The second November installment of our webinar series is with Carole Yauk, PhD, University of Ottawa took place on November 29th at 11 ET.
Dr. Yauk will explored the utility of error-corrected next-generation sequencing to quantify and characterize mutations.
What you’ll learn:
- Introduction to error-corrected next-generation sequencing (ecNGS) and its advantages over conventional approaches in chemical mutagenicity assessment;
- Proof of concept studies demonstrating high inter-laboratory concordance and agreement between mutant frequencies measured by ecNGS and conventional mutation analysis assays;
- Evaluation of the added value of mechanistic information produced via ecNGS;
- A roadmap to facilitate regulatory validation and uptake.
All registered participants will receive access to the webinar recording. We look forward to hosting you!
Watch the Recording!
Dr. Carole Yauk:
Carole Yauk was the lead scientist of the Genomics Laboratory in the Environmental Health Science and Research Bureau at Health Canada for 18 years. She joined the University of Ottawa’s Department of Biology as a professor in September 2020, where she holds the Canada Research Chair in Genomics and the Environment. Her research broadly focuses on the development and implementation of genomic tools for human health risk assessment of environmental chemicals. She is involved in various international committees to advance the use of genomics, including within the Health and Environmental Sciences Institute (HESI) Emerging Systems Toxicology in the Assessment of Risk (eSTAR) and Genetic Toxicology Technical (GTTC) Committees. She has served as a Canadian delegate to the Organisation for Economic Co-operation and Development (OECD) Extended Advisory Group for Molecular Screening and Toxicogenomics since 2012. Within the OECD, she is involved in the development of ‘omics reporting frameworks for regulatory submissions. She is Past-President of the Environmental Mutagenesis and Genomics Society and an editorial board member of several journals focused on mutagenesis and genetic toxicology.
Mutagenicity testing is a critical component of human and environmental health risk assessment because mutations can lead to cancer and heritable genetic diseases. Regulatory agencies worldwide have established test guidelines to determine whether chemicals cause mutations. These conventional tests suffer from critical limitations including: (1) reliance on bacterial mutagenicity as a gold standard; (2) measurement of a single reporter gene at a time and/or the requirement of genetically modified organism that requires standalone experiments; and (3) the requirement for extensive additional work to generate mechanistic data to identify nucleotide targets. Error-corrected next-generation sequencing (ecNGS) enables highly precise quantification of mutation frequency and characterization of spectrum in potentially any species, tissue, and cell culture model. My research group is collaborating extensively with Health Canada, TwinStrand BioSciences, and partners within the Health and Environmental Sciences Institute (HESI) to promote the adoption of ecNGS to modernize regulatory mutagenicity assessment. I will present foundational studies from our collaborative studies using in vivo and in vitro models that are contributing to these efforts. The proof of concept and validation work we are undertaking includes: (a) studying mutagenic responses by ecNGS to determine performance across different genotoxic modes of action and model systems; (b) establishing degree of qualitative and quantitative concordance relative to conventional mutagenicity endpoints; (c) investigating optimal study designs; and (d) exploring the added-value of the mechanistic information produced by ecNGS. We show that ecNGS can readily be used to detect prototypical mutagenic responses in numerous models and shows high concordance with the lacZ transgenic mutation assay. In addition to mutation frequency, the approach readily informs mutation spectrum to reveals the nucleotide targets impacted by chemical mutagens, which informs mechanism of action. Moreover, our experiments have shown excellent cross-laboratory agreement, which places the technology in a strong position for additional cross-laboratory validation trials. This work contributes to the larger efforts being undertaken within the HESI ecNGS working group, who are developing a roadmap to accelerate the adoption of ecNGS for both the near-term (e.g., complement existing assay) and long-term (e.g., replace conventional mutagenicity tests).
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