK-5230"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolai","family":"Bache","sequence":"additional","affiliation":[{"name":"Evosep Biosystems , ,","place":["Odense, Denmark, DK-5230"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Bromirski","sequence":"additional","affiliation":[{"name":"ThermoFisher Scientific , ,","place":["Bremen, Germany, 28199"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Isabel","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Infectiologie de l\u2019Universite\u0301 Laval, Axe Maladies Infectieuses et Immunitaires, Centre de Recherche du CHU de Que\u0301bec\u2212Universite\u0301Laval , , ,","place":["Que\u0301bec City, Quebec, Canada, G1V 4G2"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Precioso","sequence":"additional","affiliation":[{"name":"Universite\u0301 Co\u0302te d\u2019Azur, Inria, CNRS, I3S , ,","place":["Nice, France, 06903"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Droit","sequence":"additional","affiliation":[{"name":"CHU de Que\u0301bec\u2212Universite\u0301 Laval Research Center , , , ,","place":["Que\u0301bec City, Quebec, Canada, G1V 4G2"]},{"name":"CHU de Que\u0301bec\u2212Universite\u0301 Laval Research Center , , , ,","place":["Que\u0301bec City, Quebec, Canada, G1V 4G2"]},{"name":"Universite\u0301 Co\u0302te d\u2019Azur, Inria, CNRS, I3S , ,","place":["Nice, France, 06903"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"issue":"5","key":"2026100608081252100_cit1","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/nrmicro3432","article-title":"Urinary Tract Infections:\nEpidemiology, Mechanisms of Infection and Treatment Options","volume":"13","author":"Flores-Mireles","year":"2015","journal-title":"Nat. Rev. Microbiol."},{"issue":"1","key":"2026100608081252100_cit2","doi-asserted-by":"publisher","first-page":"e143","DOI":"10.1017\/ash.2025.10045","article-title":"Assessing\nthe Burden of Outpatient Urinary Tract Infections in the United States:\nAnalysis of Nationwide Ambulatory Data (2016\u20132019)","volume":"5","author":"Advani","year":"2025","journal-title":"Antimicrobial Stewardship & Healthcare Epidemiology: ASHE"},{"issue":"1","key":"2026100608081252100_cit3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.idc.2013.09.003","article-title":"Urinary Tract\nInfection Syndromes: Occurrence, Recurrence, Bacteriology, Risk Factors,\nand Disease Burden","volume":"28","author":"Foxman","year":"2014","journal-title":"Infect. Dis. Clin. North\nAm."},{"issue":"4","key":"2026100608081252100_cit4","first-page":"277","article-title":"The Antibiotic\nResistance Crisis: Part 1: Causes and Threats","volume":"40","author":"Ventola","year":"2015","journal-title":"Pharmacy and Therapeutics"},{"issue":"7","key":"2026100608081252100_cit5","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1179\/2047773215Y.0000000030","article-title":"Antimicrobial Resistance: A Global\nMultifaceted Phenomenon","volume":"109","author":"Prestinaci","year":"2015","journal-title":"Pathog. Glob. Health"},{"issue":"3","key":"2026100608081252100_cit6","doi-asserted-by":"publisher","first-page":"479","DOI":"10.3390\/diagnostics11030479","article-title":"A New Gold\nRush: A Review of Current and Developing Diagnostic Tools for Urinary\nTract Infections","volume":"11","author":"Xu","year":"2021","journal-title":"Diagnostics"},{"key":"2026100608081252100_cit7","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2015.00791","article-title":"MALDI-TOF Mass Spectrometry:\nAn Emerging Technology for Microbial Identification and Diagnosis","volume":"6","author":"Singhal","year":"2015","journal-title":"Front. Microbiol."},{"key":"2026100608081252100_cit8","doi-asserted-by":"publisher","first-page":"e00819-24","DOI":"10.1128\/jcm.00819-24","article-title":"A Lipidomics-Based Method to Eliminate\nNegative Urine Culture in General Population","volume":"62","author":"Nartey","year":"2024","journal-title":"J. Clin. Microbiol."},{"issue":"3","key":"2026100608081252100_cit9","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1093\/clinchem\/hvaf164","article-title":"A Culture-Free Lipidomics-Based\nScreening Test for Uropathogens","volume":"72","author":"Nartey","year":"2026","journal-title":"Clin. Chem."},{"key":"2026100608081252100_cit10","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s15010-016-0910-2","article-title":"Incidence of Urinary Tract Infections and Antibiotic\nResistance in the Outpatient Setting: A Cross-Sectional Study","volume":"45","author":"Rossignol","year":"2017","journal-title":"Infection"},{"issue":"4","key":"2026100608081252100_cit11","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1074\/mcp.TIR118.001132","article-title":"DIAlignR Provides\nPrecise Retention Time Alignment Across Distant Runs in DIA and Targeted\nProteomics","volume":"18","author":"Gupta","year":"2019","journal-title":"Molecular & Cellular Proteomics"},{"issue":"10","key":"2026100608081252100_cit12","doi-asserted-by":"publisher","first-page":"1998","DOI":"10.1111\/jgs.15518","article-title":"Outpatient\nAntibiotic Prescribing for Older Adults in the United States: 2011\nto 2014","volume":"66","author":"Kabbani","year":"2018","journal-title":"J. Am. Geriatr. Soc."},{"issue":"9","key":"2026100608081252100_cit13","doi-asserted-by":"publisher","DOI":"10.5489\/cuaj.7677","article-title":"Accuracy of Molecular Diagnostic Techniques in Patients\nwith a Confirmed Urine Culture: A Systematic Review and Meta-Analysis","volume":"16","author":"Guzman Robledo","year":"2022","journal-title":"Canadian Urological Association Journal"},{"issue":"19","key":"2026100608081252100_cit14","doi-asserted-by":"publisher","first-page":"2469","DOI":"10.3390\/diagnostics15192469","article-title":"Emerging Technologies for the Diagnosis\nof Urinary\nTract Infections: Advances in Molecular Detection and Resistance Profiling","volume":"15","author":"Baimakhanova","year":"2025","journal-title":"Diagnostics"},{"key":"2026100608081252100_cit15","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.euros.2022.08.009","article-title":"Molecular Diagnostic Methods Versus\nConventional Urine\nCulture for Diagnosis and Treatment of Urinary Tract Infection: A\nSystematic Review and Meta-Analysis","volume":"44","author":"Szlachta-McGinn","year":"2022","journal-title":"Eur. Urol.\nOpen Sci."},{"key":"2026100608081252100_cit16","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2026.1745468","article-title":"Urine Volatile\nOrganic Compounds\nProfiling via GC-IMS Combined with Machine Learning: A Powerful Diagnostic\nand Pathogen Differentiation Tool for Urinary Tract Infections","volume":"16","author":"Zheng","year":"2026","journal-title":"Front. Cell. Infect. Microbiol."},{"issue":"11","key":"2026100608081252100_cit17","doi-asserted-by":"publisher","first-page":"7523","DOI":"10.1021\/acs.analchem.9b05806","article-title":"Fast Pathogen Identification\nUsing Single-Cell Matrix-Assisted Laser Desorption\/Ionization-Aerosol\nTime-of-Flight Mass Spectrometry Data and Deep Learning Methods","volume":"92","author":"Papagiannopoulou","year":"2020","journal-title":"Anal. Chem."},{"issue":"12","key":"2026100608081252100_cit18","doi-asserted-by":"publisher","first-page":"2492","DOI":"10.1074\/mcp.TIR119.001559","article-title":"Fast and Accurate Bacterial Species\nIdentification in Urine Specimens Using LC-MS\/MS Mass Spectrometry\nand Machine Learning","volume":"18","author":"Roux-Dalvai","year":"2019","journal-title":"Mol. Cell. Proteomics"},{"issue":"11","key":"2026100608081252100_cit19","doi-asserted-by":"publisher","first-page":"100832","DOI":"10.1016\/j.mcpro.2024.100832","article-title":"LC-SRM Combined\nWith Machine Learning Enables Fast Identification and Quantification\nof Bacterial Pathogens in Urinary Tract Infections","volume":"23","author":"Gotti","year":"2024","journal-title":"Mol. Cell. Proteomics"},{"issue":"11","key":"2026100608081252100_cit20","doi-asserted-by":"publisher","first-page":"2706","DOI":"10.1021\/jasms.4c00189","article-title":"Discrimination\nof Common E. Coli Strains in Urine by Liquid Chromatography\u2013Ion\nMobility\u2013Tandem Mass Spectrometry and Machine Learning","volume":"35","author":"Olajide","year":"2024","journal-title":"J. Am. Soc. Mass Spectrom."},{"issue":"3","key":"2026100608081252100_cit21","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1074\/mcp.O114.039115","article-title":"MzDB: A File\nFormat Using Multiple Indexing Strategies for the Efficient Analysis\nof Large LC-MS\/MS and SWATH-MS Data Sets","volume":"14","author":"Bouyssie","year":"2015","journal-title":"Mol.\nCell. Proteomics"},{"key":"2026100608081252100_cit22","unstructured":"Nguyen, V.; Schulze, S.; Osborne, M. A.\n          Bayesian Optimization\nfor Iterative Learning. In  34th Conference\non Neural Information Processing Systems (NeurIPS 2020), Vancouver,\nCanada, 2019; pp 1\u201311."},{"key":"2026100608081252100_cit23","unstructured":"Lundberg, S. M.; Allen, P. G.; Lee, S.-I.\n          A Unified Approach to Interpreting\nModel Predictions. In  31st Conference on Neural\nInformation Processing Systems (NIPS 2017), Long Beach, CA, USA, 2017; vol. 30, pp 4765\u20134774."},{"issue":"2","key":"2026100608081252100_cit24","doi-asserted-by":"publisher","first-page":"116018","DOI":"10.1016\/j.diagmicrobio.2023.116018","article-title":"Comparison of 3 Diagnostic Platforms\nfor Identification of Bacteria and Yeast from Positive Blood Culture\nBottles","volume":"107","author":"Smith","year":"2023","journal-title":"Diagn. Microbiol. Infect. Dis."}],"container-title":["Analytical\nChemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.analchem.6c02725","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/39\/28810\/68569783\/acs.analchem.6c02725.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/39\/28810\/68569783\/acs.analchem.6c02725.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:49:39Z","timestamp":1791290979000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancham\/article\/98\/39\/28810\/5433642\/Rapid-Species-Level-Classification-of-Urinary"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":24,"journal-issue":{"issue":"39","published-online":{"date-parts":[[2026,9,21]]},"published-print":{"date-parts":[[2026,10,6]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.analchem.6c02725","relation":{},"ISSN":["0003-2700","1520-6882"],"issn-type":[{"value":"0003-2700","type":"print"},{"value":"1520-6882","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]}}}