AptaTRACE – Elucidation of RNA Sequence-Structure Motifs from Selection Trends in HT-SELEX Experiments

Authors

• P Dao
• J Hoinka
• M Takahashi
• J Zhou
• M Ho
• Y Wang
• F Costa
• JJ Rossi
• R Backofen
• J Burnett
• TM Przytycka

Abstract

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.

Scientific Focus Area: Computational Biology

This page was last updated on Friday, March 26, 2021