title: Reconsideration of in silico siRNA design from a perspective of heterogeneous data integration: problems and solutions.
abstract: The success of RNA interference (RNAi) depends on the interaction between short interference RNAs (siRNAs) and mRNAs. Design of highly efficient and specific siRNAs has become a challenging issue in applications of RNAi. Here, we present a detailed survey on the state-of-the-art siRNAs design, focusing on several key issues with the current in silico RNAi studies, including: (i) inconsistencies among the proposed guidelines for siRNAs design and the incomplete list of siRNAs features, (ii) improper integration of the heterogeneous cross-platform siRNAs data, (iii) inadequate consideration of the binding specificity of the target mRNAs and (iv) reduction in the 'off-target' effect in siRNAs design. With these considerations, the popular in silico siRNAs design rules are reexamined and several inconsistent viewpoints toward siRNAs feature identifications are clarified. In addition, novel computational models for siRNAs design using state-of-art machine learning techniques are discussed, which focus on heterogeneous data integration, joint feature selection and customized siRNAs screening toward highly specific targets. We believe that addressing such issues in siRNA study will provide new clues for further improved design of more efficient and specific siRNAs in RNAi.
authors.affiliation: Department of Biochemistry and Molecular Biology A110, Life Science Building, 120 Green Street, University of Georgia, Athens, GA 30602-7229, USA. Tel.: +706-542-9779; Fax: +706-542-9751/7782; xyn@bmb.uga.edu; Zhiwei Cao, School of Life Sciences and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China. Tel.: +86-21-54065003; Fax: +86-21-65980296; E-mail: zwcao@tongji.edu.cn.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Han
authors.initials: H
authors.lastname: Zhou
authors.forename: Ruixin
authors.initials: R
authors.lastname: Zhu
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Cao
mesh_terms: D001185:Artificial Intelligence; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D017076:Computer-Aided Design; D005821:Genetic Techniques; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*
chemical_list: D034741:RNA, Small Interfering