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Short interfering RNA (siRNA)-induced RNA interference is an endogenous pathway in sequence-specific gene silencing. The potency of different siRNAs to inhibit a common target varies greatly and features affecting inhibition are of high current interest. The limited success in predicting siRNA potency being reported so far could originate in the small number and the heterogeneity of available datasets in addition to the knowledge-driven, empirical basis on which features thought to be affecting siRNA potency are often chosen. We attempt to overcome these problems by first constructing a meta-dataset of 6483 publicly available siRNAs (targeting mammalian mRNA), the largest to date, and then applying a Bayesian analysis which accommodates feature set uncertainty. A stochastic logistic regression-based algorithm is designed to explore a vast model space of 497 compositional, structural and thermodynamic features, identifying associations with siRNA potency.Our algorithm reveals a number of features associated with siRNA potency that are, to the best of our knowledge, either under reported in literature, such as anti-sense 5' -3' motif 'UCU', or not reported at all, such as the anti-sense 5' -3' motif 'ACGA'. These findings should aid in improving future siRNA potency predictions and might offer further insights into the working of the RNA-induced silencing complex (RISC).

Original publication

DOI

10.1093/bioinformatics/btp284

Type

Journal article

Journal

Bioinformatics (Oxford, England)

Publication Date

07/2009

Volume

25

Pages

1594 - 1601

Addresses

Department of Biochemistry, University of Oxford, Oxford, UK.

Keywords

RNA-Induced Silencing Complex, RNA, Small Interfering, Bayes Theorem, Sequence Analysis, RNA, RNA Interference, Algorithms, Models, Genetic