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Systematic planning of genome-scale experiments in poorly studied species.

ABSTRACT: Genome-scale datasets have been used extensively in model organisms to screen for specific candidates or to predict functions for uncharacterized genes. However, despite the availability of extensive knowledge in model organisms, the planning of genome-scale experiments in poorly studied species is still based on the intuition of experts or heuristic trials. We propose that computational and systematic approaches can be applied to drive the experiment planning process in poorly studied species based on available data and knowledge in closely related model organisms. In this paper, we suggest a computational strategy for recommending genome-scale experiments based on their capability to interrogate diverse biological processes to enable protein function assignment. To this end, we use the data-rich functional genomics compendium of the model organism to quantify the accuracy of each dataset in predicting each specific biological process and the overlap in such coverage between different datasets. Our approach uses an optimized combination of these quantifications to recommend an ordered list of experiments for accurately annotating most proteins in the poorly studied related organisms to most biological processes, as well as a set of experiments that target each specific biological process. The effectiveness of this experiment- planning system is demonstrated for two related yeast species: the model organism Saccharomyces cerevisiae and the comparatively poorly studied Saccharomyces bayanus. Our system recommended a set of S. bayanus experiments based on an S. cerevisiae microarray data compendium. In silico evaluations estimate that less than 10% of the experiments could achieve similar functional coverage to the whole microarray compendium. This estimation was confirmed by performing the recommended experiments in S. bayanus, therefore significantly reducing the labor devoted to characterize the poorly studied genome. This experiment-planning framework could readily be adapted to the design of other types of large-scale experiments as well as other groups of organisms.

ORGANISM(S): Saccharomyces cerevisiae Saccharomyces bayanus

PROVIDER: GSE16544 | GEO | 2010/01/24

SECONDARY ACCESSION(S): PRJNA116169

REPOSITORIES: GEO

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Project description:A fundamental problem in biology is the molecular basis for divergence among related organisms. We have investigated the level of divergence of transcription factor binding sites for two key factors that regulate developmental processes in the budding yeasts. The genomic binding locations for the Ste12 and Tec1 transcription factors in S. cerevisiae, S. mikatae and S. bayanus were mapped by chromatin immunoprecipitation combined with microarrays (chIP chip)1, 2 and compared to one another. While there was a large core network which was conserved in all three species, there were many instances of binding events whose relative levels differ significantly quantitatively in one species relative to another and as well as species-specific binding events. One interesting class of genes were identified that were bound only in S. mikatae and S. bayanus; many of these genes are targets of Ste12 in haploid strains of S. cerevisiae, suggesting that S. cerevisiae has uniquely acquired the ability to differentially regulate these genes in haploid and diploid cells in these species. To extend these studies, the transcriptional network for the Ste12 homologue (Cph1) in Candida albicans was also mapped and compared to the Saccharomyces species. Again, there were several genes bound by Cph1 which are involved in mating in S. cerevisiae, suggesting that the precise delineation between many mating and pseudohyphal targets by Ste12 may be specific to S. cerevisiae. Overall our results demonstrate that transcription binding sites differ faster than gene content indicating that gene regulation at the level of transcription factor binding is likely to be a major mode of evolutionary divergence between related species. We expect that this divergence is essential for the distinct ecological niches inhabited by these organisms. Keywords: chIP-chip ChIP-chip was performed on Ste12 and Tec1 from S. cerevisiae, S. mikatae and S. bayanus in addition to Cph1 from S. cerevisiae. Three biological replicates were performed for each factor in each species with one replicate representing a dye swap.

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Systematic planning of genome-scale experiments in poorly studied species.

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