A rational in silico and experimental approach to mapping interactomes applied to Candida glabrata

应用于光滑念珠菌的相互作用组图谱的理性计算机和实验方法

• 批准号: BB/F013337/1
• 负责人: Simon Lovell
• 金额: $ 43.31万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF013337%2F1
• 关键词: rational; silico; experimental; approach; mapping

Protein interaction networks have become important tools in the understanding of molecular phenotypes of biological model organisms. Although there are well known problems regarding the quality and completeness of protein-interaction data, a constantly growing amount of such data is being assembled. This data is primarily derived from a few well characterized model organisms, notably Saccharomyces cerevisiae. For other biological important organisms data is sparse. Experimental mapping of interactomes is labour intensive and expensive, resulting in a dearth of interaction data in the vast majority of organisms, including humans. A number of computational approaches have been proposed which use homology to predict protein interactions across species. These approaches cannot, however, predict differences between different organisms. Because of their underlying assumptions about homology, at best they are restricted to establishing a scaffold of protein-protein interactions that are universally shared. Here we will develop novel tools that overcome this severe limitation. These tools will allow us to predict reliably and comprehensively protein interaction data using sophisticated bioinformatics, statistical and comparative arguments. These will be applied to, and validated in, the pathogentic fungus Candida glabrata, one of the most important fungal pathogens of humans. The new approaches will be integrated into a coherent framework for the rational mapping of interactomes. Our approach will differ from and improve upon existing approaches by exploring a range of different statistical models and classifiers and through the close integration between dry and wet approaches. We will furthermore establish an experimentally derived scaffold for protein interactions which can be used to guide as well as validate the theoretical predictors. This joint in-silico and experimental study will develop a general, rational approach to mapping interactomes, especially in organisms that are reasonably closely related to well studied model organisms (e.g. Anopheles gambiae and Aedes aegypti from Drosophila melanogaster; or Caenorhabditis briggsae from Caenorhabditis elegans). We will furthermore explore the added benefit of this type of network data for functional and evolutionary analyses. In addition to developing C.glabrata as a model organism for comparative systems biology, this approach will further highlight the role of comparative approaches in integrative systems biology.

蛋白质相互作用网络已成为理解生物模式生物分子表型的重要工具。尽管众所周知，蛋白质相互作用数据的质量和完整性存在问题，但正在收集的此类数据数量不断增加。这些数据主要来自于几个充分表征的模式生物，特别是酿酒酵母。关于其他重要生物体的数据很少。相互作用组的实验作图是劳动密集型的且昂贵的，导致包括人类在内的绝大多数生物体中缺乏相互作用数据。已经提出了许多计算方法，其使用同源性来预测跨物种的蛋白质相互作用。然而，这些方法不能预测不同生物体之间的差异。由于它们对同源性的基本假设，它们充其量仅限于建立普遍共享的蛋白质-蛋白质相互作用的支架。在这里，我们将开发新的工具来克服这个严重的限制。这些工具将使我们能够使用复杂的生物信息学，统计和比较参数来可靠和全面地预测蛋白质相互作用数据。这些将被应用于，并验证，致病真菌光滑念珠菌，人类最重要的真菌病原体之一。新的方法将被整合到一个连贯的框架，合理映射的相互作用。我们的方法将通过探索一系列不同的统计模型和分类器，并通过干方法和湿方法之间的紧密结合，与现有的方法不同，并对现有的方法进行改进。我们将进一步建立一个实验衍生的蛋白质相互作用的支架，可以用来指导以及验证理论预测。这种联合的计算机模拟和实验研究将开发一种通用的，合理的方法来映射相互作用组，特别是在与研究良好的模式生物（例如，冈比亚按蚊和埃及伊蚊从果蝇;或Caushabditis briggsae从秀丽隐杆线虫）相当密切相关的生物中。我们将进一步探索这种类型的网络数据对于功能和进化分析的额外好处。除了将光滑念珠菌作为比较系统生物学的模式生物外，这种方法还将进一步突出比较方法在综合系统生物学中的作用。

项目成果

The role of protein interactions in mediating essentiality and synthetic lethality.

蛋白质相互作用在介导本质和合成致死性中的作用。

• DOI: 10.1371/journal.pone.0062866
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Talavera D;Robertson DL;Lovell SC
• 通讯作者: Lovell SC

Characterization of protein-protein interaction interfaces from a single species.

• DOI: 10.1371/journal.pone.0021053
• 发表时间: 2011
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Talavera D;Robertson DL;Lovell SC
• 通讯作者: Lovell SC

Evolvability of yeast protein-protein interaction interfaces.

酵母蛋白质-蛋白质相互作用界面的进化性。

• DOI: 10.1016/j.jmb.2012.03.021
• 发表时间: 2012
• 期刊: Journal of molecular biology
• 影响因子: 5.6
• 作者: Talavera D

Evolution in protein interaction networks: co-evolution, rewiring and the role of duplication.

蛋白质相互作用网络的进化：共同进化、重新布线和复制的作用。

• DOI: 10.1042/bst0370768
• 发表时间: 2009
• 期刊: Biochemical Society transactions
• 影响因子: 3.9
• 作者: Robertson DL

Alternative splicing and protein interaction data sets.

选择性剪接和蛋白质相互作用数据集。

• DOI: 10.1038/nbt.2540
• 发表时间: 2013
• 期刊: Nature biotechnology
• 影响因子: 46.9
• 作者: Talavera D