Systematic Bioinformatic Discovery of 'Hidden' Virus Genes. (360G-Wellcome-088789_Z_09_Z)
This proposal concerns the bioinformatic discovery of genes that have been persistently overlooked in important RNA viruses. Typically such genes are short, overlapping, and/or translated via non-canonical mechanisms. Using my own software packages developed for finding (a) short overlapping genes, and (b) phylogenetically conserved signals for ribosomal frameshifting, I recently identified a number of new virus genes, most significantly short overlapping genes in both the potyviruses and the alphaviruses, both apparently translated as frameshift fusion proteins (Chung et al 2008, Firth et al 2008e). The goal of the proposed research is to create a much larger alignment database by using all relevant RNA virus sequences in GenBank; analyze the alignments using a variety of techniques to systematically identify new 'hidden' genes; and develop additional software packages for virus genome analysis. In addition, I will develop public web-interfaces to key programs and databases develo ped during the fellowship, and extend certain analyses to DNA viruses. A selection of bioinformatic predictions will be experimentally tested in order to establish confidence in the prediction algorithms, stimulate further experimental follow-up by other virologists, and to characterize new stimulatory signals associated with non-canonical translation mechanisms as input for further bioinformatic searches.
£550,205 23 Jun 2009