The field of proteomics is increasingly concerned with the diversity and functional relevance of protein modifications. Differential ion mobility spectrometry (DMS) is emerging as a tool to detect and quantify additional peptide and protein species that are difficult to analyse with conventional instrumental methods. In this review, recent advances in DMS are discussed, with a focus on the different types of DMS instruments now available to researchers in proteomics. Furthermore, the combination of DMS with mass spectrometry (MS) for increased proteome coverage and the targeted analysis of modification patterns on single proteins is highlighted. Frontier areas of research, such as the analysis of intact proteoforms, and future directions for the implementation of DMS in proteomics are also discussed.
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