Identifying gene-protein interactions in response to environmental estrogenic chemicals using Bayesian networks: its implication in the etiology of pulmonary vascular lesions
Chan, F., Marinova, D. and Anderssen, R.S. (eds) MODSIM2011, 19th International Congress on Modelling and Simulation. · 2011
Despite the extensive research in the field of vascular proliferative disease, the complex interaction of genes with environmental factors with respect to its impact on this disease is not yet fully understood.To date, results from the literature show no direct studies of vascular gene-environment interactions.Vascular lesions consist of actively proliferating endothelial cells that can lead to a tissue mass that blocks the artery and increases arterial pressure.Severe vascular lesions consequentially lead to right ventricular heart failure and death.This outcome is approximately twice more common in women than in men, but whether it may be attributed to the hormone estrogen is not clear.Based on the limited evidence, it appears that estrogenic environmental chemicals play a role in vascular lesion formation.In this study, Bayesian Networks was used to study which genes are influenced by proteins that we previously identified to be modulated by exposure to the environmental estrogen PCB153 and natural estrogen 17β-estradiol.From the 96 spots obtained in our 2D-DIGE, we selected 13 spots for further protein identification analysis.The analyses identified 11 of the 13 spots of interest with high confidence protein score CI that was greater than 99%.The differentially expressed proteins regulated by PCB153 and estradiol were analyzed using IPA software to identify significant networks.The biological significance of TGFB1 network identified by IPA analysis coupled with the fact that some of the 11 identified proteins are involved in gene transcription lead us to use Bayesian networks to determine whether our identified proteins had any relation to our gene array data from similar estrogenic exposures.While our findings do not reveal any mechanisms involved in estrogen-induced vascular lesion formation, the identified relationships do provide a potential target pathway for future mechanistic studies.