Comparative Analysis of Topological Patterns in Different Mammalian Networks

Abstract

We have systematically analyzed various topological patterns comprising 1, 2 or 3 nodes in the mammalian metabolic, signal transduction and transcription networks: These patterns were analyzed with regard to their frequency and statistical over-representation in each network, as well as to their topological significance for the coherence of the networks. The latter property was evaluated using the pairwise disconnectivity index, which we have recently introduced to quantify how critical network components are for the internal connectedness of a network. The 1-node pattern made up by a vertex with a self-loop has been found to exert particular properties in all three networks. In general, vertices with a self-loop tend to be topologically more important than other vertices. Moreover, self-loops have been found to be attached to most 2-node and 3-node patterns, thereby emphasizing a particular role of self-loop components in the architectural organization of the networks. For none of the networks, a positive correlation between the mean topological significance and the Z-score of a pattern could be observed. That is, in general, motifs are not per se more important for the overall network coherence than patterns that are not over-represented. All 2-and 3-node patterns that are over-represented and thus qualified as motifs in all three networks exhibit a loop structure. This intriguing observation can be viewed as an advantage of loop-like structures in building up the regulatory circuits of the whole cell. The transcription network has been found to differ from the other networks in that (i) self-loops play an even higher role, (ii) its binary loops are highly enriched with self-loops attached, and (iii) feedback loops are not over-represented. Metabolic networks reveal some particular topological properties which may reflect the fact that metabolic paths are, to a large extent, reversible. Interestingly, some of the most important 3-node patterns of both the transcription and the signaling network can be concatenated to subnetworks comprising many genes that play a particular role in the regulation of cell proliferation.

Integration of gene expression data with prior knowledge for network analysis and validation

“…Substrates such as ATP or water taking part in more than 100 reactions were discarded. This is the gene-family equivalent to the network extraction method presented and used in [ 19 ]. The metabolic reference network is included in Additional File 1 .…”