A Method for RNA Structure Prediction Shows Evidence for Structure in lncRNAs

To compare the secondary structure profiles of RNA molecules we developed the CROSSalign method. CROSSalign is based on the combination of the Computational Recognition Of Secondary Structure (CROSS) algorithm to predict the RNA secondary structure profile at single-nucleotide resolution using sequence information and the Dynamic Time Warping (DTW) method to align profiles of different lengths. We applied CROSSalign to investigate the structural conservation of long non-coding RNAs such as XIST and HOTAIR as well as ssRNA viruses including HIV. In a pool of sequences with the same secondary structure CROSSalign accurately recognizes repeat A of XIST and domain D2 of HOTAIR and outperforms other methods based on covariance modelling. CROSSalign can be applied to perform pair-wise comparisons and is able to find homologues between thousands of matches identifying the exact regions of similarity between profiles of different lengths. The algorithm is freely available at the webpage http://service.tartaglialab.com//new_submission/crossalign.