TopFD: A Proteoform Feature Detection Tool for Top-Down Proteomics

Top-down liquid chromatography-mass spectrometry (LC-MS)analyzesintact proteoforms and generates mass spectra containing peaks ofproteoforms with various isotopic compositions, charge states, andretention times. An essential step in top-down MS data analysis isproteoform feature detection, which aims to group these peaks intopeak sets (features), each containing all peaks of a proteoform. Accurateprotein feature detection enhances the accuracy in MS-based proteoformidentification and quantification. Here, we present TopFD, a softwaretool for top-down MS feature detection that integrates algorithmsfor proteoform feature detection, feature boundary refinement, andmachine learning models for proteoform feature evaluation. We performedextensive benchmarking of TopFD, ProMex, FlashDeconv, and Xtract usingseven top-down MS data sets and demonstrated that TopFD outperformsother tools in feature accuracy, reproducibility, and feature abundancereproducibility.