Diagnosing Un-occurred Diseases by Dynamic Network Biomarkers — Detecting the Tipping Points of Biological Processes by Big Data

Abstract

Considerable evidence suggests that during the progression of complex diseases, the deteriorations are not necessarily smooth but are abrupt, and may cause a critical transition from one state to another at a tipping point. Here, we develop a model-free method to detect early-warning signals of such critical transitions (or un-occurred diseases), even with only a small number of samples. Specifically, we theoretically derive an index based on a dynamical network biomarker (DNB) that serves as a general early-warning signal indicating an imminent sudden deterioration before the critical transition occurs. Based on theoretical analyses, we show that predicting a sudden transition from small samples is achievable provided that there are a large number of measurements for each sample, e.g., high-throughput data. We employ gene expression data of three diseases to demonstrate the effectiveness of our method. The relevance of DNBs with the diseases was also validated by related experimental data (e.g., liver cancer, lung injury, influenza, type-2 diabetes) and functional analysis. DNB can also be used for the analysis of nonlinear biological processes, e.g., cell differentiation process.

Biography

Prof. Luonan Chen received BS degree in the Electrical Engineering, from Huazhong University of Science and Technology, and the M.E. and Ph.D. degrees in the electrical engineering, from Tohoku University, Sendai, Japan, in 1984, 1988 and 1991, respectively. From 1997, he was an associate professor of the Osaka Sangyo University, Osaka, Japan, and then a full Professor. Since 2010, he has been a professor and executive director at Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. He was the founding director of Institute of Systems Biology, Shanghai University, and is also research professor at the University of Tokyo since 2010. He was elected as the founding president of Computational Systems Biology Society of OR China, and Chair of Technical Committee of Systems Biology at IEEE SMC Society. He serves as editor or editorial board member for major systems biology related journals. In recent years, he published over 280 SCI journal papers and two monographs (books) in the area of systems biology.