Characterization of chemically induced liver injuries using gene co-expression modules.
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Date
2014-09-17
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Abstract
Liver injuries due to ingestion or exposure to chemicals and industrial toxicants pose a serious health risk that may be hard to assess due to a lack of non invasive diagnostic tests Mapping chemical injuries to organ specific damage and clinical outcomes via biomarkers or biomarker panels will provide the foundation for highly specific and robust diagnostic tests Here we have used DrugMatrix a toxicogenomics database containing organ specific gene expression data matched to dose dependent chemical exposures and adverse clinical pathology assessments in Sprague Dawley rats to identify groups of co expressed genes modules specific to injury endpoints in the liver We identified 78 such gene co expression modules associated with 25 diverse injury endpoints categorized from clinical pathology organ weight changes and histopathology Using gene expression data associated with an injury condition we showed that these modules exhibited different patterns of activation characteristic of each injury We further showed that specific module genes mapped to 1 known biochemical pathways associated with liver injuries and 2 clinically used diagnostic tests for liver fibrosis As such the gene modules have characteristics of both generalized and specific toxic response pathways Using these results we proposed three gene signature sets characteristic of liver fibrosis steatosis and general liver injury based on genes from the co expression modules Out of all 92 identified genes 18 20 genes have well documented relationships with liver disease whereas the rest are novel and have not previously been associated with liver disease In conclusion identifying gene co expression modules associated with chemically induced liver injuries aids in generating testable hypotheses and has the potential to identify putative biomarkers of adverse health effects