Inferring noncoding RNA families and classes by means of genome-scale structure-based clustering.
The RFAM database defines families of ncRNAs by means of sequence similarities that are sufficient to establish homology. In some cases, such as microRNAs and box H/ACA snoRNAs, functional commonalities define classes of RNAs that are characterized by structural similarities, and typically consist of multiple RNA families. Recent advances in high-throughput transcriptomics and comparative genomics have produced very large sets of putative noncoding RNAs and regulatory RNA signals. For many of them, evidence for stabilizing selection acting on their secondary structures has been derived, and at least approximate models of their structures have been computed. The overwhelming majority of these hypothetical RNAs cannot be assigned to established families or classes. We present here a structure-based clustering approach that is capable of extracting putative RNA classes from genome-wide surveys for structured RNAs. The LocARNA (local alignment of RNA) tool implements a novel variant of the Sankoff algorithm that is sufficiently fast to deal with several thousand candidate sequences. The method is also robust against false positive predictions, i.e., a contamination of the input data with unstructured or nonconserved sequences. We have successfully tested the LocARNA-based clustering approach on the sequences of the RFAM-seed alignments. Furthermore, we have applied it to a previously published set of 3,332 predicted structured elements in the Ciona intestinalis genome (Missal K, Rose D, Stadler PF (2005) Noncoding RNAs in Ciona intestinalis. Bioinformatics 21 (Supplement 2): i77-i78). In addition to recovering, e.g., tRNAs as a structure-based class, the method identifies several RNA families, including microRNA and snoRNA candidates, and suggests several novel classes of ncRNAs for which to date no representative has been experimentally characterized.
Will
Sebastian
S
Bioinformatics Group, Institute of Computer Science, University of Freiburg, Freiburg, Germany.
Reiche
Kristin
K
Hofacker
Ivo L
IL
Stadler
Peter F
PF
Backofen
Rolf
R
D000465:Algorithms; D000818:Animals; D002874:Chromosome Mapping / Q000379:methods*; D002938:Ciona intestinalis / Q000235:genetics*; D005810:Multigene Family / Q000235:genetics*; D022661:RNA, Untranslated / Q000737:chemistry* / Q000145:classification / Q000235:genetics*; D016415:Sequence Alignment / Q000379:methods*; D017423:Sequence Analysis, RNA / Q000379:methods*; D012689:Sequence Homology, Nucleic Acid
D022661:RNA, Untranslated