Local graph alignment and motif search in biological networks

Sequence comparison and alignment has had an enormous impact on our understanding of evolution, biology, and disease. Comparison and alignment of biological networks will likely have a similar impact. Existing network alignments use information external to the networks, such as sequence, because no good algorithm for purely topological alignment has yet been devised. In this paper, we present a novel algorithm based solely on network topology, that can be used to align any tw...

A new heuristic based on vertex invariants is developed to rapidly distinguish non-isomorphic graphs to a desired level of accuracy. The method is applied to sample subgraphs from an E.coli protein interaction network, and as a probe for discovery of extended motifs. The network's structure is described using statistical properties of its $N$-node subgraphs for $N\leq 14$. The Zipf plots for subgraph occurrences are robust power laws that do not change when rewiring the netwo...

We generalize a sampling algorithm for lattice animals (connected clusters on a regular lattice) to a Monte Carlo algorithm for `graph animals', i.e. connected subgraphs in arbitrary networks. As with the algorithm in [N. Kashtan et al., Bioinformatics 20, 1746 (2004)], it provides a weighted sample, but the computation of the weights is much faster (linear in the size of subgraphs, instead of super-exponential). This allows subgraphs with up to ten or more nodes to be sample...

Topological features of gene regulatory networks can be successfully reproduced by a model population evolving under selection for short dynamical attractors. The evolved population of networks exhibit motif statistics, summarized by significance profiles, which closely match those of {\it E. coli, S. cerevsiae} and {\it B. subtilis}, in such features as the excess of linear motifs and feed-forward loops, and deficiency of feedback loops. The slow relaxation to stasis is a ha...

Many real world networks contain a statistically surprising number of certain subgraphs, called network motifs. In the prevalent approach to motif analysis, network motifs are detected by comparing subgraph frequencies in the original network with a statistical null model. In this paper we propose an alternative approach to motif analysis where network motifs are defined to be connectivity patterns that occur in a subgraph cover that represents the network using minimal total...

Because of the huge number of graphs possible even with a small number of nodes, inference on network structure is known to be a challenging problem. Generating large random directed graphs with prescribed probabilities of occurrences of some meaningful patterns (motifs) is also difficult. We show how to generate such random graphs according to a formal probabilistic representation, using fast Markov chain Monte Carlo methods to sample them. As an illustration, we generate re...

Developing and maintaining life requires a lot of computation. This is done by gene regulatory networks. But we have little understanding of how this computation is organized. I show that there is a direct correspondence between the structural and functional building blocks of regulatory networks, which I call regulatory motifs. I derive a simple bound on the range of function that these motifs can perform, in terms of the local network structure. I prove that this range is a...

In this paper, we present a survey of the use of graph theoretical techniques in Biology. In particular, we discuss recent work on identifying and modelling the structure of bio-molecular networks, as well as the application of centrality measures to interaction networks and research on the hierarchical structure of such networks and network motifs. Work on the link between structural network properties and dynamics is also described, with emphasis on synchronization and dise...

Complex interactions between genes or proteins contribute a substantial part to phenotypic evolution. Here we develop an evolutionarily grounded method for the cross-species analysis of interaction networks by {\em alignment}, which maps bona fide functional relationships between genes in different organisms. Network alignment is based on a scoring function measuring mutual similarities between networks taking into account their interaction patterns as well as sequence simila...

With the advent of high-throughput wet lab technologies the amount of protein interaction data available publicly has increased substantially, in turn spurring a plethora of computational methods for in silico knowledge discovery from this data. In this paper, we focus on parameterized methods for modeling and solving complex computational problems encountered in such knowledge discovery from protein data. Specifically, we concentrate on three relevant problems today in prote...