Joint precursor elution profile inference via regression for peptide detection in data-independent acquisition mass spectra

Abstract

In data independent acquisition (DIA) mass spectrometry, precursor scans are interleaved with wide-window fragmentation scans, resulting in complex fragmentation spectra containing multiple co-eluting peptide species. In this setting, detecting the isotope distribution profiles of intact peptides in the precursor scans can be a critical initial step in accurate peptide detection and quantification. This peak detection step is particularly challenging when the isotope peaks associated with two different peptide species overlap--or interfere--with one another. We propose a regression model, called Siren, to detect isotopic peaks in precursor DIA data that can explicitly account for interference. We validate Sirens peak-calling performance on a variety of data sets by counting how many of the peaks Siren identifies are associated with confidently detected peptides. In particular, we demonstrate that substituting the Siren regression model in place of the existing peak-calling step in DIA-Umpire leads to improved overall rates of peptide detection.