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An alternative to the traditional bottom-up proteomics, top-down analysis involves no prior digestion of proteins into their corresponding peptide species before mass spectrometry (MS) analysis. The primary advantage of top-down analysis is that combinations of posttranslational modifications (PTMs) can be localized, detection of degradation products and sequence variants can be determined, which help to solve inference issues (e.g., isoforms, proteoforms). For single proteins, top-down analysis can confirm identity, characterize PTMs. For protein complexes, this approach determines the identity of the individual proteins that make up the complex and PTMs.