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On April 19-20, 2016, the National Human Genome Research Institute (NHGRI) sponsored its ninth Genomic Medicine meeting - Genomic Medicine IX: Bedside to Bench - Mind the Gaps  - at the Sheraton Silver Spring Hotel in Silver Spring, Maryland.

GM9 focused on facilitating bedside back to bench research by focusing on one of the most vexing problems in clinical sequencing: characterizing and interpreting variants of uncertain significance (VUS).

Objectives included to:

  1. Review examples of successful interactions between basic scientists and clinical genomicists and explore what made them successful;
  2. Identify ways to enhance interactions between basic scientists and clinical genomicists (aka, the virtuous cycle of bench to bedside and back again);
  3. Determine how better to integrate basic science research efforts with clinically important questions, to enhance the exploration of clinical implications of basic discoveries.

Topic areas covered:

  • How basic science lends insights into disease mechanisms to facilitate effective approaches for understanding the function of VUS and relevance to disease mechanisms.
  • Computational and informatics approaches to prediction and annotation of genomic variant function.
  • Efforts and strategies for data integration through the development and implementation of biomedical ontologies.
  • Facilitating bedside-back-to-bench research.

Tuesday, April 19, 2016

  Topic Speaker
Session 1: Introduction, Background
Dan Roden, Moderator
8:30 a.m.

Welcome, Introductions, and Goals of the Meeting
 Video (Manolio) |  Video (Bult) |  Video (Green)
 Video (Around the Room Introductions)  | Slides 

Carol Bult
Eric Green
Teri Manolio
8:50 a.m.

Convincing Clinicians to Use Functionalized Genomic Information
 Video | Slides 

Howard Jacob
9:05 a.m.

Magnitude of the Problem - Basic Science Perspective on Need for Integration
 Video | Slides 

Monte Westerfield
9:30 a.m.

Magnitude of the Problem - Clinical Perspective on Need for Integration
 Video | Slides 

Gail Herman
9:55 a.m. Discussion
10:40 a.m. Break
Session 2: Vexing Clinical Problems Needing Basic Input
Laura Rodriguez
, Moderator
11:00 a.m.

Speeding Functional Assessment to Benefit Patients
 Video | Slides 

Stephen Kingsmore
11:20 a.m.

De Novo Variants that Inform Clinical Phenotypes
 Video | Slides 

Christine Seidman
11:40 a.m. Discussion
12:25 p.m. Lunch
Session 3: From Variant to Disease Mechanisms - Specific Examples of How Model Systems have used Genetic / Genomic Approaches to
Lend Insight into Human Disease that had Clinical Relevance
Howard Jacob, Moderator
1:30 p.m.

Integrating Model Organism Data around Clinical Genomics
Video | Slides 

Calum MacRae
1:50 p.m.

Leveraging Congenital Heart Disease Mouse Model Findings to Improve Clinical Outcome
Video | Slides 

Cecilia Lo
2:10 p.m. Discussion
3:00 p.m. Break
Session 4: Computational Approaches to Variant Function Prediction Methods for
Predicting Functional Consequences of Variants
Marc Williams, Moderator
3:20 p.m.

Leveraging Massive-Scale Databases of Human Genetic Variation
Video | Slides 

Daniel MacArthur
3:40 p.m.

Empowering Variant Effect Prediction with Large Scale Mutagenesis Data
Video | Slides



Douglas Fowler
4:00 p.m. Discussion
4:45 p.m. Panel 1: Topics to be defined based on Day 1 sessions
Teri Manolio, Moderator
Leslie Biesecker
Gregory Cooper
Cathleen Lutz
Erin Ramos
Liz Worthey
5:45 p.m. First Day Summary and Discussion Carol Bult
Teri Manolio
6:00 p.m. Adjourn

Wednesday, April 20, 2016

Time Topic Speaker
Session 5: Functionalizing VUS's
Howard McLeod, Moderator
8:30 a.m.

Massively Parallel Functional Analysis of Missense Mutations In BRCA1 for Interpreting Variants of Uncertain Significance
Video | Slides

Lea Starita
8:50 a.m.

CRISPR-Cas9 Mediated Mouse Model Creation and Transcription Regulation
Video | Slides 

Haoyi Wang
9:10 a.m. Discussion
9:55 a.m. Break
Session 6: Biomedical phenotype ontologies and data integration
Carol Bult, Moderator
10:15 a.m.

Translating Human to Models and Back Again: Phenotype Ontologies for Data Integration and Discovery
Video | Slides

Melissa Haendel
10:35 a.m.

Data Integration: Genome X Transcriptome X EMR
Video | Slides

Nancy Cox
10:55 a.m. Discussion
11:35 a.m.

Making Sausage
Video | Slides

Robert Nussbaum
12:00 p.m. Working Lunch
1:00 p.m. Panel 2: Topics to be defined based on Day 2 sessions
Rex Chisholm, Moderator
Calum MacRae
Jose Ordovas
Peter Robinson
Wendy Rubinstein
Barbara Stranger
2:00 p.m. Summary Discussion: Promoting Bedside-Back-to-Bench Research
  • Prioritizing variants for functional/mechanistic investigation
  • Incentivizing demonstrations of benignity
  • Engaging industry
Video | Slides
Carol Bult
Teri Manolio
3:30 p.m. Next Steps
Carol Bult
Teri Manolio
4:00 p.m. Adjourn

Last updated: April 19, 2016