Introduction

Structure dictates the function of many RNAs, but secondary RNA structure analysis is either labor intensive and costly or relies on computational predictions that are often inaccurate. These limitations are alleviated by integration of structure probing data into prediction algorithms. However, existing algorithms are optimized for a specific type of probing data. Recently, new chemistries combined with advances in sequencing have facilitated structure probing at unprecedented scale and sensitivity. These novel technologies and anticipated wealth of data highlight a need for algorithms that readily accommodate more complex and diverse input sources. We implemented and investigated a recently outlined probabilistic framework for RNA secondary structure prediction and extended it to accommodate further refinement of structural information. This framework utilizes direct likelihood-based calculations of pseudo-energy terms per considered structural context and can readily accommodate diverse data types and complex data dependencies. We use real data in conjunction with simulations to evaluate performances of several implementations and to show that proper integration of structural contexts can lead to improvements. Our tests also reveal discrepancies between real data and simulations, which we show can be alleviated by refined modeling. We then propose statistical preprocessing approaches to standardize data interpretation and integration into such a generic framework. We further systematically quantify the information content of data subsets, demonstrating that high reactivities are major drivers of SHAPE-directed predictions and that better understanding of less informative reactivities is key to further improvements. Finally, we provide evidence for the adaptive capability of our framework using mock probe simulations.

Publications

  1. Data-directed RNA secondary structure prediction using probabilistic modeling.
    Cite this
    Deng F, Ledda M, Vaziri S, Aviran S, 2016-08-01 - RNA (New York, N.Y.)

Credits

  1. Fei Deng
    Developer

    Department of Biomedical Engineering and Genome Center, University of California at Davis, United States of America

  2. Mirko Ledda
    Developer

    Department of Biomedical Engineering and Genome Center, University of California at Davis, United States of America

  3. Sana Vaziri
    Developer

    Department of Biomedical Engineering and Genome Center, University of California at Davis, United States of America

  4. Sharon Aviran
    Investigator

    Department of Biomedical Engineering and Genome Center, University of California at Davis, United States of America

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Summary
AccessionBT003783
Tool TypeApplication
Category
PlatformsLinux/Unix
TechnologiesC
User InterfaceTerminal Command Line
Download Count0
Country/RegionUnited States of America
Submitted BySharon Aviran