Large scale analysis of the mutational landscape in HT-SELEX improves aptamer discovery.
Large scale analysis of the mutational landscape in HT-SELEX improves aptamer discovery.
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DOI:
10.1093/nar/gkv308
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发表时间:
2015-07-13
影响因子:
14.9
通讯作者:
Przytycka TM
中科院分区:
文献类型:
--
作者:
Hoinka J;Berezhnoy A;Dao P;Sauna ZE;Gilboa E;Przytycka TM
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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影响因子:
3.5
作者:
JOYCE, GF
通讯作者:
JOYCE, GF
DOI:
10.1073/pnas.1009331107
发表时间:
2010-08-31
影响因子:
11.1
作者:
Cho, Minseon;Xiao, Yi;Soh, H. Tom
通讯作者:
Soh, H. Tom
影响因子:
2.7
作者:
Hoon, Shawn;Zhou, Bin;Scolnick, Jonathan
通讯作者:
Scolnick, Jonathan
影响因子:
3.7
作者:
Kupakuwana GV;Crill JE 2nd;McPike MP;Borer PN
通讯作者:
Borer PN
影响因子:
56.9
作者:
Barabási, AL;Albert, R
通讯作者:
Albert, R