HydRA: Deep-learning models for predicting RNA-binding capacity from protein interaction association context and protein sequence

• Published in: bioRxiv
• Main Authors: Jin, Wenhao, Brannan, Kristopher W, Kapeli, Katannya, Park, Samuel S, Tan, Hui Qing, Gosztyla, Maya L, Mujumdar, Mayuresh, Ahdout, Joshua, Henroid, Bryce, Rothamel, Katherine, Xiang, Joy S, Wong, Limsoon, Yeo, Gene W
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 24.12.2022
• Subjects: Amino acid sequence; Computer applications; Gene expression; Gene mapping; Genomes; Neural networks; Nucleotide sequence; Peptide mapping; Protein interaction; Proteins; Proteomes; Ribonucleic acid; RNA; RNA-binding protein
• DOI: 10.1101/2022.12.23.521837

RNA-binding proteins (RBPs) control RNA metabolism to orchestrate gene expression, and dysfunctional RBPs underlie many human diseases. Proteome-wide discovery efforts predict thousands of novel RBPs, many of which lack canonical RNA-binding domains. Here, we present a hybrid ensemble RBP classifier (HydRA) that leverages information from both intermolecular protein interactions and internal protein sequence patterns to predict RNA-binding capacity with unparalleled specificity and sensitivity using support vector machine, convolutional neural networks and transformer-based protein language models. HydRA enables Occlusion Mapping to robustly detect known RNA-binding domains and to predict hundreds of uncharacterized RNA-binding domains. Enhanced CLIP validation for a diverse collection of RBP candidates reveals genome-wide targets and confirms RNA-binding activity for HydRA-predicted domains. The HydRA computational framework accelerates construction of a comprehensive RBP catalogue and expands the set of known RNA-binding protein domains.Competing Interest StatementG.W.Y. is a co-founder, member of the Board of Directors, on the SAB, equity holder, and paid consultant for Locanabio and Eclipse BioInnovations. G.W.Y. is a visiting professor at the National University of Singapore. G.W.Y.'s interests have been reviewed and approved by the University of California, San Diego in accordance with its conflict-of-interest policies. The authors declare no other competing financial interests.Footnotes* We added a new affiliation for co-author Kristopher W. Brannan in the author list and the manuscript file.