Concurrent prediction of RNA secondary structures with pseudoknots and local 3D motifs in an integer programming framework

Abstract

Abstract Motivation The prediction of RNA structure canonical base pairs from a single sequence, especially pseudoknotted ones, remains challenging in a thermodynamic models that approximates the energy of the local 3D motifs joining canonical stems. It has become more and more apparent in recent years that the structural motifs in the loops, composed of non-canonical interactions, are essential for the final shape of the molecule enabling its multiple functions. Our capacity to predict accurate 3D structures is also limited when it comes to the organization of the large intricate network of interactions that form inside those loops. Results We previously developed the integer programming framework RNAMoIP (RNA Motifs over Integer Programming) to reconcile RNA secondary structure and local 3D motif information available in databases. We further develop our model to now simultaneously predict the canonical base pairs (with pseudoknots) from base pair probability matrices with or without alignment. We benchmarked our new method over the all non-redundant RNAs below 150 nucleotides. We show that the joined prediction of canonical base pairs structure and local conserved motifs (i) improves the ratio of well-predicted interactions in the secondary structure, (ii) predicts well canonical and Wobble pairs at the location where motifs are inserted, (iii) is greatly improved with evolutionary information and (iv) non-canonical motifs at kink-turn locations. Availability The source code of the framework is available at https://gitlab.info.uqam.ca/cbe/RNAMoIP and an interactive web server at https://rnamoip.cbe.uqam.ca/