Functional cartography of complex metabolic networks

Abstract

High-throughput techniques are leading to an explosive growth in the size of biological databases and creating the opportunity to revolutionize our understanding of life and disease. Interpretation of these data remains, however, a major scientific challenge. Here, we propose a methodology that enables us to extract and display information contained in complex networks. Specifically, we demonstrate that one can (i) find functional modules in complex networks, and (ii) classify nodes into universal roles according to their pattern of intra- and inter-module connections. The method thus yields a ``cartographic representation'' of complex networks. Metabolic networks are among the most challenging biological networks and, arguably, the ones with more potential for immediate applicability. We use our method to analyze the metabolic networks of twelve organisms from three different super-kingdoms. We find that, typically, 80% of the nodes are only connected to other nodes within their respective modules, and that nodes with different roles are affected by different evolutionary constraints and pressures. Remarkably, we find that low-degree metabolites that connect different modules are more conserved than hubs whose links are mostly within a single module.