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.

Automated summary

Deisotoping, the removal of peaks in mass spectra caused by natural heavy isotopes, is crucial for reducing complexity and improving performance in proteomics research. A new parallelized deisotoping algorithm integrated into the MSFragger search engine shows significant enhancements in database search speed and performance, especially for complex search methods. Evaluation of the deisotoping method on data from various instruments and vendors provides a comprehensive perspective on its performance and relevance in modern proteomics.