Model organisms and new tools: choose your weapons wisely.
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Animals↗
Biomedical subjects
David J Ecker
Publications and source records attributed to David J Ecker.
Discovery of RNA structural elements using evolutionary computation.
RNA molecules fold into characteristic secondary and tertiary structures that account for their diverse functional activities. Many of these RNA structures, or certain structural motifs within them, are thought to recur in multiple genes within a single organism or across the same gene in several organisms and provide a common regulatory mechanism. Search algorithms, such as RNAMotif, can be used to mine nucleotide sequence databases for these repeating motifs. RNAMotif allows users to capture essential features of known structures in detailed descriptors and can be used to identify, with high specificity, other similar motifs within the nucleotide database. However, when the descriptor constraints are relaxed to provide more flexibility, or when there is very little a priori information about hypothesized RNA structures, the number of motif 'hits' may become very large. Exhaustive methods to search for similar RNA structures over these large search spaces are likely to be computationally intractable. Here we describe a powerful new algorithm based on evolutionary computation to solve this problem. A series of experiments using ferritin IRE and SRP RNA stem-loop motifs were used to verify the method. We demonstrate that even when searching extremely large search spaces, of the order of 10(23) potential solutions, we could find the correct solution in a fraction of the time it would have taken for exhaustive comparisons.
Algorithms↗
Rev response elements (RRE) in lentiviruses: an RNAMotif algorithm-based strategy for RRE prediction.
Lentiviruses (a sub-family of the retroviridae family) include primate and non-primate viruses associated with chronic diseases of the immune system and the central nervous system. All lentiviruses encode a regulatory protein Rev that is essential for post-transcriptional transport of the unspliced and incompletely spliced viral mRNAs from nuclei to cytoplasm. The Rev protein acts via binding to an RNA structural element known as the Rev responsive element (RRE). The RRE location and structure and the mechanism of the Rev-RRE interaction in primate and non-primate lentiviruses have been analyzed and compared. Based on structural data available for RRE of HIV-1, a two step computational strategy for prediction of putative RRE regions in lentivirus genomes has been developed. First, the RNAMotif algorithm was used to search genomic sequence for highly structured regions (HSR). Then the program RNAstructure, version 3.6 was used to calculate the structure and thermodynamic stability of the region of approximately 350 nucleotides encompassing the HSR. Our strategy correctly predicted the locations of all previously reported lentivirus RREs. We were able also to predict the locations and structures of potential RREs in four additional lentiviruses.
Algorithms↗