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TimeDelay-ARACNE: Reverse engineering of gene networks from time-course data by an information theoretic approach

DOI: 10.1186/1471-2105-11-154

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In this paper we show how the ARACNE (Algorithm for the Reconstruction of Accurate Cellular Networks) algorithm can be used for gene regulatory network inference in the case of time-course expression profiles. The resulting method is called TimeDelay-ARACNE. It just tries to extract dependencies between two genes at different time delays, providing a measure of these dependencies in terms of mutual information. The basic idea of the proposed algorithm is to detect time-delayed dependencies between the expression profiles by assuming as underlying probabilistic model a stationary Markov Random Field. Less informative dependencies are filtered out using an auto calculated threshold, retaining most reliable connections. TimeDelay-ARACNE can infer small local networks of time regulated gene-gene interactions detecting their versus and also discovering cyclic interactions also when only a medium-small number of measurements are available. We test the algorithm both on synthetic networks and on microarray expression profiles. Microarray measurements concern S. cerevisiae cell cycle, E. coli SOS pathways and a recently developed network for in vivo assessment of reverse engineering algorithms. Our results are compared with ARACNE itself and with the ones of two previously published algorithms: Dynamic Bayesian Networks and systems of ODEs, showing that TimeDelay-ARACNE has good accuracy, recall and F-score for the network reconstruction task.Here we report the adaptation of the ARACNE algorithm to infer gene regulatory networks from time-course data, so that, the resulting network is represented as a directed graph. The proposed algorithm is expected to be useful in reconstruction of small biological directed networks from time course data.In order to understand cellular complexity much attention is placed on large dynamic networks of co-regulated genes at the base of phenotype differences. One of the aims in molecular biology is to make sense of high-throughput data like


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