Causality inference is the use of computational techniques to predict possible causal relationships for a set of variables, thereby forming a directed network. Causality inference in Gene Regulatory Networks (GRNs) is an important, yet challenging task due to the limits of available data and lack of efficiency in existing causality inference techniques. A number of techniques have been proposed and applied to infer causal relationships in various domains, although they are not specific to regulatory network inference. In this paper, we assess the effectiveness of methods for inferring causal GRNs. We introduce seven different inference methods and apply them to infer directed edges in GRNs. We use time-series expression data from the DREAM challenges to assess the methods in terms of quality of inference and rank them based on performance. The best method is applied to Breast Cancer data to infer a causal network. Experimental results show that Causation Entropy is best, however, highly time-consuming and not feasible to use in a relatively large network. We infer Breast Cancer GRN with the second-best method, TE. The topological analysis of the network reveals that top out-degree genes such as SLC39A5 which are considered central genes, play important role in cancer progression.
With the availability of vast amounts of protein-protein, protein-DNA interactions, and genome-wide mRNA expression data for several organisms, identifying biological complexes has emerged as a major task in systems biology. Most of the existing approaches for complex identification have focused on utilizing one source of data. Recent research has shown that systematic integration of gene profile data with interaction data yields significant patterns. In this paper, we introduce the problem of mining maximal cohesive subnetworks that satisfy user-defined constraints defined over the gene profiles of the reported subnetworks. Moreover, we introduce the problem of finding maximal cohesive patterns which are sets of cohesive genes. Experiments on Yeast and Human datasets show the effectiveness of the proposed approach by assessing the overlap of the discovered subnetworks with known biological complexes. Moreover, GO enrichment analysis shows that the discovered subnetworks are biologically significant.
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