In this webinar, you will learn from experts at Health Canada about:
- How Duplex Sequencing enables precise quantification of mutation frequency with a broader range of characterization and greater sensitivity
- Performance across different genotoxic modes of action and tissue types
- Concordance with conventional mutagenicity testing endpoints
- Ability to produce data regarding mutational mechanisms
Webinar Details
The coming revolution in mutagenicity testing: application of Duplex Sequencing to quantify and characterize mutations
January 17, 12 pm EST
Abstract: Evaluation of a substance’s potential to cause mutagenicity is a critical component of human and environmental health risk assessment. Regulatory agencies worldwide have developed test guidelines to determine whether chemicals cause mutations. While commonly used tests under these guidelines have served the regulatory community well, they measure mutations in one reporter gene and/or require transgenic rodent models and standalone experiments. Duplex Sequencing (DS) is an error-corrected next-generation sequencing (ecNGS) technology that enables highly precise quantification of mutation frequency and characterization of spectrum in potentially any species, tissue, and cell culture model. The Marchetti lab at Health Canada has conducted foundational studies using TwinStrand DuplexSeqTM Mouse and Human Mutagenesis Assays and established laboratory and bioinformatic procedures to: (a) explore mutagenic responses by DS to confirm performance across different genotoxic modes of action and diverse tissues/models; (b) evaluate qualitative and quantitative concordance relative to conventional mutagenicity endpoints; (c) define optimal experimental designs; and (d) investigate the added-value of the mechanistic information produced by DS. The work thus far indicates a robust ability to detect mutations by DS for prototypical mutagenic exposures in numerous models and concordance of DS mutation frequencies with conventional endpoints.
Furthermore, both DuplexSeqTM Mouse and Human Mutagenesis Panels show remarkable cross-laboratory reproducibility. Altogether, these efforts set the stage for the modernization of mutagenicity testing to protect human and environmental health.
Meet the speakers
Francesco Marchetti
Health Canada/Environmental Health Science Research Bureau /Mechanistic Studies Division
Dr. Francesco Marchetti is a Senior Research Scientist at Health Canada and Adjunct Research Professor at Carleton University. He chairs the Germ Cell workgroup of the Health and Environmental Science Institute’s Genetic Toxicology Technical Committee and is a member of the Organisation for the Economic Co-Operation and Development Expert Group on Genotoxicity Testing. Dr. Marchetti has authored over 125 peer-reviewed publications. He was Editor-In-Chief of Environmental and Molecular Mutagenesis (EMM) during 2012-2016 and serves on the editorial boards of EMM and Mutagenesis. Dr. Marchetti is the current President of the Environmental Mutagenesis and Genomic Society.
Danielle LeBlanc
Health Canada/Environmental Health Science Research Bureau /Mechanistic Studies Division
Danielle LeBlanc is a Biologist at Health Canada under the supervision of Dr. Francesco Marchetti. Danielle completed her undergraduate and Masters work at Carleton University in Ottawa. Danielle is currently focusing on the implementation of Duplex Sequencing for in vivo mutagenesis assessment at Health Canada. In her spare time, she loves to cross-country ski, bake cupcakes and craft cocktails.
