Evaluating Distance Measures for RNA Motif Search

This paper extends an earlier study which outlined a bioinformatic pipeline for exploratory search for RNA motifs incorporating both primary and secondary structure. The pipeline is applied to three data sets, one of which is a larger version of that used in the earlier study. Instead of a single method of estimating the distance between RNA folds four distance measures were tested. The data sets are: a set of random control sequences, a set of synthetic sequences with simple designed folds, and the iron response element data set for which actual biological RNA folds are available. The pipeline demonstrates the ability to produce clusters that contain known motifs in the biological data and those designed into the synthetic data. The results for the distance measures varies substantially and one of the measures, difference in energy, is found to be too simplistic to be useful for differentiating motifs. The other three distance measures all demonstrate some degree of merit. At the heart of the pipeline is a non-linear projection algorithm that uses evolutionary computation to display the intra-RNA-fold distances so that the various distance measures can be visually compared. While the performance of this algorithm is acceptable, suggestions for improving it are made.