Using Sub-Network Combinations to Scale Up an Enumeration Method for Determining the Network Structures of Biological Functions.
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ABSTRACT: Deduction of biological regulatory networks from their functions is one of the focus areas of systems biology. Among the different techniques used in this reverse-engineering task, one powerful method is to enumerate all candidate network structures to find suitable ones. However, this method is severely limited by calculation capability: due to the brute-force approach, it is infeasible for networks with large number of nodes to be studied using traditional enumeration method because of the combinatorial explosion. In this study, we propose a new reverse-engineering technique based on the enumerating method: sub-network combinations. First, a complex biological function is divided into several sub-functions. Next, the three-node-network enumerating method is applied to search for sub-networks that are able to realize each of the sub-functions. Finally, complex whole networks are constructed by enumerating all possible combinations of sub-networks. The optimal ones are selected and analyzed. To demonstrate the effectiveness of this new method, we used it to deduct the network structures of a Pavlovian-like function. The whole Pavlovian-like network was successfully constructed by combining robust sub-networks, and the results were analyzed. With sub-network combination, the complexity has been largely reduced. Our method also provides a functional modular view of biological systems.
SUBMITTER: Xi JY
PROVIDER: S-EPMC5161363 | biostudies-other | 2016
REPOSITORIES: biostudies-other
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