Date post: | 11-May-2015 |
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Technology |
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1/21Copyright 2013 InVitae, Inc
Reece Hart, [email protected]
InVitae, Inc.invitae.com
Developing a Clinical Genome Developing a Clinical Genome Interpretation Pipeline at AWSInterpretation Pipeline at AWS
2/21Copyright 2013 InVitae, Inc
The MissionThe MissionTo provide comprehensive,
clinically-relevant information from genomic variation data in a single test.
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one sampleone requisition
one reportup to 264 conditions
two weeksone lab, one price
InVitae's process features online requisitioning and reporting, CLIA-certified sequencing, and a HIPAA-compliant information management.
intakeRequisitioning and Laboratory Information Management System
interpretationsequencing review
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Where does InVitae fit?Where does InVitae fit?
photos:Baylor College of Medicine, Univ. Utah, learningradiology.com, sciencephotos.com
Patient presents with symptoms
If genomic interpretation might influence diagnosis or treatment, doctor refers patient to genetic counselor
GC takes history; sample is sent to internal or one of hundreds of labs that provide specific genomic tests
Sequencing and other lab data are processed into
preliminary iterpretation
Report is returned to GC and/or physician who
verify interpretation and consult with patient
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http://www.ncbi.nlm.nih.gov/sites/GeneTests/
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Examples of published clinical variantsExamples of published clinical variants
➢ Inherited conditions● NM_000136.2:c.355_360delATGAGAinsT
‒ at risk for Fanconi Anemia
➢ Carrier conditions● NM_000520.4:c.1277_1278insGATA
‒ carrier for Tay-Sachs
➢ Pharmacogenetic conditions● HLAB*1502 & HLAB*5701 haplotypes (23 snps)
‒ Abacavir drug-induced hypersensitivity‒ Flucloxacillin drug-induced liver injury‒ Carbamazepine drug-induced cutaneous adverse events
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Reported VariantsReported Variants
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Our ReportOur Report
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NOW
Early AccessCommercial Program
(CLIA Certified)
264GENETIC TESTS
$1,5002014
Goal to update offeringevery six months
>1000GENETIC TESTS
<$1,000
50x minimum, ~425x average100% coverage of curated variants>90% of targeted regionsSNVs, indels (<100nt), VUS
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How?How?By deeply integrating custom genetic
curation, sequencing assay design, and analytical pipelines.
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Curation + Assay Design + PipelineCuration + Assay Design + Pipeline
curation
analysis pipeline
A>T
sequence assay
curation
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Protected Health Informationon-site, encrypted, restricted access
Architectural OverviewArchitectural Overview
IPSecTunnel
4.5GB up4 MB down
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Pipeline OverviewPipeline Overview
aligned readsreads
variantsaligned reads
reportvariants
bwasamtoolsgatkpicard
+ assay regions
+ GRCh37 ref+ 1kg known indels
gatkfreebayescustom variant calling
+ qualities
+ metrics
+ quality metrics
call haplotypesmatch variantsVUS pipelinerender
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AWS TopologyAWS Topology
1 VPC3 subnets
NFS
interactive hostsweb services
scaled dynamically
build/test
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What's worked well at AWS?What's worked well at AWS?
➢ Performance and Capacity Scaling● on-demand
➢ Security and VPG● Simple, comprehensive rules for VPCs
➢ Service ecosystem: EC2, EBS, S3, R53, IAM, VPC● boto!
➢ Future:● Archive: S3 and Glacier?● Investigate workflows ● Reanalysis
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What challenges have we experienced?What challenges have we experienced?
➢ Large shared fileystems● poor and variable performance (better now)● familiarity, flexibility, transparency● existing software expectations
➢ Node failures● Once upon a time... 0-3 times per day, no warning● moved zones no longer an issue
➢ Devops● Built our own, but moving to puppet
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One source of variation...One source of variation...
attribution unknown
21/21Copyright 2013 InVitae, Inc