Identification of sequence-structure RNA binding motifs for SELEX-derived aptamers.
BACKGROUND
Systematic Evolution of Ligands by EXponential Enrichment (SELEX) represents a state-of-the-art technology to isolate single-stranded (ribo)nucleic acid fragments, named aptamers, which bind to a molecule (or molecules) of interest via specific structural regions induced by their sequence-dependent fold. This powerful method has applications in designing protein inhibitors, molecular detection systems, therapeutic drugs and antibody replacement among others. However, full understanding and consequently optimal utilization of the process has lagged behind its wide application due to the lack of dedicated computational approaches. At the same time, the combination of SELEX with novel sequencing technologies is beginning to provide the data that will allow the examination of a variety of properties of the selection process.


RESULTS
To close this gap we developed, Aptamotif, a computational method for the identification of sequence-structure motifs in SELEX-derived aptamers. To increase the chances of identifying functional motifs, Aptamotif uses an ensemble-based approach. We validated the method using two published aptamer datasets containing experimentally determined motifs of increasing complexity. We were able to recreate the author's findings to a high degree, thus proving the capability of our approach to identify binding motifs in SELEX data. Additionally, using our new experimental dataset, we illustrate the application of Aptamotif to elucidate several properties of the selection process.
National Center for Biotechnology Information, NLM, NIH, 8600 Rockville Pike, Bethesda, MD 20894, USA.
Jan
J
Hoinka
Elena
E
Zotenko
Adam
A
Friedman
Zuben E
ZE
Sauna
Teresa M
TM
Przytycka
D000465:Algorithms; D052157:Aptamers, Nucleotide / Q000737:chemistry*; D019295:Computational Biology / Q000379:methods*; D009690:Nucleic Acid Conformation; D009696:Nucleic Acids / Q000235:genetics; D059372:Nucleotide Motifs; D052156:SELEX Aptamer Technique / Q000379:methods*
D052157:Aptamers, Nucleotide; D009696:Nucleic Acids