Network Modeling and Control of Dynamic Disease Pathways, Review and Perspectives.

Dynamic disease pathways are a combination of complex dynamical processes among bio-molecules in a cell that leads to diseases. Network modeling of disease pathways considers disease-related bio-molecules (e.g. DNA, RNA, transcription factors, enzymes, proteins, and metabolites) and their interaction (e.g. DNA methylation, histone modification, alternative splicing, and protein modification) to study disease progression and predict therapeutic responses. These bio-molecules and their interactions are the basic elements in the study of the misregulation in the disease-related gene expression that lead to abnormal cellular responses. Gene regulatory networks, cell signaling networks, and metabolic networks are the three major types of intracellular networks for the study of the cellular responses elicited from extracellular signals. The disease-related cellular responses can be prevented or regulated by designing control strategies to manipulate these extracellular or other intracellular signals. The paper reviews the regulatory mechanisms, the dynamic models, and the control strategies for each intracellular network. The applications, limitations and the prospective for modeling and control are also discussed.