title: A new approach to construct pathway connected networks and its application in dose responsive gene expression profiles of rat liver regulated by 2,4DNT.
abstract: 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.
authors.affiliation: Indiana University School of Informatics, Indianapolis, IN 46202, USA. sudhir.cr@gmail.com
authors.forename: Sudhir
authors.initials: S
authors.lastname: Chowbina
authors.forename: Youping
authors.initials: Y
authors.lastname: Deng
authors.forename: Junmei
authors.initials: J
authors.lastname: Ai
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Wu
authors.forename: Xin
authors.initials: X
authors.lastname: Guan
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Wilbanks
authors.forename: Barbara Lynn
authors.initials: BL
authors.lastname: Escalon
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Meyer
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Perkins
authors.forename: Jake Y
authors.initials: JY
authors.lastname: Chen
mesh_terms: D000818:Animals; D004136:Dinitrobenzenes / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D050777:Stathmin / Q000235:genetics / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004136:Dinitrobenzenes; D050777:Stathmin; D014874:Water Pollutants, Chemical; D051153:Wnt Proteins; C061082:Stmn1 protein, rat; C016403:2,4-dinitrotoluene; D019869:Phosphatidylinositol 3-Kinases