Direct RNA motif definition and identification from multiple sequence alignments using secondary structure profiles

We present here a new approach to the problem of defining RNA signatures an d finding their occurrences in sequence databases. TI-le proposed method is based on "secondary structure profiles". An RNA sequence alignment with se condary structure information is used as an input. Two types of weight matr ices/profiles are constructed from this alignment: single strands are repre sented by a classical lod-scores profile while helical regions are represen ted by an extended "helical profile" comprising 16 lod-scores per position, one for each of the 16 possible base-pairs. Database searches are then con ducted using a simultaneous search for helical profiles and dynamic program ming alignment of single strand profiles. The algorithm has been implemente d into a new software, ERPIN, that performs both profile construction and d atabase search. Applications are presented for several RNA motifs. The auto mated use of sequence information in both single-stranded and helical regio ns yields better sensitivity/specificity ratios than descriptor-based progr ams. Furthermore, since the translation of alignments into profiles is stra ightforward with ERPIN, iterative searches can easily be conducted to enric h collections of homologous RNAs. (C) 2001 Academic Press.