Abstract
MOTIVATION: RNA structure is essential for the function of many non-coding RNAs. Using multiple homologous sequences, which share structure and function, secondary structure can be predicted with much higher accuracy than with a single sequence. It can be difficult, however, to establish a set of homologous sequences when their structure is not yet known. We developed a method to identify sequences in a set of putative homologs that are in fact non-homologs. RESULTS: Previously, we developed TurboFold to estimate conserved structure using multiple, unaligned RNA homologs. Here, we report that the positive predictive value of TurboFold is significantly reduced by the presence of contamination by non-homologous sequences, although the reduction is less than 1%. We developed a method called DecoyFinder, which applies machine learning trained with features determined by TurboFold, to detect sequences that are not homologous with the other sequences in the set. This method can identify approximately 45% of non-homologous sequences, at a rate of 5% misidentification of true homologous sequences. AVAILABILITY: DecoyFinder and TurboFold are incorporated in RNAstructure, which is provided for free and open source under the GPL V2 license. It can be downloaded at http://rna.urmc.rochester.edu/RNAstructure.html.