基于蛋白质-蛋白质功能关联网络光谱聚类的细菌模块检测

Hongwei Wu, Yaming Lin, Fun Choi Chan, R. Alba-Flores
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引用次数: 1

摘要

基于网络分析的模块检测在许多领域具有重要意义。在细胞/分子生物学中,基于代谢/调控网络分析的模块检测不仅有助于我们更多地了解生物体细胞机制的功能和进化,而且还将为潜在的药物靶点提供可处理的上下文信息,并促进药物设计的改进。本文提出了基于蛋白质-蛋白质功能关联网络光谱聚类的细菌模块检测方法的初步研究。我们首先研究了谱聚类算法的参数(即聚类数量)如何影响我们的模块检测结果,并证明当聚类数量设置得太小或太大时,所得到的模块收集在基因覆盖和模块内关联方面会恶化。然后,我们将我们的预测模块与随机生成的模块进行了比较,并证明我们的模块(i)具有更高的模块内与模块间基因-基因功能关联评分比例,并且(ii)可以更好地捕获实验验证模块中固有的模块化信息。最后,我们比较了7种细菌的模块集合,并观察到与膜运输和细胞运动相关的模块在多种生物中是保守的。由于从科学和技术的角度来看,研究不同分辨率的功能模块是可取的,我们认为频谱聚类算法具有不同参数设置所带来的灵活性,在捕获网络的模块化特性和计算负担能力方面提供了合适的解决方案。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Module detection for bacteria based on spectral clustering of protein-protein functional association networks
Network analysis-based module detection has significant implications in many fields. In cellular/ molecular biology, module detection based on analyses of metabolic/regulatory networks will not only help us understand more about the function and evolution of cellular machinery of an organism, but will also provide tractable contextual information for potential drug targets and facilitate improvements in drug designs. We here present our preliminary study on the module detection for bacteria based on the spectral clustering of the protein-protein functional association networks. We first examined how the parameter of the spectral clustering algorithm (i.e., the number of clusters) affects our module detection results, and demonstrated that when the number of clusters was set too small or too large the resulting module collection deteriorate in terms of gene coverage and intra-module association. We then compared our predicted modules against the randomly generated modules, and demonstrated that our modules (i) have a higher ratio of the intra-module to inter-module gene-gene functional association scores and (ii) can better capture the modularization information inherent in the experimentally verified modules. Finally we compared the module collections of seven bacterial organisms, and observed that modules related to membrane transport and cell motility are among those that are conserved among multiple organisms. Because it is desirable from both scientific and technical points of view to study functional modules at various resolution levels, we believe that the spectral clustering algorithm, with the flexibility rendered by different parameter settings, provides an appropriate solution in terms of capturing the modularization properties of networks and computational affordability.
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