Exploiting advances in transcriptomics to improve on human-relevant toxicology

Abstract Modern toxicology is challenged in its aspiration to test and risk-assess the myriad of chemicals humans potentially can be exposed to. We still lack sufficient data to perform proper human risk assessments for a large proportion of environmental chemicals, and we still know very little about many of the molecular mechanisms that cause adverse effects. In turn, lack of mechanistic insight stalls the development of more cost-efficient and high-throughput alternative assays, which is a prerequisite if we are to deal with the large number of untested compounds. One way to help speed up the effort is to take advantage of the many advances in genomics technologies and apply them to toxicity testing strategies or at the very least use them to better characterize the causative molecular mechanisms. For instance, single-cell digital gene expression (DGE)–sequencing and single-cell RNA (scRNA)–sequencing techniques hold great promise for not only enabling the analyses of large sample sizes at low cost but also capturing toxicomolecular events and genomic susceptibilities at the cellular level. In this article, we discuss some of the advances in transcriptomics and how they can be applied to toxicology to advance human-relevant risk assessment.