Improved Peptide Retention Time Prediction in Liquid Chromatography through Deep Learning

The accuracy of peptide retention time (RT) prediction model in liquid chromatography (LC) is still not sufficient for wider implementation in proteomics practice. Herein, we propose deep learning as an ideal tool to considerably improve this prediction. A new peptide RT prediction tool, DeepRT, was designed using a capsule network model, and the public data sets containing peptides separated by reverse-phase liquid chromatography were used to evaluate the DeepRT performance. Compared with other prevailing RT predictors, DeepRT attained overall improvement in the prediction of peptide RTs with an R2 of ∼0.994. Moreover, DeepRT was able to accommodate to the peptides that were separated by different types of LC, such as strong cation exchange (SCX) and hydrophilic interaction liquid chromatography (HILIC) and to reach the RT prediction with R2 values of ∼0.996 for SCX and ∼0.993 for HILIC, respectively. If a large peptide data set is available for one type of LC, DeepRT can be promoted to DeepRT(+) using transfer learning. Based on a large peptide data set gained from SWATH, DeepRT(+) further elevated the accuracy of RT prediction for peptides in a small data set and enabled a satisfactory prediction upon limited peptides approximating hundreds. Further, DeepRT automatically learns retention-related properties of amino acids under different separation mechanisms, which are well consistent with retention coefficients (Rc) of the amino acids. DeepRT was thus proven to be an improved RT predictor with high flexibility and efficiency. DeepRT is available at https://github.com/horsepurve/DeepRTplus.