Top-down mass spectrometry is the method of choice for identification and characterization of complex proteoforms with multiple changes, such as mutations and post-translational modifications. Because of advances in protein separation and mass spectrometry, top-down mass spectrometry moved from analyzing single proteins to analyzing complex samples and identifying hundreds and even thousands of proteins.
TopPIC (TOP-Down Mass Spectrometry Based Proteoform Identification and Characterization) is a software tool for identification and characterization of proteoforms at the whole proteome level by top-down tandem mass spectra using database search. It efficiently identifies proteoforms with unexpected mutations and post-translational modifications and accurately estimates statistical significance of identifications. It uses several techniques, such indexes, spectral alignment, and a generation function method, to increase its speed, sensitivity, and accuracy.