Inferring Gene Regulatory Networks (GRNs) from gene expression data is a major challenge in systems biology. The Path Consistency (PC) algorithm is one of the popular methods in this field. However, as an order dependent algorithm, PC algorithm is not robust because it achieves different network topologies if gene orders are permuted. In addition, the performance of this algorithm depends on the threshold value used for independence tests. Consequently, selecting suitable sequential ordering of nodes and an appropriate threshold value for the inputs of PC algorithm are challenges to infer a good GRN. In this work, we propose a heuristic algorithm, namely SORDER, to find a suitable sequential ordering of nodes. Based on the SORDER algorithm and a suitable interval threshold for Conditional Mutual Information (CMI) tests, a network inference method, namely the Consensus Network (CN), has been developed. In the proposed method, for each edge of the complete graph, a weighted value is defined. This value is considered as the reliability value of dependency between two nodes. The final inferred network, obtained using the CN algorithm, contains edges with a reliability value of dependency of more than a defined threshold. The effectiveness of this method is benchmarked through several networks from the DREAM challenge and the widely used SOS DNA repair network in Escherichia coli. The results indicate that the CN algorithm is suitable for learning GRNs and it considerably improves the precision of network inference. The source of data sets and codes are available at .
Joint modeling of longitudinal data and survival data has been used widely for analyzing AIDS clinical trials, where a biological marker such as CD4 count measurement can be an important predictor of survival. In most of these studies, a normal distribution is used for modeling longitudinal responses, which leads to vulnerable inference in the presence of outliers in longitudinal measurements. Powerful distributions for robust analysis are normal/independent distributions, which include univariate and multivariate versions of the Student's t, the slash and the contaminated normal distributions in addition to the normal. In this paper, a linear-mixed effects model with normal/independent distribution for both random effects and residuals and Cox's model for survival time are used. For estimation, a Bayesian approach using Markov Chain Monte Carlo is adopted. Some simulation studies are performed for illustration of the proposed method. Also, the method is illustrated on a real AIDS data set and the best model is selected using some criteria.
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