Introduction

Aptamers, short RNA or DNA molecules that bind distinct targets with high affinity and specificity, can be identified using high-throughput systematic evolution of ligands by exponential enrichment (HT-SELEX), but scalable analytic tools for understanding sequence-function relationships from diverse HT-SELEX data are not available. Here we present AptaTRACE, a computational approach that leverages the experimental design of the HT-SELEX protocol, RNA secondary structure, and the potential presence of many secondary motifs to identify sequence-structure motifs that show a signature of selection. We apply AptaTRACE to identify nine motifs in C-C chemokine receptor type 7 targeted by aptamers in an in vitro cell-SELEX experiment. We experimentally validate two aptamers whose binding required both sequence and structural features. AptaTRACE can identify low-abundance motifs, and we show through simulations that, because of this, it could lower HT-SELEX cost and time by reducing the number of selection cycles required.

Publications

  1. AptaTRACE Elucidates RNA Sequence-Structure Motifs from Selection Trends in HT-SELEX Experiments.
    Cite this
    Dao P, Hoinka J, Takahashi M, Zhou J, Ho M, Wang Y, Costa F, Rossi JJ, Backofen R, Burnett J, Przytycka TM, 2016-07-01 - Cell systems

Credits

  1. Phuong Dao
    Developer

    National Center of Biotechnology Information, National Library of Medicine, United States of America

  2. Jan Hoinka
    Developer

    National Center of Biotechnology Information, National Library of Medicine, United States of America

  3. Mayumi Takahashi
    Developer

    Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, United States of America

  4. Jiehua Zhou
    Developer

    Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, United States of America

  5. Michelle Ho
    Developer

    Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, United States of America

  6. Yijie Wang
    Developer

    National Center of Biotechnology Information, National Library of Medicine, United States of America

  7. Fabrizio Costa
    Developer

    Bioinformatics Group, Department of Computer Science, Germany

  8. John J Rossi
    Developer

    Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, United States of America

  9. Rolf Backofen
    Developer

    Bioinformatics Group, Department of Computer Science, Germany

  10. John Burnett
    Developer

    Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, United States of America

  11. Teresa M Przytycka
    Investigator

    National Center of Biotechnology Information, National Library of Medicine, United States of America

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Summary
AccessionBT004300
Tool TypeApplication
Category
PlatformsLinux/Unix
TechnologiesC++
User InterfaceTerminal Command Line
Download Count0
Country/RegionUnited States of America
Submitted ByTeresa M Przytycka