RIsearch: fast RNA–RNA interaction search using a simplified nearest-neighbor energy model

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Abstract
Motivation: Regulatory, non-coding RNAs often function by forming a duplex with other RNAs. It is therefore of interest to predict putative RNA–RNA duplexes in silico on a genome-wide scale. Current computational methods for predicting these interactions range from fast complementary-based searches to those that take intramolecular binding into account. Together these methods constitute a trade-off between speed and accuracy, while leaving room for improvement within the context of genome-wide screens. A fast pre-filtering of putative duplexes would therefore be desirable. Results: We present RIsearch, an implementation of a simplified Turner energy model for fast computation of hybridization, which significantly reduces runtime while maintaining accuracy. Its time complexity for sequences of lengths m and n is with a much smaller pre-factor than other tools. We show that this energy model is an accurate approximation of the full energy model for near-complementary RNA–RNA duplexes. RIsearch uses a Smith–Waterman-like algorithm using a dinucleotide scoring matrix which approximates the Turner nearest-neighbor energies. We show in benchmarks that we achieve a speed improvement of at least 2.4× compared with RNAplex, the currently fastest method for searching near-complementary regions. RIsearch shows a prediction accuracy similar to RNAplex on two datasets of known bacterial short RNA (sRNA)–messenger RNA (mRNA) and eukaryotic microRNA (miRNA)–mRNA interactions. Using RIsearch as a pre-filter in genome-wide screens reduces the number of binding site candidates reported by miRNA target prediction programs, such as TargetScanS and miRanda, by up to 70%. Likewise, substantial filtering was performed on bacterial RNA–RNA interaction data. Availability: The source code for RIsearch is available at: http://rth.dk/resources/risearch. Contact: gorodkin@rth.dk Supplementary information: Supplementary data are available at Bioinformatics online.

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