Unraveling gene-gene interactions regulated by ligands of the aryl hydrocarbon receptor.
The co-expression of genes coupled to additive probabilistic relationships was used to identify gene sets predictive of the complex biological interactions regulated by ligands of the aryl hydrocarbon receptor ((Italic)Ahr(/Italic)). To maximize the number of possible gene-gene combinations, data sets from murine embryonic kidney, fetal heart, and vascular smooth muscle cells challenged (Italic)in vitro(/Italic) with ligands of the (Italic)Ahr(/Italic) were used to create predictor/training data sets. Biologically relevant gene predictor sets were calculated for (Italic)Ahr(/Italic), cytochrome P450 1B1, insulin-like growth factor-binding protein-5, lysyl oxidase, and osteopontin. Transcript levels were categorized into ternary expressions and target genes selected from the data set and tested for all possible combinations using three gene sets as predictors of transitional level. The goodness of prediction for each set was quantified using a multivariate nonlinear coefficient of determination. Evidence is presented that predictor gene combinations can be effectively used to resolve gene-gene interactions regulated by (Italic)Ahr(/Italic) ligands. (Italic)Key words:(/Italic) aryl hydrocarbon receptor, bioinformatics, gene networks, genomics. (Italic)Environ Health Perspect (/Italic)112:403-412 (2004). [Online 14 January 2004]
Johnson
Charles D
CD
Department of Biochemistry and Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville Health Sciences Center, Louisville, KY 40292, USA.
Balagurunathan
Yoganand
Y
Tadesse
Mahlet G
MG
Falahatpisheh
M Hadi
MH
Brun
Marcel
M
Walker
Mary K
MK
Dougherty
Edward R
ER
Ramos
Kenneth S
KS
D000818:Animals; D004785:Environmental Pollutants / Q000633:toxicity; D005786:Gene Expression Regulation; D023281:Genomics; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics* / Q000502:physiology*; D014158:Transcription, Genetic
D004785:Environmental Pollutants; D008024:Ligands; D018336:Receptors, Aryl Hydrocarbon