biostudies-literatureDuerr VWaters Corporation through iCASE partnership PhD programmesMedical Research CentreEuropean CommissionBiotechnology and Biological Sciences Research CouncilEngineering and Physical Sciences Research Councile70168https://www.ebi.ac.uk/biostudies/studies/S-EPMC12102732biostudies-literatureUnknown34(6)Hydrogen/deuterium exchange-mass spectrometry (HDX-MS) is a powerful tool for studying protein structure and dynamics. As a bottom-up LC-MS technique, its success largely depends on peptide identifications made by peptide mapping prior to HDX measurements. We previously demonstrated that combining peptide mapping results from complementary single- and multipass cyclic ion mobility-mass spectrometry (cIM-MS) experiments, an approach we term "multi-sequence" cIM-MS, can enhance HDX-MS by increasing peptide identifications. However, this approach required labor-intensive, manual handling of the acquired data, including lengthy optimization of drift time (DT) versus DT full width half maximum (FWHM) trendlines during peak detection processing to combat cyclic wrap-around effects. Here, we presProtein science : a publication of the Protein SocietyMultiPassMerger: Automated data processing for multipass cyclic ion mobility HDX-MS.PMC12102732101183630MR/X013030/1EP/V011715/1BB/V006487/2BB/Y004981/1Politis ADuerr VGriffiths DfalseMultiPassMerger: Automated data processing for multipass cyclic ion mobility HDX-MS.Hydrogen/deuterium exchange-mass spectrometry (HDX-MS) is a powerful tool for studying protein structure and dynamics. As a bottom-up LC-MS technique, its success largely depends on peptide identifications made by peptide mapping prior to HDX measurements. We previously demonstrated that combining peptide mapping results from complementary single- and multipass cyclic ion mobility-mass spectrometry (cIM-MS) experiments, an approach we term "multi-sequence" cIM-MS, can enhance HDX-MS by increasing peptide identifications. However, this approach required labor-intensive, manual handling of the acquired data, including lengthy optimization of drift time (DT) versus DT full width half maximum (FWHM) trendlines during peak detection processing to combat cyclic wrap-around effects. Here, we pres2025-01-01T00:00:00Z2025 Jun2026-06-01T11:36:48.496Z2026-04-08T11:56:45.722ZS-EPMC121027324041137710.1002/pro.70168