RNA threading with secondary structure and sequence profile

Abstract

Abstract Motivation RNA threading aims to identify remote homologies for template-based modeling of RNA 3D structure. Existing RNA alignment methods primarily rely on secondary structure alignment. They are often time- and memory-consuming, limiting large-scale applications. In addition, the accuracy is far from satisfactory. Results Using RNA secondary structure and sequence profile, we developed a novel RNA threading algorithm, named RNAthreader. To enhance the alignment process and minimize memory usage, a novel approach has been introduced to simplify RNA secondary structures into compact diagrams. RNAthreader employs a two-step methodology. Initially, integer programming and dynamic programming are combined to create an initial alignment for the simplified diagram. Subsequently, the final alignment is obtained using dynamic programming, taking into account the initial alignment derived from the previous step. The benchmark test on 80 RNAs illustrates that RNAthreader generates more accurate alignments than other methods, especially for RNAs with pseudoknots. Another benchmark, involving 30 RNAs from the RNA-Puzzles experiments, exhibits that the models constructed using RNAthreader templates have a lower average RMSD than those created by alternative methods. Remarkably, RNAthreader takes less than two hours to complete alignments with ∼5000 RNAs, which is 3–40 times faster than other methods. These compelling results suggest that RNAthreader is a promising algorithm for RNA template detection. Availability and implementation https://yanglab.qd.sdu.edu.cn/RNAthreader