Abstract
BackgroundModel organisms are used for research because they provide a framework on which to develop and optimize methods that facilitate and standardize analysis. Such organisms should be representative of the living beings for which they are to serve as proxy. However, in practice, a model organism is often selected ad hoc, and without considering its representativeness, because a systematic and rational method to include this consideration in the selection process is still lacking.Methodology/Principal FindingsIn this work we propose such a method and apply it in a pilot study of strengths and limitations of Saccharomyces cerevisiae as a model organism. The method relies on the functional classification of proteins into different biological pathways and processes and on full proteome comparisons between the putative model organism and other organisms for which we would like to extrapolate results. Here we compare S. cerevisiae to 704 other organisms from various phyla. For each organism, our results identify the pathways and processes for which S. cerevisiae is predicted to be a good model to extrapolate from. We find that animals in general and Homo sapiens in particular are some of the non-fungal organisms for which S. cerevisiae is likely to be a good model in which to study a significant fraction of common biological processes. We validate our approach by correctly predicting which organisms are phenotypically more distant from S. cerevisiae with respect to several different biological processes.Conclusions/SignificanceThe method we propose could be used to choose appropriate substitute model organisms for the study of biological processes in other species that are harder to study. For example, one could identify appropriate models to study either pathologies in humans or specific biological processes in species with a long development time, such as plants.
Highlights
The use of model organisms for research is a hallmark of scientific endeavor (e.g. [1,2,3,4,5,6,7])
We use: a) The Gene Ontology (GO) [22], which has been widely used for annotating function and localization of genes at a coarse level in many organisms [23,24,25,26,27], and b) The pathways that regulate and execute the processes that one is interested in studying, as defined in KEGG [28]
Functional comparison of biological processes and pathways between S. cerevisiae and other organisms. After getting such a bird’s eye view of the similarities and differences between S. cerevisiae and different clades of organisms with respect to different biological processes, we focus on individual organisms
Summary
The use of model organisms for research is a hallmark of scientific endeavor (e.g. [1,2,3,4,5,6,7]). A gap exists in systematically establishing how close different organisms are with respect to a given process, before choosing one of them as a model for studying that process. Such a choice should be informed by several considerations. Model organisms are used for research because they provide a framework on which to develop and optimize methods that facilitate and standardize analysis Such organisms should be representative of the living beings for which they are to serve as proxy. In practice, a model organism is often selected ad hoc, and without considering its representativeness, because a systematic and rational method to include this consideration in the selection process is still lacking
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