Departament Ciències Mèdiques Bàsiques, Universitat de Lleida & IRBLleida, Lleida, Spain.
PLoS One. 2011 Feb 2;6(2):e16015. doi: 10.1371/journal.pone.0016015.
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. 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 FINDINGS: In 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/SIGNIFICANCE: The 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.
模型生物被用于研究,是因为它们提供了一个框架,可以在此基础上开发和优化方法,从而促进和标准化分析。这些生物应该能够代表它们所代理的生物。然而,在实践中,模型生物通常是根据特定的需要选择的,而不考虑其代表性,因为在选择过程中包含这一考虑的系统和理性的方法仍然缺乏。
方法/主要发现:在这项工作中,我们提出了这样一种方法,并将其应用于酿酒酵母作为模型生物的优势和局限性的初步研究中。该方法依赖于蛋白质功能分类为不同的生物途径和过程,以及在假定的模型生物和我们希望外推结果的其他生物之间进行全蛋白质组比较。在这里,我们将酿酒酵母与来自不同门的 704 种其他生物进行了比较。对于每种生物,我们的结果确定了酿酒酵母可用于外推的途径和过程。我们发现,一般来说,动物,特别是智人,是酿酒酵母可能是研究许多共同生物过程的良好模型的非真菌生物之一。我们通过正确预测哪些生物在几个不同的生物过程中表型上与酿酒酵母的差异更大,验证了我们的方法。
结论/意义:我们提出的方法可以用于选择其他物种中研究生物过程的适当替代模型生物,这些生物更难研究。例如,可以确定适当的模型来研究人类的病理学或具有较长发育时间的物种(如植物)中的特定生物学过程。