Integrated web-based environment for analysis and control of complex cellular networks

Abstract

An integrated web-based environment for analysis and control of complex biological networks has been established for system level understanding of biological system. The developed biological models are validated by thermodynamic balancing constraints and studied with conservation analysis, pathway analysis, and dynamic simulation in the developed environment. In addition, a systematic approach for metabolic control analysis of any biochemical systems is introduced. The steady-state concentrations, time-varying control coefficients and the responsive changes of sustained oscillatory behaviors are measured following the proposed scheme. A novel methodology exploiting the advantages of the process graph and thermodynamic principles is developed for efficient and effective identification of feasible pathways in this work. The process graph theory and flux balance analysis are applied to produce the physically feasible metabolic networks based on mass balances. This solution is further refined by pathway evaluation based on thermodynamic principles. The selected pathways are believed to be dominant and feasible, providing the crucial information for experimental design. This will save a lot of time and effort for wet experiments. The dynamic simulation tool that has been developed for quantitative and dynamic analysis of cellular network is named as WebCell. It allows the customized modeling as well as the access to model library which stores the published models. The model library can serve as a comprehensive, web-accessible educational system for revisiting publicly available kinetic models. WebCell will be used as a powerful tool for biological researches, the identification of drug targets and industrial applications.