title: Deciphering deterioration mechanisms of complex diseases based on the construction of dynamic networks and systems analysis.
abstract: The early diagnosis and investigation of the pathogenic mechanisms of complex diseases are the most challenging problems in the fields of biology and medicine. Network-based systems biology is an important technique for the study of complex diseases. The present study constructed dynamic protein-protein interaction (PPI) networks to identify dynamical network biomarkers (DNBs) and analyze the underlying mechanisms of complex diseases from a systems level. We developed a model-based framework for the construction of a series of time-sequenced networks by integrating high-throughput gene expression data into PPI data. By combining the dynamic networks and molecular modules, we identified significant DNBs for four complex diseases, including influenza caused by either H3N2 or H1N1, acute lung injury and type 2 diabetes mellitus, which can serve as warning signals for disease deterioration. Function and pathway analyses revealed that the identified DNBs were significantly enriched during key events in early disease development. Correlation and information flow analyses revealed that DNBs effectively discriminated between different disease processes and that dysfunctional regulation and disproportional information flow may contribute to the increased disease severity. This study provides a general paradigm for revealing the deterioration mechanisms of complex diseases and offers new insights into their early diagnoses.
authors: 1] School of Mathematics and Statistics, Wuhan University, Wuhan 430072, China [2] School of Science, Wuhan Institute of Technology, Wuhan 430074, China.
authors: Yuanyuan
authors: Y
authors: Li
authors: School of Mathematics and Statistics, Wuhan University, Wuhan 430072, China.
authors: Suoqin
authors: S
authors: Jin
authors: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors: Lei
authors: L
authors: Lei
authors: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors: Zishu
authors: Z
authors: Pan
authors: School of Mathematics and Statistics, Wuhan University, Wuhan 430072, China.
authors: Xiufen
authors: X
authors: Zou
mesh_terms: D015415:Biomarkers; D016022:Case-Control Studies; D042241:Early Diagnosis; D053263:Gene Regulatory Networks; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D008954:Models, Biological; D015203:Reproducibility of Results; D049490:Systems Biology / Q000379:methods
chemical_list: D015415:Biomarkers