title: Repeated small perturbation approach reveals transcriptomic steady states.
abstract: The study of biological systems dynamics requires elucidation of the transitions of steady states. A "small perturbation" approach can provide important information on the "steady state" of a biological system. In our experiments, small perturbations were generated by applying a series of repeating small doses of ultraviolet radiation to a human keratinocyte cell line, HaCaT. The biological response was assessed by monitoring the gene expression profiles using cDNA microarrays. Repeated small doses (10 J/m2) of ultraviolet B (UVB) exposure modulated the expression profiles of two groups of genes in opposite directions. The genes that were up-regulated have functions mainly associated with anti-proliferation/anti-mitogenesis/apoptosis, and the genes that were down-regulated were mainly related to proliferation/mitogenesis/anti-apoptosis. For both groups of genes, repetition of the small doses of UVB caused an immediate response followed by relaxation between successive small perturbations. This cyclic pattern was suppressed when large doses (233 or 582.5 J/m2) of UVB were applied. Our method and results contribute to a foundation for computational systems biology, which implicitly uses the concept of steady state.
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Huang
authors.forename: Wun-Yi
authors.initials: WY
authors.lastname: Shu
authors.forename: Min-Lung
authors.initials: ML
authors.lastname: Tsai
authors.forename: Chi-Shiun
authors.initials: CS
authors.lastname: Chiang
authors.forename: Cheng-Wei
authors.initials: CW
authors.lastname: Chang
authors.forename: Chiu-Ting
authors.initials: CT
authors.lastname: Chang
authors.forename: Ian C
authors.initials: IC
authors.lastname: Hsu
mesh_terms: D000465:Algorithms; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000528:radiation effects; D053263:Gene Regulatory Networks / Q000235:genetics / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000528:radiation effects*; D007700:Kinetics; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000235:genetics / Q000528:radiation effects; D059467:Transcriptome / Q000235:genetics* / Q000528:radiation effects*; D014466:Ultraviolet Rays