Analytical Validity Working Group

The Analytical Validity working group is focused on best practices for the analytical validation of clinical WGS for the diagnosis of germline genetic disease. This includes defined analytical metrics and thresholds for clinical WGS that enable no loss in performance compared to whole exome sequencing (WES) and chromosomal microarray (CMA).

Working Group Participants:

• Project Lead: Christian Marshall (SickKids)
• Coordinator: Stacie Taylor (Illumina)
• Niall Lennon, Steven Harrison, Matt Lebo (Broad Institute of MIT and Harvard)
• Hutton Kearney, Eric Klee, Ross Rowsey (Mayo Clinic)
• James Stavropoulos (SickKids)
• Shashikant Kulkarni, Pengfei Liu (Baylor Genetics)
• Ryan Taft, John Belmont (Illumina)
• Shimul Chowdhury (Rady Children’s)
• Jillian Buchan (Stanford Medicine)
• David Bick (HudsonAlpha)
• Vaidehi Jobanputra (NYGC)

Clinical Utility & Usefulness Measures Working Group

The Clinical Utility & Usefulness Measures working group is focused on best practices to assess the clinical utility of clinical WGS for the diagnosis of germline genetic disease, by defining the dimensions of clinical utility and emphasizing objective and validated measures. A focus will be placed on defined measures which are most important to different stakeholders and empiric strategies for measuring each dimension.

Working Group Participants:

• Project Lead: Robin Hayeems (SickKids)
• Coordinator: Stacie Taylor (Illumina)
• David Dimmock (Rady Children’s)
• Shashikant Kulkarni (Baylor Genetics)
• John Belmont (Illumina)
• Roberto Mendoza (SickKids)
• David Bick (HudsonAlpha)
• Robert Green (Broad Institute of MIT and Harvard)
• Brendan Lanpher (Mayo Clinic)
• Euan Ashley, Megan Grove (Stanford Medicine)

Clinical Data Aggregation, Infrastructure & Sharing Working Group

The Clinical Data Aggregation, Infrastructure & Sharing working group is focused on best practices for the management, sharing and aggregation of clinical WGS data. This topic includes the unique challenges of the management of data infrastructure that enables optimal data usage and sharing within a clinical diagnostic laboratory setting.

Working Group Participants:

• Project Co-Lead: Christian Marshall (SickKids)
• Project Co-Lead: Michael Zody (NYGC)
• Coordinator: Stacie Taylor (Illumina)
• Laura Gauthier, Niall Lennon (Broad Institute of MIT and Harvard)
• Euan Ashley (Stanford Medicine)
• Christian Marshall, Ryan Yuen, Stephen Scherer, Joe Whitney (SickKids)
• Mathieu Wiepert, Zhiyv Niu (Mayo Clinic)
• Brian Lajoie, John Belmont, Alison Coffey (Illumina)

Test Interpretation and Reporting

The Test Interpretation and Reporting working group is focused on best practices and practical guidance for the analysis and reporting of clinical WGS in the context of germline genetic disease diagnosis. This includes phenotype capture, data annotation, variant filtration and prioritization strategies, content and structure of WGS reports, and WGS reanalysis.

Members:

• Project Co-Lead: Christina Austin-Tse (Broad Institute of MIT and Harvard)
• Project Co-lead: Vaidehi Jobanputra (NYGC)
• Co-Senior author: Heidi Rehm (Broad Institute of MIT and Harvard)
• Co-Senior author: Hutton Kearney (Mayo clinic)
• Coordinator: Stacie Taylor (Illumina)
• David Bick (HudsonAlpha)
• Shashikant Kulkarni (Baylor)
• Kasia Ellsworth (Rady Children’s)
• Sarah Barnett, Nicole Boczek, Cherisse Marcou (Mayo clinic)
• Elizabeth Spiteri (Stanford)
• Edwin (Ted) Young (SickKids)
• Denise Perry, Ryan Taft, John Belmont (Illumina)