Multi-Omics in Predictive Toxicology: Development & Application in Environmental Monitoring Programs

By David Faulkner posted 03-16-2016 14:38


If biological sciences in the 20th century were characterized by the birth of molecular biology and the DNA revolution, then the early 21st century will be remembered as the beginning of the “–omics” era. The proliferation of ever more powerful computing, chemical characterization, and sequencing technologies have given rise to genomics, transcriptomics, proteomics, and a galaxy of other -omics disciplines which seek to characterize the full cellular (or organismal) complement of biological molecules for which they are named. These massive screening approaches provide unprecedented insight into mechanisms of toxicity by providing snapshots of the full range of cellular or organismal responses to toxicants.  The presenters at the “Multi-Omics in Predictive Toxicology: Development and Application in Environmental Monitoring Programs” session discussed how -omics technologies may play a role in the development of Adverse Outcome Pathways (AOPs) and the field of environmental monitoring.

-Omics approaches are high-resolution, high-throughput testing methods which suggest an appealing solution to the challenge of addressing the massive array of un-investigated compounds currently in commercial use. Gerald Ankley was part of the group that first articulated the paradigm of AOP, which has been widely embraced by toxicologists and risk assessors, and during this session, he presented on the complexity of analyzing chemical mixtures and fitting -omic data to AOPs. One of the most intriguing ideas that he discussed was FACS-based monitoring—a method of using biological systems to detect what instruments cannot. FACS-based monitoring has the potential to identify previously unmeasured or unknown environmental chemicals by using cells as high-tech canaries in the environmental coal mine to indicate which toxicants are found at biologically relevant detection limits.

Kristine Willett and Bharat Chandramouli discussed the use of epigenomics and metabolomics, respectively, to investigate the effects of various chemicals on the zebrafish, a model organism of growing interest for environmental monitoring. Both presenters agreed with Ankley that -omics technologies offered an effective means of filling in the gaps of AOPs, which may then have predictive use for other chemicals.

Of course, identifying all the salient components of an AOP is a challenging task, particularly when the level of salinity in the water is affecting your fish experiments, as was reported by Daniel Schlenk. Schlenk used a combination of transcriptomics and behavioral assays to demonstrate that the salinity of the water could exacerbate the effects of chlorpyrifos on salmonoid olfactory responses. His talk provided a thoughtful reminder that AOPs are only as useful as they are complete, and that sources of enhanced toxicity may lurk in unexpected places.

Speaking of unexpected places, the session concluded on a high note with a delightful presentation from Caren Helbing, who developed a transcriptomic methodology for investigating non-model species. In the example Helbing presented, she reminded the audience that the African-clawed frog xenopus  (which enjoys wide use as a model organism) diverged evolutionarily from the most common American frogs around 300 million years ago. To get around this issue, untargeted RNA sequencing is used to piece together the genome using Trans-Abyss. Her methodology is particularly exciting for environmental scientists interested in studying sentinel and non-model species in the environment, who heretofore would have to go through the cost and challenge of whole genome sequencing in order to get any genomic data.

Taken together, these presentations offered an exciting look at how -omics technologies may be applied in novel ways to solve some of the big problems of environmental monitoring.