期刊
NUCLEIC ACIDS RESEARCH
卷 43, 期 12, 页码 5699-5707出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkv308
关键词
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资金
- Intramural Research Program of the National Institutes of Health, National Library of Medicine
- Laboratory of Hemostasis
- Center for Biologics Evaluation and Research, Food and Drug Administration's Chief Scientist Challenge Grant
- Dodson estate
- Sylvester Comprehensive Cancer Center, Medical School, University of Miami
- National Institutes of Health
High-Throughput (HT) SELEX combines SELEX (Systematic Evolution of Ligands by EXponential Enrichment), a method for aptamer discovery, with massively parallel sequencing technologies. This emerging technology provides data for a global analysis of the selection process and for simultaneous discovery of a large number of candidates but currently lacks dedicated computational approaches for their analysis. To close this gap, we developed novel in-silico methods to analyze HT-SELEX data and utilized them to study the emergence of polymerase errors during HT-SELEX. Rather than considering these errors as a nuisance, we demonstrated their utility for guiding aptamer discovery. Our approach builds on two main advancements in aptamer analysis: AptaMut--a novel technique allowing for the identification of polymerase errors conferring an improved binding affinity relative to the 'parent' sequence and AptaCluster--an aptamer clustering algorithm which is to our best knowledge, the only currently available tool capable of efficiently clustering entire aptamer pools. We applied these methods to an HT-SELEX experiment developing aptamers against Interleukin 10 receptor alpha chain (IL-10RA) and experimentally confirmed our predictions thus validating our computational methods.
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