RNAmountAlign: efficient software for local, global, semiglobal pairwise and multiple RNA sequence/structure alignment

TL;DR

RNAmountAlign is a fast, efficient software tool for RNA sequence and structure alignment that combines sequence and structural data, providing statistical significance and supporting multiple alignment types with good accuracy.

Contribution

It introduces a cubic-time, memory-efficient RNA alignment algorithm with p-value estimation, outperforming existing heuristic methods in speed while maintaining accuracy.

Findings

Runs in O(n^3) time and O(n^2) space

Provides p-values for local alignments based on Karlin-Altschul statistics

Achieves comparable accuracy with significantly faster performance

Abstract

Alignment of structural RNAs is an important problem with a wide range of applications. Since function is often determined by molecular structure, RNA alignment programs should take into account both sequence and base-pairing information for structural homology identi^Lcation. A number of successful alignment programs are heuristic versions of Sanko^K's optimal algorithm. Most of them require O(n4) run time. This paper describes C++ software, RNAmountAlign, for RNA sequence/structure alignment that runs in O(n3) time and O(n2) space; moreover, our software returns a p-value (transformable to expect value E) based on Karlin-Altschul statistics for local alignment, as well as parameter ^Ltting for local and global alignment. Using incremental mountain height, a representation of structural information computable in cubic time, RNAmountAlign implements quadratic time pairwise local, global and global/semiglobal (query search) alignment using a weighted combination of sequence and structural similarity. RNAmountAlign is capable of performing progressive multiple alignment as well. Benchmarking of RNAmountAlign against LocARNA, LARA, FOLDALIGN, DYNALIGN and STRAL shows that RNAmountAlign has reasonably good accuracy and much faster run time supporting all alignment types.