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Pairwise Local Alignment of Protein Interaction Networks Guided by Models of Evolution

机译:通过演化模型引导的蛋白质交互网络的成对局部对准

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With ever increasing amount of available data on protein-protein interaction (PPI) networks and research revealing that these networks evolve at a modular level, discovery of conserved patterns in these networks becomes an important problem. Recent algorithms on aligning PPI networks target simplified structures such as conserved pathways to render these problems computationally tractable. However, since conserved structures that are parts of functional modules and protein complexes generally correspond to dense subnets of the network, algorithms that are able to extract conserved patterns in terms of general graphs are necessary. With this motivation, we focus here on discovering protein sets that induce subnets that are highly conserved in the interactome of a pair of species. For this purpose, we develop a framework that formally defines the pairwise local alignment problem for PPI networks, models the problem as a graph optimization problem, and presents fast algorithms for this problem. In order to capture the underlying biological processes correctly, we base our framework on duplication/divergence models that focus on understanding the evolution of PPI networks. Experimental results from an implementation of the proposed framework show thatour algorithm is able to discover conserved interaction patterns very effectively (in terms of accuracies and computational cost). While we focus on pairwise local alignment of PPI networks in this paper, the proposed algorithm can be easily adapted tofinding matches for a subnet query in a database of PPI networks.
机译:随着蛋白质 - 蛋白质相互作用(PPI)网络和研究的越来越多的可用数据,揭示这些网络在模块化水平上发展,这些网络中的保守模式的发现成为一个重要问题。最近的算法对准PPI网络的目标简化结构,例如保守的途径,以使这些问题进行计算易行。然而,由于作为功能性模块和蛋白质复合物的部分的保守结构通常对应于网络的密集子网,所以需要在一般图表中提取保守模式的算法。通过这种动机,我们在这里专注于发现蛋白群,诱导在一对物种的互联蛋白酶中高度保守的子网。为此目的,我们开发了一个框架,该框架是正式定义PPI网络的成对本地对准问题,将问题模拟为图形优化问题,并为此问题提供了快速算法。为了正确捕获潜在的生物过程,我们将我们的框架基于重复/发散模型,专注于理解PPI网络的演变。所提出的框架实施的实验结果表明,大家算法能够非常有效地发现保守的相互作用模式(在准确性和计算成本方面)。虽然我们专注于PPI网络的成对局部对准,但是所提出的算法可以很容易地适应PPI网络数据库中的子网查询的TOFINDING匹配。

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