Abstract

Secondary structure plays an important role in determining the function of noncoding RNAs. Hence, identifying RNA secondary structures is of great value to research. Computational prediction is a mainstream approach for predicting RNA secondary structure. Unfortunately, even though new methods have been proposed over the past 40 years, the performance of computational prediction methods has stagnated in the last decade. Recently, with the increasing availability of RNA structure data, new methods based on machine learning (ML) technologies, especially deep learning, have alleviated the issue. In this review, we provide a comprehensive overview of RNA secondary structure prediction methods based on ML technologies and a tabularized summary of the most important methods in this field. The current pending challenges in the field of RNA secondary structure prediction and future trends are also discussed.

Highlights

  • NcRNA molecules often fold into higher-order structures, and functionally important noncoding RNAs (ncRNA) structures are typically conserved during evolution

  • RNA structure is one of the central pieces of information for understanding biological processes, and determining RNA secondary structure will continue to be a hot topic in the computation and biology fields

  • We focused on machine learning (ML)-based methods, which involve many aspects of RNA secondary structure prediction

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Summary

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Citation: Zhao Q, Zhao Z, Fan X, Yuan Z, Mao Q, Yao Y (2021) Review of machine learning methods for RNA secondary structure prediction. PLoS Comput Biol 17(8): e1009291. https://doi.org/ 10.1371/journal.pcbi.1009291 Funding: This work was supported in part by the Fundamental Research Funds of Northeastern University (N181903008 - Q.Z.); the Research Start-up Fund for Talent of Dalian Maritime University (02500348 - Z.Z.); the Doctoral Scientific Research Foundation of Liaoning Province of China (2019-BS-108 - Q.M.); the Youth Seedling Project of Educational Department of Liaoning Province of China (LQN202002- Q.M.); the Fundamental Research Funds for the Central Universities (82232019 - X.Y.F.); and the National Natural Science Foundation of China (62002056 Q.Z., 31801623 - Q.M., 81871219 - Z.W.Y). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Introduction
Probabilistic approach based on ML
MFT network
Wet lab experiments
Traditional computational methods
Score scheme based on ML
Preprocessing and postprocessing based on ML
Predicting process based on ML
Current pending challenges
Future trends of development
Conclusions
Findings
Supporting information
Full Text
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