title: AptaTRACE Elucidates RNA Sequence-Structure Motifs from Selection Trends in HT-SELEX Experiments.
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.
authors.affiliation: National Center of Biotechnology Information, National Library of Medicine, NIH, Bethesda, MD 20894, USA.
authors.forename: Phuong
authors.initials: P
authors.lastname: Dao
authors.affiliation: National Center of Biotechnology Information, National Library of Medicine, NIH, Bethesda, MD 20894, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Hoinka
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
authors.forename: Jiehua
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Ho
authors.affiliation: National Center of Biotechnology Information, National Library of Medicine, NIH, Bethesda, MD 20894, USA.
authors.forename: Yijie
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Bioinformatics Group, Department of Computer Science, University of Freiburg, Freiburg 79110, Germany.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Costa
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Rossi
authors.affiliation: Bioinformatics Group, Department of Computer Science, University of Freiburg, Freiburg 79110, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Backofen
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
authors.forename: John
authors.initials: J
authors.lastname: Burnett
authors.affiliation: National Center of Biotechnology Information, National Library of Medicine, NIH, Bethesda, MD 20894, USA. Electronic address: przytyck@ncbi.nlm.nih.gov.
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Przytycka
mesh_terms: D052157:Aptamers, Nucleotide; D059372:Nucleotide Motifs; D012313:RNA; D052156:SELEX Aptamer Technique; D017423:Sequence Analysis, RNA
chemical_list: D052157:Aptamers, Nucleotide; D012313:RNA