Remote homology search with hidden Potts models
Fig 2
Importance sampling alignment algorithm schematic.
Toy example of aligning an RNA sequence CUCUGGAAG to models of its sequence/structure consensus, where the true structural alignment has two nested base pairs (brackets in structure line) and one pseudoknot (‘Aa’). Suboptimal alignments of the sequence are sampled probabilistically using a pHMM. A pHMM does not capture residue correlations due to base-pairing, so only some proposed alignments satisfy the expected consensus nested (cyan) or pseudoknotted (pink) base pairs. The proposed alignments are re-scored and re-ranked under the HPM, which does capture correlation structure; the correct alignment with the highest probability under the HPM is identified (green), and the sequence’s total probability is obtained by importance-weighted summation over the sampled alignments.