KnotInFrame: prediction of -1 ribosomal frameshift events

Theis, Corinna; Reeder, Jens; Giegerich, Robert

Apparently, the method presented here and the one by Jacobs et al. differ substantially in their results. Various reasons have been given above, e.g. the differences in the structure prediction methods. However, we think the most influencing difference in both methods is the scoring system. While KnotInFrame employs normalized dominance, Jacobs et al. use z-scores and free energy for ranking. The fact that these two criteria are not equivalent can already be concluded from Figure 4 , but has also been proven by our yeast screen comparison. In our opinion, normalized dominance is better suited for the task of discriminating true PRF signals from random ones. The z-score measures the evolutionary fitness of a sequence under evaluation against other (random) sequences that could have evolved instead, but were rejected during evolution due to an inferior fitness. In contrast, the normalized dominance makes an exact statement of how likely a given sequence folds into a frameshift inducing structure and not into an alternative one. In this sense, normalized dominance evaluates the 'fitness' of the PRF structure against its present competitors-those which exist in the folding space of the given RNA sequence, rather than against those that might exist in the past/future of a mutated sequence.