Automatic deconvolution of isotope-resolved mass spectra using variable selection and quantized peptide mass distribution.

We present an algorithm for the deconvolution of isotope-resolved mass spectra of complex peptide mixtures where peaks and isotope series often overlap. The algorithm formulates the problem of mass spectrum deconvolution as a classical statistical problem of variable selection, which aims to interpret the spectrum with the least number of peptides. The LASSO method is used to perform automatic variable selection. The algorithm also makes use of the quantized distribution of peptide masses in the NCBInr database after in silico trypsin digestion as filters to aid the deconvolution process. Errors in the expected isotope pattern are accounted for to avoid spurious isotope series. The effectiveness of the algorithm is demonstrated with annotated ESI spectrum of known peptides for which the peaks and isotope series are highly overlapping. The algorithm successfully finds all correct masses in the experimental spectrum, except for one spectrum where an additional refinement procedure is required to obtain the correct results. Our results compare favorably to those from a widely used commercial program.