Letters to Nature

Nature 433, 895-900 (24 February 2005) | doi:10.1038/nature03288; Received 17 August 2004; Accepted 16 December 2004

Functional cartography of complex metabolic networks

Roger Guimerà1 & Luís A. Nunes Amaral1

  1. NICO and Department of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois 60208, USA

Correspondence to: Luís A. Nunes Amaral1 Correspondence and requests for materials should be addressed to L.A.N.A. (Email: amaral@northwestern.edu).

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 networks1, 2, 3. Specifically, we demonstrate that we can find functional modules4, 5 in complex networks, and 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 networks6, 7, 8 are among the most challenging biological networks and, arguably, the ones with most potential for immediate applicability9. We use our method to analyse the metabolic networks of twelve organisms from three different superkingdoms. 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 metabolites that participate in only a few reactions but that connect different modules are more conserved than hubs whose links are mostly within a single module.

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