Cited by 132Machine Learning in BioinformaticsProtein Structure and DynamicsRNA Research and Splicing

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RNABindRPlus: A Predictor that Combines Machine Learning and Sequence Homology-Based Methods to Improve the Reliability of Predicted RNA-Binding Residues in Proteins

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Walia, Rasna R., Xue, Li C., Wilkins, Katherine, El-Manzalawy, Yasser, Dobbs, Drena, Honavar, Vasant·2014·PLoS ONE

DOI 10.1371/journal.pone.0097725PMC PMC4028231

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Abstract

Protein-RNA interactions are central to essential cellular processes such as protein synthesis and regulation of gene expression and play roles in human infectious and genetic diseases. Reliable identification of protein-RNA interfaces is critical for understanding the structural bases and functional implications of such interactions and for developing effective approaches to rational drug design. Sequence-based computational methods offer a viable, cost-effective way to identify putative RNA-binding residues in RNA-binding proteins. Here we report two novel approaches: (i) HomPRIP, a sequence homology-based method for predicting RNA-binding sites in proteins; (ii) RNABindRPlus, a new method that combines predictions from HomPRIP with those from an optimized Support Vector Machine (SVM) classifier trained on a benchmark dataset of 198 RNA-binding proteins. Although highly reliable, HomPRIP cannot make predictions for the unaligned parts of query proteins and its coverage is limited by the availability of close sequence homologs of the query protein with experimentally determined RNA-binding sites. RNABindRPlus overcomes these limitations. We compared the performance of HomPRIP and RNABindRPlus with that of several state-of-the-art predictors on two test sets, RB44 and RB111. On a subset of proteins for which homologs with experimentally determined interfaces could be reliably identified, HomPRIP outperformed all other methods achieving an MCC of 0.63 on RB44 and 0.83 on RB111. RNABindRPlus was able to predict RNA-binding residues of all proteins in both test sets, achieving an MCC of 0.55 and 0.37, respectively, and outperforming all other methods, including those that make use of structure-derived features of proteins. More importantly, RNABindRPlus outperforms all other methods for any choice of tradeoff between precision and recall. An important advantage of both HomPRIP and RNABindRPlus is that they rely on readily available sequence and sequence-derived features of RNA-binding proteins. A webserver implementation of both methods is freely available at http://einstein.cs.iastate.edu/RNABindRPlus/.

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Authors: Walia, R. R., Xue, L. C., Wilkins, K., El-Manzalawy, Y., Dobbs, D., & Honavar, V.
Affiliations: Iowa State University (US)
Pennsylvania State University (US)
Cornell University (US)
Corresponding author: Walia, Rasna R.
ORCID: Walia, Rasna R.
Xue, Li C.
Dobbs, Drena
Honavar, Vasant
Venue: PLoS ONE
Publisher: Public Library of Science (PLoS)
Published: 2014-05-20
Volume: 9
Issue: 5
Pages: e97725
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0097725
PMC: PMC4028231
OpenAlex: W2116498086
Cited by: 132
References: 72
Citations by year: 2026: 14 · 2025: 14 · 2024: 14 · 2023: 11 · 2022: 8 · 2021: 10 · 2020: 11 · 2019: 10 · 2018: 14 · 2017: 8 · 2016: 8 · 2015: 10
FWCI: 3.55
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS ONE (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, other-oa)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Iowa State University Digital Repository (Iowa State University) (submittedVersion, other-oa)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Science Foundation (0504304)
Iowa State University
National Institutes of Health (GM066387)
National Institute of General Medical Sciences (R33GM066387, GM 066387, R21GM066387)
Division of Graduate Education
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Machine Learning in Bioinformatics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords: RNA-binding residues, RNA-binding proteins, RNA-protein interactions, RNA-binding site prediction, support vector classifier, sequence homology, sequence-derived features, protein-RNA interface, web server
MeSH terms: Animals, Artificial Intelligence, Humans, Models, Theoretical, RNA-Binding Proteins, Sequence Analysis, RNA, Sequence Analysis, Protein

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RNABindRPlus: A Predictor that Combines Machine Learning and Sequence Homology-Based Methods to Improve the Reliability of Predicted RNA-Binding Residues in Proteins

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