RNA-RNA interaction prediction based on multiple sequence alignments

TL;DR

The paper introduces ripalign, an algorithm that predicts RNA-RNA interactions by integrating thermodynamic stability with evolutionary information from multiple sequence alignments, providing detailed probabilistic and structural outputs.

Contribution

It presents ripalign, a novel method that incorporates multiple sequence alignments into RNA-RNA interaction prediction, enhancing accuracy by considering evolutionary covariation.

Findings

ripalign computes partition functions and base-pairing probabilities effectively.

It requires minimal additional memory compared to single-sequence algorithms.

The method allows incorporation of structural constraints.

Abstract

Many computerized methods for RNA-RNA interaction structure prediction have been developed. Recently, $O(N^6)$ time and $O(N^4)$ space dynamic programming algorithms have become available that compute the partition function of RNA-RNA interaction complexes. However, few of these methods incorporate the knowledge concerning related sequences, thus relevant evolutionary information is often neglected from the structure determination. Therefore, it is of considerable practical interest to introduce a method taking into consideration both thermodynamic stability and sequence covariation. We present the \emph{a priori} folding algorithm \texttt{ripalign}, whose input consists of two (given) multiple sequence alignments (MSA). \texttt{ripalign} outputs (1) the partition function, (2) base-pairing probabilities, (3) hybrid probabilities and (4) a set of Boltzmann-sampled suboptimal structures consisting of canonical joint structures that are compatible to the alignments. Compared to the single sequence-pair folding algorithm \texttt{rip}, \texttt{ripalign} requires negligible additional memory resource. Furthermore, we incorporate possible structure constraints as input parameters into our algorithm. The algorithm described here is implemented in C as part of the \texttt{rip} package. The supplemental material, source code and input/output files can freely be downloaded from \url{http://www.combinatorics.cn/cbpc/ripalign.html}. \section{Contact} Christian Reidys \texttt{duck@santafe.edu}