W11: Determining Genome Variation and Clinical Utility
Tuesday, April 5, 2016 | 12:30 – 4:00 pm

The high data volumes now available via next-generation sequencing have vastly improved researchers’ understanding of genetics and human health. But not all data are equally relevant, for not all genetic variants cause disease. Molecular changes must not only be identified and analyzed across the genome but also properly vetted and interpreted to deliver comprehensible information to physicians and meaningful diagnoses to patients. This workshop explores standards, methods, challenges and solutions that can maximize the utility of genome variant data in clinical settings.

12:30 pm Welcome and Introductions

12:45 Clinical and Personal Utility in Individuals without Active Disease
Liz Worthey, Ph.D., Faculty Investigator & Director, Software Development and Informatics, HudsonAlpha Institute for Biotechnology
Genome-wide sequencing (GWS) is now acknowledged to be the first best molecular diagnostic test under particular circumstances in some clinical settings. It can identify novel or known, pathogenic or likely pathogenic variation associated with rare monogenic disease as well as much (though not all) variation associated with more common and polygenic disease. More recently, GWS has been applied for disease predisposition and risk screening in apparently healthy individuals. This talk examines the strengths and challenges of this approach, exploring the types of information that can be extracted through its application in patients with rare or common disease, and alternatively the clinical and personal utility that can be extracted when it is applied in ostensibly healthy individuals.

1:30 Innovative Partnerships to Create Scalability and Efficiency in NGS Functional Validation
Catherine Brownstein, MPH, Ph.D., Instructor, Pediatrics, Harvard Medical School; Research Associate, Genetics and Genomics, Boston Children’s Hospital; Manager, Molecular Genomics Core Facility
Boston Children’s Hospital has built the infrastructure needed for real-time functional validation via the creation of the BCHx portal. This unique initiative, a partnership between GETTYLAB, the Innovation and Digital Health Accelerator, and the Molecular Genomics Core Facility, assesses real-time availability for functional experiments, allowing laboratories to maximize productivity and clinician scientists to minimize time and cost. Combined with the I2B2 framework that allows for real-time estimates of patient cohorts, and a biorepository to store DNA/tissue samples in concert with genomic data, BCH has created an end-to-end pipeline for validation of variants and genes of unknown significance.

2:15 Refreshment Break

2:45 Drinking from a Firehose: Interpretation of Clinical Whole-Exome/Genome Sequencing
Heather Mason-Suares, Ph.D., FACMG, Associate Laboratory Director, Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine; Instructor, Pathology, Brigham and Women's Hospital
Next-generation sequencing is widely used in molecular diagnostics. Although targeted gene panels remain the standard of care for many monogenic disorders, clinicians are increasingly ordering whole-exome or genome sequencing. But interpreting the large number of variants identified by such sequencing may pose clinical and logistical challenges. This talk addresses current ACMG standards for variant classifications, and also workflow alterations that speed interpretation of variants identified during whole-exome or genome sequencing.

3:30 Interactive Q&A with Instructors and Participants

4:00 Close of Workshop

Instructors

Catherine Brownstein, MPH, Ph.D., Instructor, Pediatrics, Harvard Medical School; Research Associate, Genetics and Genomics, Boston Children’s Hospital; Manager, Molecular Genomics Core Facility

Catherine Brownstein, MPH, Ph.D., is an Instructor of Pediatrics at Harvard Medical School, a Research Associate in Genetics and Genomics at Boston Children’s Hospital, and the Manager of the Molecular Genomics Core Facility. Dr. Brownstein has worked to develop BCH’s research sequencing and pharmacogenomics programs for the past four years, and she has over 10 years of experience in genetics and toxicology, specializing in bone and endocrine disorders. Dr. Brownstein has put her background to use in projects with the Manton Center for Orphan Disease Research, the Developmental Neuropsychiatry Program, the Coordinating Center for the Undiagnosed Diseases Network, and Robert’s Program in Sudden and Unexpected Death in Pediatrics. Her research has elucidated phosphate regulation and the genetic causes of intellectual disability. Before joining BCH in 2011 Dr. Brownstein worked as a toxicologist for the Massachusetts Department of Public Health, and at various startups in Health 2.0.

 Heather Mason-Suares, Ph.D., FACMG, Associate Laboratory Director, Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine; Instructor, Pathology, Brigham and Women's Hospital

Heather Mason-Suares, Ph.D., FACMG, is an Associate Laboratory Director at Partners’ Laboratory for Molecular Medicine, Assistant Laboratory Director for the Cytogenetics Laboratory at Brigham & Women’s Hospital Center for Advanced Molecular Diagnostics, Program Director of the Harvard Medical School Clinical Molecular Genetics Training Program, and an Instructor of Pathology at Harvard Medical School. Dr. Mason-Suares is an ABMGG-certified Molecular Geneticist and Cytogeneticist. Her research and clinical interests concern the application of molecular diagnosis using next-generation sequencing and microarray technologies to chromosomal abnormalities in prenatal cases, RASopathies, cardiomyopathy, and hearing loss. She is currently assisting optimization of ACMG variant classification criteria for the RASopathies as part of a Clinical Genome Resource (ClinGen) initiative.

Liz Worthey, Ph.D., Faculty Investigator & Director, Software Development and Informatics, HudsonAlpha Institute for Biotechnology

Dr. Liz Worthey has degrees in Immunology, Genomics, and Genetics and has studied at leading Universities including Glasgow, Birmingham, Oxford, and Stanford Universities, Imperial College London, and the University of Washington. She has more than 20 years of experience in the development and application of tools, methods, and algorithms to extract knowledge from large genomics and other research and clinical datasets. Dr. Worthey performed the first analyses that successfully used genomic data to change medical treatment and, together with colleagues, built the first Genomic Medicine program in the world. She has been invited to give talks around the world on this topic. At HudsonAlpha she is the head of the Software Development and Informatics (SDI) Group.