Fast and Accurate Charge State Deconvolution of Protein Mass Spectra.

Charge state deconvolution is essential for efficient and effective protein mass spectrometry analysis. High-quality mass profiling is necessary to determine which proteoforms are present in protein samples and their relative abundances. In the pursuit of a well-rounded deconvolution solution, we detail an iterative charge state deconvolution algorithm named kDecon that has been tuned to provide high accuracy in its mass results while also delivering superb sensitivity toward lower abundance proteoforms in complex spectra. Here, the performance of kDecon as a mass determination algorithm for both targeted antibody and high-throughput proteomics analysis was benchmarked against existing deconvolution solutions. While the different deconvolution routines all proved robust for detecting the highest abundance protein species, kDecon ultimately showcased best-in-class precision for lower abundance proteoform mass profiling. Furthermore, kDecon results had up to 7-fold fewer false positives and simultaneously exhibited at least 20-fold speed improvements over the other algorithms. Overall, these deconvolution advances will contribute to enabling both routine and thorough intact mass profiling studies for biotherapeutics as well as improving the proteome coverage of top-down proteomics experiments.