title: RIsearch2: suffix array-based large-scale prediction of RNA-RNA interactions and siRNA off-targets.
abstract: Intermolecular interactions of ncRNAs are at the core of gene regulation events, and identifying the full map of these interactions bears crucial importance for ncRNA functional studies. It is known that RNA-RNA interactions are built up by complementary base pairings between interacting RNAs and high level of complementarity between two RNA sequences is a powerful predictor of such interactions. Here, we present RIsearch2, a large-scale RNA-RNA interaction prediction tool that enables quick localization of potential near-complementary RNA-RNA interactions between given query and target sequences. In contrast to previous heuristics which either search for exact matches while including G-U wobble pairs or employ simplified energy models, we present a novel approach using a single integrated seed-and-extend framework based on suffix arrays. RIsearch2 enables fast discovery of candidate RNA-RNA interactions on genome/transcriptome-wide scale. We furthermore present an siRNA off-target discovery pipeline that not only predicts the off-target transcripts but also computes the off-targeting potential of a given siRNA. This is achieved by combining genome-wide RIsearch2 predictions with target site accessibilities and transcript abundance estimates. We show that this pipeline accurately predicts siRNA off-target interactions and enables off-targeting potential comparisons between different siRNA designs. RIsearch2 and the siRNA off-target discovery pipeline are available as stand-alone software packages from http://rth.dk/resources/risearch.
authors.affiliation: Center for non-coding RNA in Technology and Health, University of Copenhagen, Grønnegårdsvej 3, 1870 Frederiksberg C, Denmark.|Department of Veterinary Clinical and Animal Science, University of Copenhagen, Grønnegårdsvej 3, 1870 Frederiksberg C, Denmark.
authors.forename: Ferhat
authors.initials: F
authors.lastname: Alkan
authors.affiliation: Center for non-coding RNA in Technology and Health, University of Copenhagen, Grønnegårdsvej 3, 1870 Frederiksberg C, Denmark.|Department of Veterinary Clinical and Animal Science, University of Copenhagen, Grønnegårdsvej 3, 1870 Frederiksberg C, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Wenzel
authors.affiliation: Center for non-coding RNA in Technology and Health, University of Copenhagen, Grønnegårdsvej 3, 1870 Frederiksberg C, Denmark.|Department of Veterinary Clinical and Animal Science, University of Copenhagen, Grønnegårdsvej 3, 1870 Frederiksberg C, Denmark.|Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
authors.forename: Oana
authors.initials: O
authors.lastname: Palasca
authors.affiliation: Institute for Theoretical Chemistry, University of Vienna, Währingerstraße 17, 1090 Wien, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Kerpedjiev
authors.affiliation: Center for non-coding RNA in Technology and Health, University of Copenhagen, Grønnegårdsvej 3, 1870 Frederiksberg C, Denmark.|Department of Veterinary Clinical and Animal Science, University of Copenhagen, Grønnegårdsvej 3, 1870 Frederiksberg C, Denmark.
authors.forename: Anders Frost
authors.initials: AF
authors.lastname: Rudebeck
authors.affiliation: Center for non-coding RNA in Technology and Health, University of Copenhagen, Grønnegårdsvej 3, 1870 Frederiksberg C, Denmark.|Institute for Theoretical Chemistry, University of Vienna, Währingerstraße 17, 1090 Wien, Austria.|Bioinformatics Group, Department of Computer Science & IZBI-Interdisciplinary Center for Bioinformatics & LIFE-Leipzig Research Center for Civilization Diseases & Competence Center for Scalable Data Services and Solutions, University Leipzig, Härtelstraße 16-18, 04107 Leipzig, Germany.|Max Planck Institute for Mathematics in the Sciences, Inselstraße 22, 04103 Leipzig, Germany.|Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM 87501, USA.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Stadler
authors.affiliation: Center for non-coding RNA in Technology and Health, University of Copenhagen, Grønnegårdsvej 3, 1870 Frederiksberg C, Denmark.|Institute for Theoretical Chemistry, University of Vienna, Währingerstraße 17, 1090 Wien, Austria.|Research Group Bioinformatics and Computational Biology, Faculty of Computer Science, University of Vienna, Währingerstraße 17, 1090 Wien, Austria.
authors.forename: Ivo L
authors.initials: IL
authors.lastname: Hofacker
authors.affiliation: Center for non-coding RNA in Technology and Health, University of Copenhagen, Grønnegårdsvej 3, 1870 Frederiksberg C, Denmark.|Department of Veterinary Clinical and Animal Science, University of Copenhagen, Grønnegårdsvej 3, 1870 Frederiksberg C, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Gorodkin
mesh_terms: D000465:Algorithms; D020029:Base Pairing; D001483:Base Sequence; D045744:Cell Line, Tumor; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism; D012984:Software; D059467:Transcriptome
chemical_list: D034741:RNA, Small Interfering; D022661:RNA, Untranslated