Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, Karnataka, India.
Int J Biol Macromol. 2011 May 1;48(4):613-9. doi: 10.1016/j.ijbiomac.2011.01.030. Epub 2011 Feb 16.
Molecular understanding of disease processes can be accelerated if all interactions between the host and pathogen are known. The unavailability of experimental methods for large-scale detection of interactions across host and pathogen organisms hinders this process. Here we apply a simple method to predict protein-protein interactions across a host and pathogen organisms. We use homology detection approaches against the protein-protein interaction databases, DIP and iPfam in order to predict interacting proteins in a host-pathogen pair. In the present work, we first applied this approach to the test cases involving the pairs phage T4 -Escherichia coli and phage lambda -E. coli and show that previously known interactions could be recognized using our approach. We further apply this approach to predict interactions between human and three pathogens E. coli, Salmonella enterica typhimurium and Yersinia pestis. We identified several novel interactions involving proteins of host or pathogen that could be thought of as highly relevant to the disease process. Serendipitously, many interactions involve hypothetical proteins of yet unknown function. Hypothetical proteins are predicted from computational analysis of genome sequences with no laboratory analysis on their functions yet available. The predicted interactions involving such proteins could provide hints to their functions.
如果已知宿主和病原体之间的所有相互作用,就可以加速对疾病过程的分子理解。但是,缺乏用于大规模检测宿主和病原体生物之间相互作用的实验方法,这阻碍了这一进程。在这里,我们应用一种简单的方法来预测宿主和病原体生物之间的蛋白质-蛋白质相互作用。我们使用同源检测方法针对蛋白质-蛋白质相互作用数据库 DIP 和 iPfam,以预测宿主-病原体对中的相互作用蛋白。在本工作中,我们首先将该方法应用于涉及噬菌体 T4-Escherichia coli 和噬菌体 lambda-E. coli 对的测试案例,并表明可以使用我们的方法识别先前已知的相互作用。我们进一步将该方法应用于预测人类与三种病原体大肠杆菌、鼠伤寒沙门氏菌和鼠疫耶尔森菌之间的相互作用。我们鉴定了一些涉及宿主或病原体蛋白的新相互作用,这些相互作用可以被认为与疾病过程高度相关。偶然的是,许多相互作用涉及尚未确定功能的假设蛋白。假设蛋白是根据基因组序列的计算分析预测的,而对其功能的实验室分析尚未进行。涉及此类蛋白质的预测相互作用可能为其功能提供线索。