Adding mechanistic insight in order to understand and better inform researchers as to the target and off target effects of new chemical entities (NCEs) is extremely valuable in development. As such a non-biased approach to determine the cellular transcriptional response could greatly improve efficacy and safety, by potentially determining the molecular initiating event (MIE) of a chemical when exposed to cells.
Transcriptomics, which is the study of mRNA molecules switched on in the cell in order to elicit a cellular response, is one exciting new area of toxicological research currently gaining traction. Through combined expertise from Cyprotex and parent company, Evotec, a new service has been launched which allows the entire transcriptome of the cell to be mapped using an untargeted RNA sequencing approach (RNA-seq). This process has been scaled up and industrialised to give a more in-depth data-rich examination of the molecular phenotype of the cell. As the whole transcriptome of the cell is being profiled, large quantities of data are generated which makes data analysis more challenging. To address this, we have, through our considerable expertise in bioinformatics developed a unique data analysis platform known as PanHunter to manage this process and map the sequencing data to the gene of interest. With machine learning and artificial intelligence (AI) available complicated questions can be easily resolved.
The majority of in vitro toxicology assays detect later stage changes in cellular activity. One advantage of the transcriptomic approach is that adverse effects can be detected at a much earlier stage using highly sensitive mRNA markers, giving improved mechanistic insight. This service allows our clients to work with us using custom cell models, combined with transcriptomics and sophisticated data analysis tools to address their needs.
We are also working on a Drug Induced Liver Injury (DILI) approach whereby a large reference panel of known drugs is being screened with liver specific cellular models, linked to specific toxicological signature profiles to provide a powerful approach to de-risk DILI in future toxicology screening.
To be kept informed about future developments or to enquire about our new custom transcriptomics service, please contact enquiries@cyprotex.com.