Harmonization of Transcriptomic and Methylomic Analysis in Environmental Epidemiology Studies for Potential Application in Chemical Risk Assessment
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Changes in the regulation of gene transcription and DNA methylation related to the toxic effects of a chemical precede observable clinical changes in a biological system. Technological advances have made it possible to measure these changes and analyze this type of data, which has fostered the acceptance for the collection and analysis of high-throughput “omics” data in human health risk assessment. The development and application of a novel analytical workflow that utilized gene set enrichment analysis (GSEA) in combination with pathway-level benchmark dose (BMD) modeling was employed to harmonize the analysis of data from an epidemiological study and yielded evidence to support the association between transcriptomic and methylomic regulation in response to environmental exposure to arsenic. This approach not only identified pathways for both platforms known to be associated with arsenic exposure but also provided biological plausibility and insight for the toxic effects of arsenic by comparing the direction and nature of dysregulation between the two omics sources; similar ranges for pathway-level BMDs suggest arsenic-induced toxicity is mediated by coordinated changes in transcription and methylation.
The views expressed in the abstract are those of the authors and do not necessarily reflect the views or policies of the U.S. EPA.