Alpha-XIC: a deep neural network for scoring the coelution of peak groups improves peptide identification by data-independent acquisition mass spectrometry.

Abstract

The peptide-centric identification methodologies of data-independent acquisition (DIA) data mainly rely on scores for the mass spectrometric signals of targeted peptides. Among these scores, the coelution scores of peak groups constructed by the chromatograms of peptide fragment ions have a significant influence on the identification. Most of the existing coelution scores are achieved by artificially designing some functions in terms of the shape similarity, retention time shift of peak groups. However, these scores cannot characterize the coelution robustly when the peak group is in the circumstance of interference. On the basis that the neural network is more powerful to learn the implicit features of data robustly from a large number of samples, and thus minimizing the influence of data noise, in this work, we propose Alpha-XIC, a neural network-based model to score the coelution. By learning the characteristics of the coelution of peak groups derived from the being analyzed DIA data, Alpha-XIC is capable of yielding robust coelution scores even for peak groups with interference. With this score appending to initial scores generated by the accompanying identification engine DIA-NN, the ensuing statistical validation can report the identification result and recover the misidentified peptides. In our evaluation of the HeLa dataset with gradient lengths ranging from 0.5 to 2 h, Alpha-XIC delivered 9.4-16.2% improvements in the number of identified precursors at 1% false discovery rate. Furthermore, Alpha-XIC was tested on LFQbench, a mixed-species dataset with known ratios, and increased the number of peptides and proteins fell within valid ratios by up to 16.4% and 17.8%, respectively, compared to the initial identification by DIA-NN. Source code is available at https://github.com/YuAirLab/Alpha-XIC.