Comprehensive Survey and Comparative Assessment of RNA-Binding Residue Predictions with Analysis by RNA Type

With close to 30 sequence-based predictors of RNA-binding residues (RBRs), this comparative survey aims to help with understanding and selection of the appropriate tools. We discuss past reviews on this topic, survey a comprehensive collection of predictors, and comparatively assess six representative methods. We provide a novel and well-designed benchmark dataset and we are the first to report and compare protein-level and datasets-level results, and to contextualize performance to specific types of RNAs. The methods considered here are well-cited and rely on machine learning algorithms on occasion combined with homology-based prediction. Empirical tests reveal that they provide relatively accurate predictions. Virtually all methods perform well for the proteins that interact with rRNAs, some generate accurate predictions for mRNAs, snRNA, SRP and IRES, while proteins that bind tRNAs are predicted poorly. Moreover, except for DRNApred, they confuse DNA and RNA-binding residues. None of the six methods consistently outperforms the others when tested on individual proteins. This variable and complementary protein-level performance suggests that users should not rely on applying just the single best dataset-level predictor. We recommend that future work should focus on the development of approaches that facilitate protein-level selection of accurate predictors and the consensus-based prediction of RBRs.