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Systematic Analysis of High-Throughput Transcriptomics to Identify Potential Carcinogens
Citation:
Corton, C. Systematic Analysis of High-Throughput Transcriptomics to Identify Potential Carcinogens. Society of Toxicology 62nd Annual Meeting and ToxExpo 2023, Nashville, TN, March 19 - 23, 2023. https://doi.org/10.23645/epacomptox.23457839
Impact/Purpose:
Presentation to the Society of Toxicology 62nd Annual Meeting and ToxExpo March 2023 part of a joint Japanese SOT-US SOT symposium to be held in Nashville and Tokyo.
Description:
Recent technological advances have moved the field of toxicogenomics from reliance on microarray platforms to high-throughput transcriptomic technologies that measure global gene expression. Gene expression biomarkers are emerging as useful tools for interpreting gene expression profiles to identify perturbations of targets of chemicals including those that exhibit characteristics of carcinogens. Gene expression biomarkers are lists of similarly-regulated genes identified in global gene expression comparisons of cells or tissues 1) exposed to known agonists or antagonists of the transcription factor or 2) after modulation in the expression of the transcription factor itself. We have characterized a set of biomarkers that can be used to screen for chemical carcinogens and that measure many of the characteristics of chemical carcinogens. These include biomarkers for identifying 1) DNA damage (TGx-DDI), 2) endocrine disruption (estrogen and androgen receptors), 3) epigenetic modulation (TGx-HDACi), 4) immune modulation (NF-kB), and 5) modulation of stress factors (Nrf2, MTF-1, HSF1, HIF1a, unfolded protein response). The biomarkers were shown to be very accurate at identifying reference compound activators of each of the pathways (90-98% balanced accuracy). These biomarkers are used to interpret large transcript profile datasets generated on microarrays or by targeted RNA-Seq. The biomarker predictions can be put into the context of the adverse outcome pathway framework to help prioritize chemicals with the greatest risk of their involvement in carcinogenesis. (This abstract does not reflect EPA policy.)
URLs/Downloads:
DOI: Systematic Analysis of High-Throughput Transcriptomics to Identify Potential Carcinogens
CORTON_SOT_03_21_23.PDF (PDF, NA pp, 3006.535 KB, about PDF)