FastRet: Fast andSimple Retention Time Predictionin Liquid Chromatography

Abstract

Abstract Feature annotation in liquid chromatography–mass spectrometry (LC–MS)-based untargeted metabolomics remains challenging. Retention time (RT) prediction can support candidate prioritization and improve annotation confidence. Here, we present FastRet, an R package predicting RTs using Least Absolute Shrinkage and Selection Operator (LASSO) and Boosted Regression Trees (BRT) on molecular descriptors. FastRet provides a flexible framework combining from-scratch model training, selective measuring to prioritize metabolites for remeasurement, and model adjustment to adapt existing models to changed chromatographic conditions. Model training and prediction are completed within seconds on a single CPU core, and FastRet is accessible both from the R console and through a web interface. We validated FastRet on three in-house data sets covering reversed-phase chromatography (RP; N = 458), RP–anion-exchange mixed-mode chromatography (RP-AXMM; N = 436), and hydrophilic interaction chromatography (HILIC; N = 388), plus one external HILIC data set from the Retip package (N = 970). Using a 2:1 training/test split, BRT models trained from scratch achieved a test-set coefficient of determination (R2) of 0.86, 0.66, and 0.81 for the three in-house data sets. FastRet can also adjust a model to new chromatographic conditions from a few remeasured metabolites: using 25 RP metabolites measured under six modified conditions, adjustment reached R2 of 0.74 to 0.84 on unseen metabolites, a mean 0.22 gain over from-scratch models. Compared with published methods on identical splits, FastRet showed competitive performance for de novo prediction and superior performance in low-data transfer scenarios, while generalizing to 14 external data sets (median held-out R2 0.59). FastRet is available on CRAN with the web interface hosted at https://fastret.spang-lab.de.