Network-Based Structural Alignment of RNA Sequences Using TOPAS.

Abstract

TOPAS (TOPological network-based Alignment of Structural RNAs) is a network-based alignment algorithm that predicts structurally sound pairwise alignment of RNAs. In order to take advantage of recent advances in comparative network analysis for efficient structurally sound RNA alignment, TOPAS constructs topological network representations for RNAs, which consist of sequential edges connecting nucleotide bases as well as structural edges reflecting the underlying folding structure. Structural edges are weighted by the estimated base-pairing probabilities. Next, the constructed networks are aligned using probabilistic network alignment techniques, which yield a structurally sound RNA alignment that considers both the sequence similarity and the structural similarity between the given RNAs. Compared to traditional Sankoff-style algorithms, this network-based alignment scheme leads to a significant reduction in the overall computational cost while yielding favorable alignment results. Another important benefit is its capability to handle arbitrary folding structures, which can potentially lead to more accurate alignment for RNAs with pseudoknots.