Delving Deeper into Drug-induced Cardiotoxicity using High Content Imaging, Calcium Flux and Transcriptomics

In March, Cyprotex headed to San Diego for the 61st Annual Society of Toxicology Meeting (SOT) and ToxExpo, March 27-31, 2022. At the event we presented our latest research in the fields of hepato-, neuro-, cardio- and immunotoxicology.

Today we take a look at the work performed for the poster: Evaluating functional and structural cardiotoxicants using calcium flux, high-content imaging and high throughput transcriptomics

In a previous blog, we discussed our work in detecting early cardiac cellular morphology changes and cytotoxicity alongside functional profiling in early in vitro screening studies. Expanding upon this research, we profiled 42 compounds across several therapeutic indications using both functional and structural endpoints, as well as transcriptomic analysis using whole genome high-throughput RNA-sequencing (RNA-seq).

RNA-seq uses next-generation sequencing to reveal the presence and quantity of RNA in a sample in a high throughput manner (ScreenSeqTM). By continuously monitoring the changes within the cellular transcriptome, it is possible to detect the adverse outcome pathways related to drug-induced toxicity (in this case, cardiotoxicity) in a particular cell type. For this research, we used human-induced pluripotent stem cell-derived cardiomyocytes.

The pathways highlighted by RNA-seq can be grouped using biological context and relevant enrichment profiles, allowing for further investigation of the fold-change of differentially expressed genes associated with pathways of interest. The work described within this latest poster highlights the power of a combined set of data readouts to give detailed and accurate cardiotoxicity predictions. In addition, the introduction of transcriptomics into the toxicologist’s toolbox promises greater insight into potential drug-induced toxicity risk.

Find out more about our presence at SOT here.

To download the poster, click here.

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