2016/04/05 by Phuong Dao, Jan Hoinka, Dao, Phuong +17
Biochemistry, Genetics and Molecular Biology · #Advanced biosensing and bioanalysis techniques #Computational Engineering #FOS: Biological sciences #FOS: Computer and information sciences #Finance #Quantitative Methods (q-bio.QM) #RNA Interference and Gene Delivery #RNA and protein synthesis mechanisms #and Science (cs.CE)
paper · pdf · doi:10.48550/arxiv.1604.03081
openalex publication_date 2016/04/05 · openalex created_date 2019/07/30 · openalex updated_date 2026/07/28
Aptamers, short synthetic RNA/DNA molecules binding specific targets with\nhigh affinity and specificity, are utilized in an increasing spectrum of\nbio-medical applications. Aptamers are identified in vitro via the Systematic\nEvolution of Ligands by Exponential Enrichment (SELEX) protocol. SELEX selects\nbinders through an iterative process that, starting from a pool of random\nssDNA/RNA sequences, amplifies target-affine species through a series of\nselection cycles. HT-SELEX, which combines SELEX with high throughput\nsequencing, has recently transformed aptamer development and has opened the\nfield to even more applications. HT-SELEX is capable of generating over half a\nbillion data points, challenging computational scientists with the task of\nidentifying aptamer properties such as sequence structure motifs that determine\nbinding. While currently available motif finding approaches suggest partial\nsolutions to this question, none possess the generality or scalability required\nfor HT-SELEX data, and they do not take advantage of important properties of\nthe experimental procedure.\n We present AptaTRACE, a novel approach for the identification of\nsequence-structure binding motifs in HT-SELEX derived aptamers. Our approach\nleverages the experimental design of the SELEX protocol and identifies\nsequence-structure motifs that show a signature of selection. Because of its\nunique approach, AptaTRACE can uncover motifs even when these are present in\nonly a minuscule fraction of the pool. Due to these features, our method can\nhelp to reduce the number of selection cycles required to produce aptamers with\nthe desired properties, thus reducing cost and time of this rather expensive\nprocedure. The performance of the method on simulated and real data indicates\nthat AptaTRACE can detect sequence-structure motifs even in highly challenging\ndata.\n