In silico target-specific siRNA design based on domain transfer in heterogeneous data.

RNA interference via exogenous small interference RNAs (siRNA) is a powerful tool in gene function study and disease treatment. Designing efficient and specific siRNA on target gene remains the key issue in RNAi. Although various in silico models have been proposed for rational siRNA design, most of...

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Autores principales: Qi Liu, Han Zhou, Kui Zhang, Xiaoxiao Shi, Wei Fan, Ruixin Zhu, Philip S Yu, Zhiwei Cao
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Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2012
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Acceso en línea:https://doaj.org/article/ac4646e23acf431cbf8fbfe95f0d2405
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spelling oai:doaj.org-article:ac4646e23acf431cbf8fbfe95f0d24052021-11-18T08:04:00ZIn silico target-specific siRNA design based on domain transfer in heterogeneous data.1932-620310.1371/journal.pone.0050697https://doaj.org/article/ac4646e23acf431cbf8fbfe95f0d24052012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23284642/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203RNA interference via exogenous small interference RNAs (siRNA) is a powerful tool in gene function study and disease treatment. Designing efficient and specific siRNA on target gene remains the key issue in RNAi. Although various in silico models have been proposed for rational siRNA design, most of them focus on the efficiencies of selected siRNAs, while limited effort has been made to improve their specificities targeted on specific mRNAs, which is related to reducing off-target effects (OTEs) in RNAi. In our study, we propose for the first time that the enhancement of target specificity of siRNA design can be achieved computationally by domain transfer in heterogeneous data sources from different siRNA targets. A transfer learning based method i.e., heterogeneous regression (HEGS) is presented for target-specific siRNA efficacy modeling and feature selection. Based on the model, (1) the target regression model can be built by extracting information from related data in other targets/experiments, thus increasing the target specificity in siRNA design with the help of information from siRNAs binding to other homologous genes, and (2) the potential features correlated to the current siRNA design can be identified even when there is lack of experimental validated siRNA affinity data on this target. In summary, our findings present useful instructions for a better target-specific siRNA design, with potential applications in genome-wide high-throughput screening of effective siRNA, and will provide further insights on the mechanism of RNAi.Qi LiuHan ZhouKui ZhangXiaoxiao ShiWei FanRuixin ZhuPhilip S YuZhiwei CaoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e50697 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Qi Liu
Han Zhou
Kui Zhang
Xiaoxiao Shi
Wei Fan
Ruixin Zhu
Philip S Yu
Zhiwei Cao
In silico target-specific siRNA design based on domain transfer in heterogeneous data.
description RNA interference via exogenous small interference RNAs (siRNA) is a powerful tool in gene function study and disease treatment. Designing efficient and specific siRNA on target gene remains the key issue in RNAi. Although various in silico models have been proposed for rational siRNA design, most of them focus on the efficiencies of selected siRNAs, while limited effort has been made to improve their specificities targeted on specific mRNAs, which is related to reducing off-target effects (OTEs) in RNAi. In our study, we propose for the first time that the enhancement of target specificity of siRNA design can be achieved computationally by domain transfer in heterogeneous data sources from different siRNA targets. A transfer learning based method i.e., heterogeneous regression (HEGS) is presented for target-specific siRNA efficacy modeling and feature selection. Based on the model, (1) the target regression model can be built by extracting information from related data in other targets/experiments, thus increasing the target specificity in siRNA design with the help of information from siRNAs binding to other homologous genes, and (2) the potential features correlated to the current siRNA design can be identified even when there is lack of experimental validated siRNA affinity data on this target. In summary, our findings present useful instructions for a better target-specific siRNA design, with potential applications in genome-wide high-throughput screening of effective siRNA, and will provide further insights on the mechanism of RNAi.
format article
author Qi Liu
Han Zhou
Kui Zhang
Xiaoxiao Shi
Wei Fan
Ruixin Zhu
Philip S Yu
Zhiwei Cao
author_facet Qi Liu
Han Zhou
Kui Zhang
Xiaoxiao Shi
Wei Fan
Ruixin Zhu
Philip S Yu
Zhiwei Cao
author_sort Qi Liu
title In silico target-specific siRNA design based on domain transfer in heterogeneous data.
title_short In silico target-specific siRNA design based on domain transfer in heterogeneous data.
title_full In silico target-specific siRNA design based on domain transfer in heterogeneous data.
title_fullStr In silico target-specific siRNA design based on domain transfer in heterogeneous data.
title_full_unstemmed In silico target-specific siRNA design based on domain transfer in heterogeneous data.
title_sort in silico target-specific sirna design based on domain transfer in heterogeneous data.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/ac4646e23acf431cbf8fbfe95f0d2405
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