Computational protocol: Toxicogenomic analysis of exposure to TCDD, PCB126 and PCB153: identification of genomic biomarkers of exposure to AhR ligands

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Protocol publication

[…] Gene regulatory regions spanning 5000 bp above and 1000 bp below the transcriptional start site of target genes were obtained from the University of California, Santa Cruz, Genome Browser using Entrez Gene GeneID numbers. All obtained sequences were analyzed for core DRE sequences (5'-GCGTG-3') using MatInspector (Genomatix Software GmbH, Munchen, Germany). Putative DREs were those with a core similarity of 1.0 and matrix similarity equal to or greater than the optimized matrix threshold []. [...] Changes in gene expression associated with TCDD, PCB126 and PCB153 exposure were compared with changes in gene expression associated with rat hepatocellular adenoma (HCA) [], human HCA []and human intrahepatic cholangiocarcinoma (ICC) [,]. Eighty-one percent of the human HCA tumors were from males [] while 52% [] and 41% [] of the human ICC tumors were from males. Our approach was limited in that the HCA and ICC expression data was not reported on a gender specific basis thus preventing us from identifying shared gene responses based on gender. Ortholog identification and gene annotation of gene array data obtained from published studies was accomplished using ArrayTrack (Food and Drug Administration, NTCR) and/or NetAffix™ (Affymetrix Inc.) []. […]

Pipeline specifications

Software tools GeneID, MatInspector, ArrayTrack
Databases Gene
Applications Gene expression microarray analysis, Genome data visualization
Organisms Rattus norvegicus
Diseases Neoplasms, Adenoma, Liver Cell, Cholangiocarcinoma