Discovery and analysis of biochemical subnetwork hierarchies.pdf

a r X i v : q - b i o / 0 3 0 9 0 1 1 v 2 [ q - b i o .M N ] 3 0 S e p 2 0 0 3 Discovery and analysis of biochemical subnetwork hierarchies Petter Holme Department of Physics, Ume? University 901 87 Ume?, Sweden Mikael Huss SANS, NADA, Royal Institute of Technology 100 44 Stockholm, Sweden Abstract The representation of a biochemical network as a graph is the coarsest level of description in cellular biochemistry. By studying the network structure one can draw conclusions on the large scale organisation of the biochemical processes. We describe methods how one can extract hierarchies of subnetworks, how these can be interpreted and further deconstructed to find autonomous subnetworks. The large- scale organisation we find is characterised by a tightly connected core surrounded by increasingly loosely connected substrates. 1 Introduction At the coarsest level of description, cellular biochemistry can be repre- sented as a network of vertices (substrates) linked by chemical reactions. For both conceptual and analytical purposes, the vastness and complexity of these biochemical networks calls for a division into smaller subunits. This is nothing new—traditionally biochemists have talked about func- tional subnetworks, the citric acid cycle being one example, comprised of biochemical pathways. As modern day genomics gives an increasingly 2 Holme Huss Biochemical subnetwork hierarchies comprehensive picture of the biochemical network one would like to com- plement the traditional way of mapping out subnetworks by objective graph theoretical methods. By such methods we can address not only the question what relevant subnetworks there are, but also the hierarchical or- ganisation of subnetworks (can subnetworks be said to consist of smaller subnetworks, and so on), and also more fundamental questions about in what context the subnetwork concept is relevant andwhen the biochemical circuitry is to be considered as a functional whole. The graph-theoretical signature