A biochemical network modeling of a whole-cell

Abstract

All cellular processes can be ultimately understood in terms of respective fundamental biochemical interactions between molecules, which can be modeled as networks. Very often, these molecules are shared by more than one process, therefore interconnecting them. Despite this effect, cellular processes are usually described by separate networks with heterogeneous levels of detail, such as metabolic, protein–protein interaction, and transcription regulation networks. Aiming at obtaining a unified representation of cellular processes, we describe in this work an integrative framework that draws concepts from rule-based modeling. In order to probe the capabilities of the framework, we used an organism-specific database and genomic information to model the whole-cell biochemical network of the Mycoplasma genitalium organism. This modeling accounted for 15 cellular processes and resulted in a single component network, indicating that all processes are somehow interconnected. The topological analysis of the network showed structural consistency with biological networks in the literature. In order to validate the network, we estimated gene essentiality by simulating gene deletions and compared the results with experimental data available in the literature. We could classify 212 genes as essential, being 95% of them consistent with experimental results. Although we adopted a relatively simple organism as a case study, we suggest that the presented framework has the potential for paving the way to more integrated studies of whole organisms leading to a systemic analysis of cells on a broader scale. The modeling of other organisms using this framework could provide useful large-scale models for different fields of research such as bioengineering, network biology, and synthetic biology, and also provide novel tools for medical and industrial applications.