Abstract
BackgroundGene networks are considered to represent various aspects of molecular biological systems meaningfully because they naturally provide a systems perspective of molecular interactions. In this respect, the functional understanding of the transcriptional regulatory network is considered as key to elucidate the functional organization of an organism.ResultsIn this paper we study the functional robustness of the transcriptional regulatory network of S. cerevisiae. We model the information processing in the network as a first order Markov chain and study the influence of single gene perturbations on the global, asymptotic communication among genes. Modification in the communication is measured by an information theoretic measure allowing to predict genes that are 'fragile' with respect to single gene knockouts. Our results demonstrate that the predicted set of fragile genes contains a statistically significant enrichment of so called essential genes that are experimentally found to be necessary to ensure vital yeast. Further, a structural analysis of the transcriptional regulatory network reveals that there are significant differences between fragile genes, hub genes and genes with a high betweenness centrality value.ConclusionOur study does not only demonstrate that a combination of graph theoretical, information theoretical and statistical methods leads to meaningful biological results but also that such methods allow to study information processing in gene networks instead of just their structural properties.
Highlights
Gene networks are considered to represent various aspects of molecular biological systems meaningfully because they naturally provide a systems perspective of molecular interactions
The major objective of this paper is to investigate the functional robustness of the transcriptional regulatory network (TRN) of S. cerevisiae with respect to single gene perturbations
Single gene perturbations In this paper we study the effect of single gene perturbations on the information processing in the transcriptional regulatory network of yeast
Summary
Gene networks are considered to represent various aspects of molecular biological systems meaningfully because they naturally provide a systems perspective of molecular interactions. Due to the fundamental insight that biological processes should be studied holistically [2,3,4] instead of reductionistically, systems based approaches are of central importance in this respect [5] For this reason, it is no surprise that network related studies experience an enormous interest starting with the investigation of small-world [6,7] and scale-free [8,9] networks in the mid 1990's followed by numerous studies devoted to the analysis of complex network topologies and their properties in general [8,10,11,12,13,14]. Functional robustness is considered a key player for our understanding regarding the interplay of network structure and network dynamics leading to the emergence of life as omnipresent around us [9,2123]
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