Muscle5: High-accuracy alignment ensembles enable unbiased assessments of sequence homology and phylogeny

🤖 Plain-English Summary

Multiple sequence alignments are widely used to infer evolutionary relationships, enabling inferences of structure, function, and phylogeny. Applied to the phylogeny of RNA viruses, ensemble analysis shows that recently adopted taxonomic phyla are probably polyphyletic.

🔑 Key Findings

• Standard practice is to construct one alignment by some preferred method and use it in further analysis; however, undetected alignment bias can be problematic.
• I describe Muscle5, a novel algorithm which constructs an ensemble of high-accuracy alignment with diverse biases by perturbing a hidden Markov model and permuting its guide tree.
• Confidence in an inference is assessed as the fraction of the ensemble which supports it.

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