ICCVAM Biennial Report 2018-2019

NIEHS scientists are using two approaches to develop computational models for predicting the potential of substances to cause toxicity to the heart and vascular system.

In one approach, a weighted gene coregulation network analysis was applied to rat heart gene expression data from the DrugMatrix database to map gene expression relationships associated with cardiotoxic stress. The map revealed sets of genes linked to biological processes with potential relevance to cardiotoxicity. Applied to known cardiotoxic substances such as anthracyclines, corticosteroids, and kinase inhibitors, the map may provide an approach for exploring mechanisms of cardiotoxicity. An abstract describing this project (Rahman et al.) was accepted for presentation at the SOT 2020 annual meeting.

The second approach used in silico tools and in vitro HTS data to generate bioactivity scores for environmental chemicals against molecular and cellular targets known to mediate bioactivity in the cardiovascular system. These scores support a visualization tool and ranking system that can be used to screen and prioritize chemicals with limited or no toxicity information for further assessment. An abstract describing this project (Krishna et al.) was accepted for presentation at the SOT 2020 annual meeting.