Gene finding for the helical cytokines

Abstract

Gene finding remains an open problem well after the sequencing of the human genome. The low gene sensitivity of current methods is a problem for divergent protein families, because fairly accurate exon assemblies are required before sensitive fold recognition algorithms can be applied. This paper presents a new genomic threading algorithm which integrates the gene finding and fold recognition steps into a single process. The method is applicable to evolutionarily divergent protein families that have retained some trace of their common ancestry, number and phase of introns, sizes of exons and placement of structural elements on specific exons. Such conserved structural signals may be visible despite dramatic evolution of protein sequence. The method is evaluated on the family of helical cytokines by cross-validation sensitivity analysis. The method has also been applied to all intergenic regions of the human genome, and an expression and cloning approach has been coupled with the predictions of the method. Two genes discovered by this method are discussed. All data used and the results obtained in the cross-validation analysis are available at http://www.soi.city.ac.uk/~conklin/papers/GT/