Summary

TopPIC Suite consists of five software tools for the analysis of top-down mass spectrometry data: TopFD, TopIndex, TopPIC, TopMG, and TopDiff.

• TopFD (Top-down mass spectral Feature Detection) is a software tool for top-down spectral deconvolution and a successor to MS-Deconv. It groups top-down spectral peaks into isotopic envelopes and converts isotopic envelopes to monoisotopic neutral masses. In addition, it extracts proteoform features from LC-MS or CE-MS data.
• TopIndex (Top-down protein sequence database Indexing) generates index files for protein sequence databases. The index files are used in TopPIC and TopMG to speed up proteoform identification by database search.
• TopPIC (Top-down mass spectrometry-based Proteoform Identification and Characterization) identifies and characterizes proteoforms at the proteome level by searching top-down tandem mass spectra against a protein sequence database. TopPIC is a successor to MS-Align+. It efficiently identifies proteoforms with unexpected alterations, such as mutations and post-translational modifications (PTMs), accurately estimates the statistical significance of identifications, and characterizes reported proteoforms with unknown mass shifts. It uses several techniques, such as indexes, spectral alignment, generating function methods, and the modification identification score (MIScore), to increase the speed, sensitivity, and accuracy.
• TopMG (Top-down mass spectrometry-based proteoform identification using Mass Graphs) is a software tool for identifying highly modified proteoforms by searching top-down tandem mass spectra against a protein sequence database. It is capable of identifying proteoforms with multiple variable PTMs and unexpected alterations, such as histone proteoforms and phosphorylated ones. It uses mass graphs, which efficiently represent candidate proteoforms with multiple variable PTMs, to increase the speed and sensitivity in proteoform identification. In addition, approximate spectrum-based filtering methods are employed for protein sequence filtering, and a Markov chain Monte Carlo method (TopMCMC) is used for estimating the statistical significance of identifications.
• TopDiff (Top-down mass spectrometry-based identification of Differentially expressed proteoforms) compares the abundances of proteoforms and finds differentially expressed proteoforms by using identifications of top-down mass spectrometry data of several protein samples.

Release notes