Peptide Property Prediction for Mass Spectrometry Using AI: An Introduction to State of the Art Models

Abstract

This review explores state of the art machine learning and deep learning models for peptide property prediction in mass spectrometry-based proteomics, including, but not limited to, models for predicting digestibility, retention time, charge state distribution, collisional cross section, fragmentation ion intensities, and detectability. The combination of these models enables not only the in silico generation of spectral libraries but also finds many additional use cases in the design of targeted assays or data-driven rescoring. This review serves as both an introduction for newcomers and an update for experienced researchers aiming to develop accessible and reproducible models for peptide property predictions. Key limitations of the current models, including difficulties in handling diverse post-translational modifications and instrument variability, highlight the need for large-scale, harmonized datasets, and standardized evaluation metrics for benchmarking.