Intensity and retention time prediction improves the rescoring of protein‐nucleic acid cross‐links

Abstract

In protein‐RNA cross‐linking mass spectrometry, UV or chemical cross‐linking introduces stable bonds between amino acids and nucleic acids in protein‐RNA complexes that are then analyzed and detected in mass spectra. This analytical tool delivers valuable information about RNA‐protein interactions and RNA docking sites in proteins, both in vitro and in vivo. The identification of cross‐linked peptides with oligonucleotides of different length leads to a combinatorial increase in search space. We demonstrate that the peptide retention time prediction tasks can be transferred to the task of cross‐linked peptide retention time prediction using a simple amino acid composition encoding, yielding improved identification rates when the prediction error is included in rescoring. For the more challenging task of including fragment intensity prediction of cross‐linked peptides in the rescoring, we obtain, on average, a similar improvement. Further improvement in the encoding and fine‐tuning of retention time and intensity prediction models might lead to further gains, and merit further research.