Methods for Multiple Alignment and Consensus Structure Prediction of RNAs Implemented in MARNA

Abstract

Multiple alignments of RNAs are an essential prerequisite to further analyses such as homology modeling, motif description, or illustration of conserved or variable binding sites. Beyond the comparison of RNAs on the sequence level, structural conformations determined by basepairs have to be taken into account. Several pairwise sequence-structure alignment methods have been developed. They use extended alignment scores that evaluate secondary structure information in addition to sequence information. However, two problems for the multiple alignment step remain. First, how to combine pairwise sequence-structure alignments into a multiple alignment and, second, how to generate secondary structure information for sequences whose structural information is missing. Here, we describe MARNA, its underlying methods and its usage. MARNA is an approach for multiple alignment of RNAs taking into considerations both the primary sequences and the secondary structures. It relies on the pairwise sequence-structure comparison strategy by generating a set of weighted alignment edges. This set is processed by a consistency-based multiple alignment method. Additionally, MARNA extracts a consensus-sequence and structure from this generated multiple alignment. MARNA can be accessed via the http://www.bioinf.uni-freiburg.de/Software/MARNA.