Fast Deisotoping Algorithm and Its Implementation in the MSFragger Search Engine

Deisotoping,
or the process of removing peaks in a mass spectrum
resulting from the incorporation of naturally occurring heavy isotopes,
has long been used to reduce complexity and improve the effectiveness
of spectral annotation methods in proteomics. We have previously described
MSFragger, an ultrafast search engine for proteomics, that did not
utilize deisotoping in processing input spectra. Here, we present
a new, high-speed parallelized deisotoping algorithm, based on elements
of several existing methods, that we have incorporated into the MSFragger
search engine. Applying deisotoping with MSFragger reveals substantial
improvements to database search speed and performance, particularly
for complex methods like open or nonspecific searches. Finally, we
evaluate our deisotoping method on data from several instrument types
and vendors, revealing a wide range in performance and offering an
updated perspective on deisotoping in the modern proteomics environment.