This article is part of the supplement: The ISIBM International Joint Conferences on Bioinformatics, Systems Biology and Intelligent Computing (IJCBS)
A new approach to construct pathway connected networks and its application in dose responsive gene expression profiles of rat liver regulated by 2,4DNT
- Equal contributors
1 Indiana University School of Informatics, Indianapolis, IN 46202, USA
2 Rush University Cancer Center, Rush University Medical Center, Chicago, IL 60612, USA
3 School of Computing, University of Southern Mississippi, Hattiesburg, MS 39406, USA
4 SpecProc Inc., Vicksburg, MS 39180, USA
5 US Army Engineer Research and Development Center, 3909 Halls Ferry Road, Vicksburg, MS 39180, USA
6 Department of Toxicology, University of Louisiana at Monroe, Monroe, LA 70804, USA
7 Department of Computer and Information Science, Purdue School of Science, Indianapolis, IN 46202, USA
8 Indiana Center for Systems Biology and Personalized Medicine, Indianapolis, IN 46202, USA
BMC Genomics 2010, 11(Suppl 3):S4 doi:10.1186/1471-2164-11-S3-S4Published: 1 December 2010
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.
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.
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.