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首页> 美国政府科技报告 >New Approach to Construct Pathway Connected Networks and Its Application in Dose Responsive Gene Expression Profiles of Rat Liver Regulated by 2,4DNT
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New Approach to Construct Pathway Connected Networks and Its Application in Dose Responsive Gene Expression Profiles of Rat Liver Regulated by 2,4DNT

机译：构建通路连接网络的新方法及其在2,4DNT调控的大鼠肝脏剂量反应基因表达谱中的应用

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Background: Military and industrial activities have lead to reported release of 2,4-dinitrotoluene (2,4DNT) into soil groundwater or surface water. It has been reported that 2,4DNT can induce toxic effects on humans and other organisms. However the mechanism of 2,4DNT induced toxicity is still unclear. Although a series of methods for gene network construction have been developed, few instances of applying such technology to generate pathway connected networks have been reported. Results: Microarray analyses were conducted using liver tissue of rats collected 24h after exposure to a single oral gavage with one of five concentrations of 2,4DNT. We observed a strong dose response of differentially expressed genes after 2,4DNT treatment. The most affected pathways included: long term depression, breast cancer regulation by stathmin1, WNT Signaling; and PI3K signaling pathways. In addition, we propose a new approach to construct pathway connected networks regulated by 2,4DNT. We also observed clear dose response pathway networks regulated by 2,4DNT. Conclusions: We developed a new method for constructing pathway connected networks. This new method was successfully applied to microarray data from liver tissue of 2,4DNT exposed animals and resulted in the identification of unique dose responsive biomarkers in regards to affected pathways.

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