Extraction of phylogenetic network modules from the metabolic network

We extracted such "common" sub-networks, defined as "phylogenetic network modules," using phylogenetic profiles and cluster analysis. The enzymes in the same "phylogenetic network module" have similar phylogenetic profiles and related functions. These modules are shown to be phylogenetic building blocks. Furthermore, the network of the modules illustrated hierarchical feature as well as the network of enzymes involved in the metabolism.We conclude that phylogenetic network modules are evolutionary conserved functional units in the metabolic network. We claim that our concept of phylogenetic modules provides a more accurate understanding of the evolution of biological networks.Bio-systems are constructed by various relationships between genes, compounds and proteins. These elements are intertwined, thus forming a complex network. Such genetic or physical associations contribute to the complicated cellular functions.In order to characterize whole networks or to find unknown interactions between elements (gene/compound/protein), many research groups have applied the integration of qualitatively different interactions. For example, Rison et al attempted to find unknown functions of genes using genome location, sequence similarity, and relative position in the metabolic network [1], and Yamanishi et al similarly attempted to apply a kernel method [2]. Such integrative methods infer common features and new categories of genes. Classically, such new categories were determined manually using expert knowledge. The KEGG metabolic pathway [3] is one such example. On the other hand, recent studies have attempted to define new categories automatically using comprehensive data sets such as microarray data and metabolic networks [4]. Such analyses can classify elements by globally assessing many relationships. Many research groups advocate various functional categories of genes and proteins, such as transcriptional clusters [5,6], protein complexes [7], metabolic network [3,8], an