Systematic component selection for gene-network refinement

Abstract

We have developed a method that uses gene expression data as well as interaction data between cell components to define a set of genes that we use for our modeling. In a subsequent step, we estimate the parameters of our model of piecewise linear differential equations and evaluate the results simulating the behavior of the system with our model. We have applied our method to the DNA repair system of Mycobacterium tuberculosis. Our analysis predicts that the gene Rv2719c plays an important role in this system.

Identifying Genes of Gene Regulatory Networks Using Formal Concept Analysis

“…Let K = (S ∪ S * , E) be an undirected complete bipartite graph, with vertex set S ∪ S * and undirected edges E existing between each pair of vertices (v 1 , v 2 ) with v 1 ∈ S, v 2 ∈ S * . Given a significance level α > 0 we compute Q min as the maximum of the (α/2)% smallest correlation coefficients between the seed genes and genes in G. Similarly, Q max is obtained as the minimum of the (α/2)% largest of these values (see also [Radde et al, 2006]). We define an edge to be significant with respect to a given α if the correlation coefficient between the two expression profiles of the corresponding genes is smaller than Q min or greater than Q max .…”

“…In this paper we will present a method which finds genes that might have an important influence on the gene regulatory network defined by the seed genes and that should be added to this network. A mathematical method, called formal concept analysis, is used to detect a list of candidate genes that can be analyzed afterwards in the same way as proposed in [Radde et al, 2006]. In that paper a graph theoretical approach was used to detect such a list of genes, which is further described in [Cabusora et al, 2005].…”

“…Our method is based on formal concept analysis and is applied to the DNA repair system of Mycobacterium tuberculosis. The method proposed in [Radde et al, 2006] uses the same data set so that the methods can be compared with each other. The bacterium M. tuberculosis has been discovered by Robert Koch in 1882.…”

“…Additionally to the SOS regulation there exists another mechanism in M. tuberculosis to activate some of the SOS genes in the case of DNA damage (see [Dullaghan et al, 2002]). In [Radde et al, 2006] the gene Rv2719c is predicted to play an important role in the DNA repair system. We will compare our results with this prediction.…”

“…In section 'Methods' we will present the analysis of gene expression data and interaction data with formal concept analysis followed by the statistical analysis proposed by [Radde et al, 2006]. In section 'Application' we apply this method to data of M. tuberculosis and in section 'Discussion' we will compare the results with the results given in [Radde et al, 2006] and discuss the prospectives of our approach. The section 'Conclusion' will give a short summary of this paper.…”