Identification of critical molecules via fault diagnosis engineering

Systems biology envisions that the application of complex system engineering approaches to cell signaling molecular networks can lead to novel understandings of complex human disorders. In this paper we show that by developing biologically-driven vulnerability assessment methods, the vulnerability of complex signaling networks to the dysfunction of each molecule can be determined. We have analyzed signaling networks that regulate mitosis and the activity of the transcription factor CREB. Our results indicate that biologically-relevant critical components of intracellular molecular networks can be identified using the proposed systems biology/fault diagnosis engineering technique. The application of this approach can improve our physiological understanding of the functionality of biological systems, can be used as a tool to identify novel genes associated with complex human disorders, and ultimately, has the potential to find the most prominent targets for drug discovery.