TOPMed Site Visit 2018

One day: Thursday, September 13, 2018, 8:30 am - 4:00 pm ?

Perhaps 5 1/2 total hours of presentations.

Draft Agenda

Introduction and Overview of TOPMed data resources and services (30 minutes)

Goncalo Abecasis will present overview of IRC activies

• Introduce IRC personnel and their expertise
• Sequence for 130,000+ participants
• Variant calls and genotypes, phased and unphased
• Structural variant calls in progress
• BRAVO variant browser
• ENCORE analysis server
• TOPMed imputation reference panel
• Main developments in the past year, including security improvements, Manual, etc.

Characteristics of variants in data freeze 6 (20 minutes)

Hyun Min Kang and Jonathan LeFaive will present this section

• Overall numbers
• Differences by ancestry, study and sequencing center
• Allele frequencies of deleterious variants
• Genotype accuracy
• Compare harmonized versus sequencing center mappings
• Process for variant calling, genotyping, filtering, phasing and distribution
• Process for interim 'snapshot' genotypes

Calling structural variants (20 minutes)

Our colleagues at Baylor will present this section. William Salerno?

• Procedures and plans for structural variant calling
• Benefits of ensemble approach
• Initial results
• Data access mechanisms
• Anticipated data size
• Coordination with SNPs and indels

BRAVO variant browser helps to assess variant quality (20 minutes)

Daniel Taliun will present this section

• Purpose
• Which studies are included
• Usage / main features
• Both rare and common variants
• Improvements in the last year
• Access via an applications programming interface (API)
• View all information used in filtering
• Coordination with gnomAD
• Potential plans for PheWeb integration

Summary of contract spending to date (20 minutes)

Denise Bianchi and Goncalo Abecasis will present this section

• Broad subdivisions: personnel, cloud storage, cloud computing, hardware
• Divided between Task 1 and Task 2

Improved results from the latest TOPMed imputation panel (20 minutes)

Goncalo Abecasis will present this, unless Lukas Forer is available. Ketian Yu to prepare summaries of imputation quality

(slides)

• Principle of operation
• Measuring imputation quality in different populations
• Pushing the low frequency boundary
• Improved accuracy for African American and Latino samples
• Challenges and opportunities from collaboration and integration with NIH Commons / NHLBI Stage

Potential Population Genetics Update (20 minutes)

Check with Sebastian Zoellner

Cloud access to TOPMed sequence data (20 minutes)

Tom Blackwell to take the lead on this section

(slides)

• NCBI's 'Fusera' controlled access mechanism
• User perspective -- involves a Google or Amazon billing project
• What is needed for users to have a great overall experience?
• Education and training for users

ENCORE analysis server (20 minutes)

Matthew Flickinger will present this section

• Principle of operation
• Releases only aggregate data summaries
• Visualizations help to assess results
• Data sharing and collaboration tools
• Capability to re-run previous jobs with new data
• SAIGE analysis gives accurate results in case-control studies
• Usage statistics comparing last 12-months to previous 12-months
• Some highlights from user survey results

Manuscript support (30 minutes)

Albert Vernon Smith will present overview for this section

• How can and how is the IRC supporting TOPMed manuscripts and discoveries?

• Overall TOPMed landmark paper
• Analysis of telomere length
• Mitochondrial DNA copy number
• Lipids analysis using TOPMed imputed genotypes
• UK BioBank with TOPMed imputation
• Context specific mutation rates
• Data sharing with Centers for Common Disease Genetics

Interactions with outside groups (30 minutes)

Albert Vernon Smith to take the lead on this section

• NIH Data Commons
• NHLBI Data STAGE
• NHGRI Centers for Common Disease Genetics
• Global Alliance for Genomics and Health (GA4GH)
• NIMH Parkinsons Disease Consortium