Motivation: With the growing availability of high-throughput protein– protein interaction (PPI) data, it has become possible to consider how a protein’s local or global network characteristics predict its function. Results: We introduce a graph-theoretic approach that identifies key regulatory proteins in an organism by analyzing proteins ’ local PPI network structure. We apply the method to the yeast genome and describe several properties of the resulting set of regulatory hubs. Finally, we demonstrate how the identified hubs and putative target gene sets can be used to identify causative, functional regulators of

Various molecular interaction networks have been claimed to follow power-law decay for their global connectivity distribution. It has been proposed that there may be underlying generative models that explain this heavy-tailed behavior by self-reinforcement processes such as classical or hierarchical scale-free network models. Here we analyze a comprehensive data set of protein-protein and transcriptional regulatory interaction networks in yeast, an E. coli metabolic network, and gene activity profiles for different metabolic states in both organisms. We show that in all cases the networks have a heavy-tailed distribution, but most of them present significant differences from a power-law model according to a stringent statistical test. Those few data sets that have a statistically significant fit with a power-law model follow other distributions equally well. Thus, while our analysis supports that both global connectivity interaction networks and activity distributions are heavy-tailed, they are not generally described by any specific distribution model, leaving space for further inferences on generative models. Key words: cellular networks, fat-tailed distributions, maximum likelihood estimation,

© 2008 Wang et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License

The evolutionary mechanisms by which protein interaction networks grow and change are beginning to be appreciated as a major factor shaping their present-day structures and properties. Starting with a consideration of the biases and errors inherent in our current views of these networks, we discuss the dangers of constructing evolutionary arguments from naïve analyses of network topology. We argue that progress in understanding the processes of network evolution is only possible when hypotheses are formulated as plausible evolutionary models and compared against the observed data within the framework of probabilistic modeling. The value of such models is expected to be greatly enhanced as they incorporate more of the details of the biophysical properties of interacting proteins, gene phylogeny, and measurement error and as more advanced methodologies emerge for model comparison and the inference of ancestral network states.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License