title: Differential dynamic properties of scleroderma fibroblasts in response to perturbation of environmental stimuli.
abstract: Diseases are believed to arise from dysregulation of biological systems (pathways) perturbed by environmental triggers. Biological systems as a whole are not just the sum of their components, rather ever-changing, complex and dynamic systems over time in response to internal and external perturbation. In the past, biologists have mainly focused on studying either functions of isolated genes or steady-states of small biological pathways. However, it is systems dynamics that play an essential role in giving rise to cellular function/dysfunction which cause diseases, such as growth, differentiation, division and apoptosis. Biological phenomena of the entire organism are not only determined by steady-state characteristics of the biological systems, but also by intrinsic dynamic properties of biological systems, including stability, transient-response, and controllability, which determine how the systems maintain their functions and performance under a broad range of random internal and external perturbations. As a proof of principle, we examine signal transduction pathways and genetic regulatory pathways as biological systems. We employ widely used state-space equations in systems science to model biological systems, and use expectation-maximization (EM) algorithms and Kalman filter to estimate the parameters in the models. We apply the developed state-space models to human fibroblasts obtained from the autoimmune fibrosing disease, scleroderma, and then perform dynamic analysis of partial TGF-beta pathway in both normal and scleroderma fibroblasts stimulated by silica. We find that TGF-beta pathway under perturbation of silica shows significant differences in dynamic properties between normal and scleroderma fibroblasts. Our findings may open a new avenue in exploring the functions of cells and mechanism operative in disease development.
authors.affiliation: Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston (UTHSC-H), Houston, Texas, USA.
authors.forename: Momiao
authors.initials: M
authors.lastname: Xiong
authors.forename: Frank C
authors.initials: FC
authors.lastname: Arnett
authors.forename: Xinjian
authors.initials: X
authors.lastname: Guo
authors.forename: Hao
authors.initials: H
authors.lastname: Xiong
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000465:Algorithms; D002478:Cells, Cultured; D004777:Environment; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology*; D053263:Gene Regulatory Networks; D006801:Humans; D010812:Physical Stimulation; D012595:Scleroderma, Systemic / Q000473:pathology*; D015398:Signal Transduction; D012822:Silicon Dioxide / Q000494:pharmacology; D049490:Systems Biology / Q000379:methods*; D016212:Transforming Growth Factor beta
chemical_list: D016212:Transforming Growth Factor beta; D012822:Silicon Dioxide