100,000 Genomes Project Rare Disease Programme · 100,000 Genomes Project Rare Disease Programme Dr...

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100,000 Genomes Project Rare Disease Programme Dr Richard Scott Clinical Lead for Rare Disease, Genomics England

Transcript of 100,000 Genomes Project Rare Disease Programme · 100,000 Genomes Project Rare Disease Programme Dr...

Page 1: 100,000 Genomes Project Rare Disease Programme · 100,000 Genomes Project Rare Disease Programme Dr Richard Scott Clinical Lead for Rare Disease, Genomics England ... Report QA Test

100,000 Genomes ProjectRare Disease Programme

Dr Richard Scott

Clinical Lead for Rare Disease, Genomics England

Page 2: 100,000 Genomes Project Rare Disease Programme · 100,000 Genomes Project Rare Disease Programme Dr Richard Scott Clinical Lead for Rare Disease, Genomics England ... Report QA Test

Recruitment to 16th June

210 July 2017

• 31,231 rare disease participants

• Average = 490 participants / week

• Mean family size = 2.3

Page 3: 100,000 Genomes Project Rare Disease Programme · 100,000 Genomes Project Rare Disease Programme Dr Richard Scott Clinical Lead for Rare Disease, Genomics England ... Report QA Test

10/07/2017 3310 July 2017

Rare disease programme

• >200 recruitment categories• Covering >3000 Rare Diseases

• Detailed standardised eligibility

• Prior genetic testing in line with current standard practice

• Core clinical data set:• Disease status• Pedigree data• Human Phenotyping Ontology• Clinical test data where relevant

and not captured by HPO• Using established standards

wherever possible

Page 4: 100,000 Genomes Project Rare Disease Programme · 100,000 Genomes Project Rare Disease Programme Dr Richard Scott Clinical Lead for Rare Disease, Genomics England ... Report QA Test

Patient/ family

Phenotypes & Pedigree

DNA

Genome sequence

Annotated VCFs

Tiered variants

Gene Panel

Variant filtering

Annotation Companies

Review

Gene Panels

Clinical assessment

GeCIP(s)

Validation

Outcomes

Reporting tool

Interpretation pipeline

Report QC

Page 5: 100,000 Genomes Project Rare Disease Programme · 100,000 Genomes Project Rare Disease Programme Dr Richard Scott Clinical Lead for Rare Disease, Genomics England ... Report QA Test

Patient/ family

Phenotypes & Pedigree

DNA

Genome sequence

Annotated VCFs

Tiered variants

Gene Panel

Variant filtering

Annotation Companies

Review

Gene Panels

Clinical assessment

GeCIP(s)

Validation

Outcomes

Reporting tool

Interpretation pipeline

Report QC

Page 6: 100,000 Genomes Project Rare Disease Programme · 100,000 Genomes Project Rare Disease Programme Dr Richard Scott Clinical Lead for Rare Disease, Genomics England ... Report QA Test

Patient/ family

Phenotypes & Pedigree

DNA

Genome sequence

Annotated VCFs

Tiered variants

Gene Panel

Variant filtering

Annotation Companies

Review

Gene Panels

Clinical assessment

GeCIP(s)

Validation

Outcomes

Reporting tool

Interpretation pipeline

Report QC

Gene Panels

Page 7: 100,000 Genomes Project Rare Disease Programme · 100,000 Genomes Project Rare Disease Programme Dr Richard Scott Clinical Lead for Rare Disease, Genomics England ... Report QA Test

Pre-interpretation sign-off

710 July 2017

‘PanelAssigner’

Page 8: 100,000 Genomes Project Rare Disease Programme · 100,000 Genomes Project Rare Disease Programme Dr Richard Scott Clinical Lead for Rare Disease, Genomics England ... Report QA Test

PanelApp

https://panelapp.extge.co.uk/crowdsourcing/PanelApp

https://panelapp.extge.co.uk/crowdsourcing/PanelApp
Page 9: 100,000 Genomes Project Rare Disease Programme · 100,000 Genomes Project Rare Disease Programme Dr Richard Scott Clinical Lead for Rare Disease, Genomics England ... Report QA Test
Page 10: 100,000 Genomes Project Rare Disease Programme · 100,000 Genomes Project Rare Disease Programme Dr Richard Scott Clinical Lead for Rare Disease, Genomics England ... Report QA Test

Patient/ family

Phenotypes & Pedigree

DNA

Genome sequence

Annotated VCFs

Tiered variants

Gene Panel

Variant filtering

Annotation Companies

Review

Clinical assessment

GeCIP(s)

Validation

Outcomes

Reporting tool

Interpretation pipeline

Report QC

Test request

Page 11: 100,000 Genomes Project Rare Disease Programme · 100,000 Genomes Project Rare Disease Programme Dr Richard Scott Clinical Lead for Rare Disease, Genomics England ... Report QA Test

Tiering

1110 July 2017

Page 12: 100,000 Genomes Project Rare Disease Programme · 100,000 Genomes Project Rare Disease Programme Dr Richard Scott Clinical Lead for Rare Disease, Genomics England ... Report QA Test

121210 July 2017

Interpretation at the hospitals

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1. ‘Tiering’– Automated focused initial analysis set up prior to interpretation– Aims to mirror standard diagnostic analysis– ‘Tier 1 or 2' – variants in 0-5 genes within prescribed panel(s)– Non-penetrance pipeline can be run

2. Broader analysis– CIP software allows hospitals further, bespoke analysis– ‘Tier 3’ – standard GeL pipeline but not restricted to gene panels; 20-100s variants– Other tools, dependent on which CIP system

3. Lab-clinical team curate variants and record outcomes– Curations are saved in the central knowledge base– Record clinical impacts of diagnostic result

Tier 1 Tier 2 Tier 3

Singletons 0.2 0.8 497.1

Duos 0.3 0.5 184.1

Trios 0.3 0.5 29.0

Larger 0.4 0.8 27.4

Page 13: 100,000 Genomes Project Rare Disease Programme · 100,000 Genomes Project Rare Disease Programme Dr Richard Scott Clinical Lead for Rare Disease, Genomics England ... Report QA Test

1310 July 2017

From Tiering to MDT…

Guide to Clinical Reporting for Rare Disease, June 2016

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1410 July 2017

From Tiering to MDT…‘Interpretation Request’ and ‘Interpreted Genome’ JSON files

Accessible to NHS GMCs via ‘CIP API’

Guide to Clinical Reporting for Rare Disease, June 2016

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1510 July 2017

From Tiering to MDT…Lists pending/open/closed cases

Links to CIP page for familyCollects outcomes

Access to HTML reports (incl coverage) & other files

Guide to Clinical Reporting for Rare Disease, June 2016

Page 16: 100,000 Genomes Project Rare Disease Programme · 100,000 Genomes Project Rare Disease Programme Dr Richard Scott Clinical Lead for Rare Disease, Genomics England ... Report QA Test

Patient/ family

Phenotypes & Pedigree

DNA

Genome sequence

Annotated VCFs

Tiered variants

Gene Panel

Variant filtering

Annotation Companies

Review

Gene Panels

Clinical assessment

GeCIP(s)

Validation

Outcomes

Reporting tool

Semi-automatedInterpretation pipeline

Report QA

Test request

WORKFLOW MANAGER

DATA DISTRIBUTION FRAMEWORK

Page 17: 100,000 Genomes Project Rare Disease Programme · 100,000 Genomes Project Rare Disease Programme Dr Richard Scott Clinical Lead for Rare Disease, Genomics England ... Report QA Test

Return of results to sites

Reports to date (to 19th June)

• 1988 families (4106 genomes) dispatched to CIPs

• 1741 families (3462 genomes) reports sent to GMCs

• 221 families (467 genomes) outcomes questionnaires completed by GMC labs

• Includes >85% of pilot; status summary to sites for remaining in coming week

Upcoming

• Further batch passing through pipeline now >1000 families

• = ALL of the families with HPO data and no other data issues on GRCh37

• Release to CIPs from mid-July

• Results to GMCs from 1-2 weeks after that (i.e. from late July)

Next steps

• Move to GRCh38 reporting (and with it, CNV calls that we expect to use)

• Move away from batches to even out flow

• Looking at mechanisms to allow GMCs greater control re flow

1710 July 2017

Page 18: 100,000 Genomes Project Rare Disease Programme · 100,000 Genomes Project Rare Disease Programme Dr Richard Scott Clinical Lead for Rare Disease, Genomics England ... Report QA Test

A pipeline for diagnostics

• Major focus of the next year will be validation, QA and accreditation

• This will involve analysis of samples already held as part of the programme

• Plus sequencing of additional positive control samples

• Existing pipeline components• New components, eg STR

Validation, QA and accreditation

Page 19: 100,000 Genomes Project Rare Disease Programme · 100,000 Genomes Project Rare Disease Programme Dr Richard Scott Clinical Lead for Rare Disease, Genomics England ... Report QA Test

Summary

• An overview of the project’s approach to reporting in RD

• An introduction to some of the components that are available to NHS GMCs• Including PanelApp, CIP API and Interpretation portal

• Increased automation is beginning to increase the pace at which reports can be returned to sites• Upcoming batch of >1000 main programme families

• Next steps including• Move to build 38

• Focus of experimental activity to validate pipeline

1910 July 2017

Page 20: 100,000 Genomes Project Rare Disease Programme · 100,000 Genomes Project Rare Disease Programme Dr Richard Scott Clinical Lead for Rare Disease, Genomics England ... Report QA Test

Stay in touch

Follow ‘Genomics England’

www.genomicsengland.co.uk

@genomicsengland #genomes100k

Like the ‘Genomics England’ page


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