Finding consensus stable local optimal structures for aligned RNA sequences and its application to discovering riboswitch elements.

Many non-coding RNAs (ncRNAs) can fold into alternate native structures and perform different biological functions. The computational prediction of an ncRNA's alternate native structures can be conducted by analysing the ncRNA's energy landscape. Previously, we have developed a computational approach, RNASLOpt, to predict alternate native structures for a single RNA. In this paper, in order to improve the accuracy of the prediction, we incorporate structural conservation information among a family of related ncRNA sequences to the prediction. We propose a comparative approach, RNAConSLOpt, to produce all possible consensus SLOpt stack configurations that are conserved on the consensus energy landscape of a family of related ncRNAs. Benchmarking tests show that RNAConSLOpt can reduce the number of candidate structures compared with RNASLOpt, and can predict ncRNAs' alternate native structures accurately. Moreover, an application of the proposed pipeline to bacteria in Bacillus genus has discovered several novel riboswitch candidates.