FAST MS: Software\nfor the Automated Analysis of Top-Down\nMass Spectra of Polymeric Molecules Including RNA, DNA, and Proteins

Top-down mass spectrometry (MS) enables comprehensive\ncharacterization of\nmodified proteins and nucleic acids and, when native electrospray\nionization (ESI) is used, binding site mapping of their complexes\nwith native or therapeutic ligands. However, the high complexity of\ntop-down MS spectra poses a serious challenge to both manual and automated\ndata interpretation, even when the protein, RNA, or DNA sequence and\nthe type of modification or the ligand are known. Here, we introduce\nFAST MS, a user-friendly software that identifies, assigns and relatively\nquantifies signals of molecular and fragment ions in MS and MS/MS\nspectra of biopolymers with known sequence and provides a toolbox\nfor statistical analysis. FAST MS searches mass spectra for ion signals\nby comparing all signals in the spectrum with isotopic profiles calculated\nfrom known sequences, resulting in superior sensitivity and an increased\nnumber of assigned fragment ions compared to algorithms that rely\non artificial monomer units while maintaining the false positive rate\non a moderate level (<5%). FAST MS is an open-source, cross-platform\nsoftware for the accurate identification, localization and relative\nquantification of modifications, even in complex mixtures of positional\nisomers of proteins, oligonucleotides, or any other user-defined linear\npolymer.