The information criterion of minimum message length (MML) provides a powerful statistical framework for inductive reasoning from observed data. We apply MML to the problem of protein sequence comparison using finite state models with Dirichlet distributions. The resulting framework allows us to supersede the ad hoc cost functions commonly used in the field, by systematically addressing the problem of arbitrariness in alignment parameters, and the disconnect between substitution scores and gap costs. Furthermore, our framework enables the generation of marginal probability landscapes over all possible alignment hypotheses, with potential to facilitate the users to simultaneously rationalize and assess competing alignment relationships between protein sequences, beyond simply reporting a single (best) alignment. We demonstrate the performance of our program on benchmarks containing distantly related protein sequences.
Sumanaweera, D., Allison, L., & Konagurthu, A. (2019). Statistical compression of protein sequences and inference of marginal probability landscapes over competing alignments using finite state models and Dirichlet priors. Bioinformatics, 35(14), i360-i369. [btz368]. https://doi.org/10.1093/bioinformatics/btz368