Methodology article

RSEARCH: Finding homologs of single structured RNA sequences

Robert J Klein and Sean R Eddy

Howard Hughes Medical Institute & Department of Genetics, Washington University School of Medicine, Saint Louis, Missouri 63110 USA

author email corresponding author email

BMC Bioinformatics 2003, 4:44doi:10.1186/1471-2105-4-44

Published:	22 September 2003

Abstract

Background

For many RNA molecules, secondary structure rather than primary sequence is the evolutionarily conserved feature. No programs have yet been published that allow searching a sequence database for homologs of a single RNA molecule on the basis of secondary structure.

Results

We have developed a program, RSEARCH, that takes a single RNA sequence with its secondary structure and utilizes a local alignment algorithm to search a database for homologous RNAs. For this purpose, we have developed a series of base pair and single nucleotide substitution matrices for RNA sequences called RIBOSUM matrices. RSEARCH reports the statistical confidence for each hit as well as the structural alignment of the hit. We show several examples in which RSEARCH outperforms the primary sequence search programs BLAST and SSEARCH. The primary drawback of the program is that it is slow. The C code for RSEARCH is freely available from our lab's website.

Conclusion

RSEARCH outperforms primary sequence programs in finding homologs of structured RNA sequences.