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

Animals Humans RNA / metabolism Protein Binding Binding Sites / genetics Hydra / genetics Deep Learning
RNA-binding domains RNA-binding proteins machine learning protein-protein interaction network

Journal

Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571

Informations de publication

Date de publication:
20 07 2023
Historique:
received: 03 01 2023
revised: 20 03 2023
accepted: 13 06 2023
medline: 24 7 2023
pubmed: 9 7 2023
entrez: 8 7 2023
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.molcel.2023.06.019 PMID: 37421941
pubmed: 37421941
pii: S1097-2765(23)00466-5
doi: 10.1016/j.molcel.2023.06.019
pii:
doi:

Substances chimiques

RNA 63231-63-0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2595-2611.e11

Subventions

Organisme : NINDS NIH HHS
ID : K22 NS112678
Pays : United States

Informations de copyright

Copyright © 2023 University of California San Diego. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests G.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.

Auteurs

Wenhao Jin (W)

Department 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.

Kristopher W Brannan (KW)

Department 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.

Katannya Kapeli (K)

Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Samuel S Park (SS)

Department 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.

Hui Qing Tan (HQ)

Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Maya L Gosztyla (ML)

Department 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.

Mayuresh Mujumdar (M)

Department 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.

Joshua Ahdout (J)

Department 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.

Bryce Henroid (B)

Department 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.

Katherine Rothamel (K)

Department 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.

Joy S Xiang (JS)

Department 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.

Limsoon Wong (L)

Department of Computer Science, National University of Singapore, Singapore, Singapore.

Gene W Yeo (GW)

Department 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. Electronic address: geneyeo@ucsd.edu.

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Classifications MeSH

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questionsmedicales.fr › Métabolisme › Liaison aux protéines › HydRA: Deep-learning models for predicting...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Sites de fixation › HydRA: Deep-learning models for predicting...
questionsmedicales.fr › Eucaryotes › Animaux › Invertébrés › Cnidaria › Hydrozoa › Hydra › HydRA: Deep-learning models for predicting...
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