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Updated: Jul 24, 2025

Sample Preparation for Mass Spectrometry-based Identification of RNA-binding Regions
Published on: September 28, 2017
HydRA: Deep-learning models for predicting RNA-binding capacity from protein interaction association context and
Wenhao Jin1, Kristopher W Brannan1, Katannya Kapeli2
1Department of Cellular and Molecular Medicine, University of Califorinia, San Diego, La Jolla, CA, USA; Institute for Genomic Medicine and UCSD Stem Cell Program, University of California, San Diego, La Jolla, CA, USA; Stem Cell Program, University of California, San Diego, La Jolla, CA, USA.
Abstract:
RNA-binding proteins (RBPs) control RNA metabolism to orchestrate gene expression and, when dysfunctional, underlie human diseases. Proteome-wide discovery efforts predict thousands of RBP candidates, many of which lack canonical RNA-binding domains (RBDs). Here, we present a hybrid ensemble RBP classifier (HydRA), which 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 machines (SVMs), convolutional neural networks (CNNs), and Transformer-based protein language models. Occlusion mapping by HydRA robustly detects known RBDs and predicts hundreds of uncharacterized RNA-binding associated domains. Enhanced CLIP (eCLIP) for HydRA-predicted RBP candidates reveals transcriptome-wide RNA targets and confirms RNA-binding activity for HydRA-predicted RNA-binding associated domains. HydRA accelerates construction of a comprehensive RBP catalog and expands the diversity of RNA-binding associated domains.
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