Mitigating the missing fragmentation problem in de novo peptide sequencing with a two stage graph-based deep learning model

Abstract

Abstract Novel protein discovery and immunopeptidomics depend on highly sensitive de novo peptide sequencing with tandem mass spectrometry. Despite significant improvement using deep learning models, the missing fragmentation problem remains an important hurdle that significantly degrades the performance of de novo peptide sequencing. In this paper, we reveal that in the process of peptide prediction, missing fragmentation results in generating incorrect amino acids within those regions and causes error accumulation thereafter. To tackle this problem, we propose GraphNovo, a two-stage de novo peptide sequencing algorithm based on a graph neural network. GraphNovo focuses on finding the optimal path in the first stage to guide the sequence prediction in the second stage. Our experiments demonstrate that GraphNovo mitigates the effects of missing fragmentation and outperforms the state-of-the-art de novo peptide sequencing algorithms.