Correlation of gene expression with physiological functions: Examples of pulmonary blood vessel rheology, hypoxic hypertension, and tissue remodeling.
Microarray gene chip technology is a powerful invention looking for applications. A general principle is proposed here to direct the power of the technology toward physiology, medicine, and pharmacology. Our principle is to match quantitative measures of gene expression with the trend of mathematical parameters that describe biological functions. Mathematical parameterization is the heart. The procedure is illustrated by lung physiology, including the hypoxic hypertension, rheological properties of the tissues, and the remodeling of the pulmonary arterial wall under hypertensive stress. We show first how to reduce the experimental results on these physiological functions into mathematical formulas, and how the parameters of these formulas describe the functional trends precisely. Then under the assumption that the microarray reveals gene activities quantitatively, we match the trends of the gene activity with the trends of the functional parameters. Genes whose trends do match are interpreted as relevant to the functions. Those that do not match are considered irrelevant to the functions. The more functions we consider, the fewer will be the number of genes that are relevant to all functions. Thus we learn about the generality and specificity of the influence of genes on physiology.
Huang
W
W
Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
Sher
Y P
YP
Peck
K
K
Fung
Y C
YC
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006976:Hypertension, Pulmonary / Q000235:genetics / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology; D008168:Lung / Q000098:blood supply*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010100:Oxygen / Q000494:pharmacology; D011651:Pulmonary Artery / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012212:Rheology; D013314:Stress, Mechanical
D010100:Oxygen