CPred: Charge State Prediction for Modified and Unmodified Peptides in Electrospray Ionization

The mass-to-charge ratio serves as a critical parameter in peptide identification via mass spectrometry, enabling the precise determination of peptide masses and facilitating their differentiation based on unique charge characteristics, especially when peptides are ionized by tools like electrospray ionization, which produces multiply charged ions. We developed a neural network called CPred, which can accurately predict the charge state distribution from +1 to +7 for the modified and unmodified peptides. CPred was trained on the large-scale synthetic training data, consisting of tryptic and non-tryptic peptides, and various fragmentation methods. The model was further evaluated on independent, external test data sets. Results were evaluated through the Pearson correlation coefficient and showed high correlations of up to 0.9997117 between the predicted and acquired charge state distributions. The effect of specifying modifications in the neural network and feature importance was further investigated, revealing the value of modifications and vital peptide properties in holding on to protons. CPreds’ accurate predictions of the charge state distribution can play an essential role in boosting confidence in peptide identifications during rescoring as a novel feature.