PhyloRNAalifold

PhyloRNAalifold predicts consensus RNA secondary structures from multiple sequence alignments by integrating phylogenetically informed covariation into covariance scoring.

Key Features:

• Consensus structure prediction: Predicts consensus RNA secondary structures from aligned RNA sequences.
• Phylogenetic covariation scoring: Incorporates the number of covarying mutations observed on the phylogenetic tree into covariance scores.
• Thermodynamic folding foundation: Builds on RNAalifold's thermodynamic model to fold aligned RNA sequences.
• Column-wise covariance evaluation: Evaluates conserved signals between two aligned columns for covariance assessment.
• Integration of stability and evolution: Combines thermodynamic stability and evolutionary relationships in a refined scoring scheme.
• Improved covariance metric: Produces covariance scores that have been shown to outperform mutual information in scoring covariance.
• Benchmark-supported improvements: Demonstrates enhanced performance in consensus structure folding in benchmarking comparisons.
• Alignment-dependence: Performance is correlated with alignment characteristics such as pairwise identity and number of sequences in the alignment.

Scientific Applications:

• Consensus RNA secondary structure inference: Infers conserved secondary structures from multiple sequence alignments.
• Detection of covarying base pairs: Identifies base-pair covariation while accounting for phylogenetic history.
• Comparative analysis of RNA evolution: Enables study of evolutionary dynamics of RNA structure across related sequences.

Methodology:

Combines RNAalifold thermodynamic folding of alignments with a refined covariance scoring that counts covarying mutations on the phylogenetic tree and evaluates conserved signals between aligned columns, thereby integrating thermodynamic stability and phylogenetic information.