{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T13:45:26Z","timestamp":1791812726320,"version":"4.3.4"},"reference-count":26,"publisher":"American Chemical Society (ACS)","issue":"19","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["1U2CES030167-01"],"award-info":[{"award-number":["1U2CES030167-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ionization sources convert neutral analytes into ions, enabling their subsequent separation and detection by mass spectrometry. Depending on the technique, this mechanism occurs within a solution or in the gas phase. The two most common methods to generate ions are electrospray ionization (ESI) and atmospheric-pressure chemical ionization (APCI), respectively. Both ESI and APCI can generate the same resultant ion species; however, it has been shown that preferential charge sites can change in response to an ionization source environment. Therefore, an additional quality control is warranted a priori to delineate erroneous analyte identification and\/or unequivocal structural assignment. For protonation, protomer fidelity can be assessed by comparing the ion-mobility collision cross section (CCS) values obtained for both ESI and APCI. In this work, we utilized proxy standards (i.e., controls) derived from the available literature to develop a proof-of-concept multimodel inference application called AGENTi to probe differences in ionization for high-throughput protomer shift exploratory analysis. AGENTi uses in sequence the TensorFlow Autoencoder anomaly detection and the YDF Gradient Boosted Tree machine learning frameworks to generate more balanced and robust anomaly scores. We found that using a multimodel screening approach can reduce false positive capture at an acceptable loss of true positives. Moreover, we expect to achieve a better recovery of true positives with an improvement on the current Gradient Boosted Tree regression model for \u0394CCS prediction as more ESI-APCI dual data are obtained for training. In all, we demonstrated in this pilot study that our foundation model for a priori probing of ionization pathway fidelity is feasible and efficient with AGENTi. The AGENTi prototype application and documentation are accessible at https:\/\/github.com\/mitkeng\/AGENTi.<\/jats:p>","DOI":"10.1021\/acs.jcim.6c01085","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:02:01Z","timestamp":1790258521000},"page":"12316-12325","source":"Crossref","is-referenced-by-count":0,"title":["AGENTi: APCI-ESI\nAnalyte Ionization Fidelity Pre-Screening\nWorkflow using Multimodel Inference"],"prefix":"10.1021","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9850-0120","authenticated-orcid":true,"given":"Mithony","family":"Keng","sequence":"first","affiliation":[{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Kenneth M","family":"Merz","sequence":"additional","affiliation":[{"name":"Michigan State University , , , ,","place":["East Lansing, Michigan, United States, 48824"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"issue":"11","key":"2026101208073365800_cit1","doi-asserted-by":"publisher","first-page":"2185","DOI":"10.1007\/s13361-019-02288-2","article-title":"Ion Mobility Spectrometry: Fundamental Concepts, Instrumentation,\nApplications, and the Road Ahead","volume":"30","author":"Dodds","year":"2019","journal-title":"J. Am. Soc.\nMass Spectrom."},{"issue":"1","key":"2026101208073365800_cit2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2015\/650927","article-title":"Comparison of Electrospray\nIonization\nand Atmospheric Chemical Ionization Coupled with the Liquid Chromatography-Tandem\nMass Spectrometry for the Analysis of Cholesteryl Esters","volume":"2015","author":"Lee","year":"2015","journal-title":"Int. J. Anal. Chem."},{"key":"2026101208073365800_cit3","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.ijms.2016.09.022","article-title":"Effects of ESI conditions\non kinetic trapping of the solution-phase protonation isomer of p-aminobenzoic\nacid in the gas phase","volume":"418","author":"Patrick","year":"2017","journal-title":"Int. J. Mass Spectrom."},{"issue":"6","key":"2026101208073365800_cit4","doi-asserted-by":"publisher","first-page":"4481","DOI":"10.1039\/D2CP04497H","article-title":"Hydration-induced protomer\nswitching in p-aminobenzoic acid studied\nby cold double ion trap infrared spectroscopy","volume":"25","author":"Akasaka","year":"2023","journal-title":"Phys. Chem. Chem. Phys."},{"issue":"4","key":"2026101208073365800_cit5","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1002\/jms.4066","article-title":"Transformation of the gas-phase favored -protomer of\n-aminobenzoic acid to its unfavored -protomer by ion activation in\nthe presence of water vapor: An ion-mobility mass spectrometry study","volume":"53","author":"Xia","year":"2018","journal-title":"J. Mass Spectrom."},{"issue":"8","key":"2026101208073365800_cit6","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1007\/s13361-017-1640-0","article-title":"Influence of Ionization Source Conditions on the Gas-Phase\nProtomer Distribution of Anilinium and Related Cations","volume":"28","author":"Attygalle","year":"2017","journal-title":"J. Am. Soc. Mass Spectrom."},{"issue":"1","key":"2026101208073365800_cit7","doi-asserted-by":"publisher","first-page":"1644","DOI":"10.1038\/s41598-018-20012-0","article-title":"Characterization of Conformational\nEnsembles of Protonated N-glycans in the Gas-Phase","volume":"8","author":"Re","year":"2018","journal-title":"Sci. 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