Reconstructing the topology of a signaling network by means of RNA interference (RNAi) technology is an underdetermined problem especially when a single gene in the network is knocked down or observed. In addition, the exponential search space limits the existing methods to small signaling networks of size 10-15 genes. In this paper, we propose integrating RNAi data with a reference physical interaction network. We formulate the problem of signaling network reconstruction as finding the minimum number of edit operations on a given reference network. The edit operations transform the reference network to a network that satisfies the RNAi observations. We show that using a reference network does not simplify the computational complexity of the problem. Therefore, we propose two methods which provide near optimal results and can scale well for reconstructing networks up to hundreds of components. We validate the proposed methods on synthetic and real data sets. Comparison with the state of the art on real signaling networks shows that the proposed methodology can scale better and generates biologically significant results.

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Subgraphs that occur in complex networks with significantly higher frequency than those in randomised networks are called network motifs. Such subgraphs often play important roles in the functioning of those networks. Finding network motifs is a computationally challenging problem. The main difficulties arise from the fact that real networks are large and the size of the search space grows exponentially with increasing network and motif size. Numerous methods have been developed to overcome these challenges. This paper provides a comparative study of the key network motif discovery algorithms in the literature and presents their algorithmic details on an example network.