Shifting the Paradigm for Genetic Sample Resources

Shifting the Paradigm for Genetic Sample ResourcesJ. Claiborne Stephens, CEO, Genomics GPSRon Bromley, Ena Bromley, BSSITed Kalbfleisch, Intrepid BioInformaticsDisclaimerGenomics GPS is focused on the strategic application of genomic studies, samples, and analyses in a variety of commercial applicationsClay Stephens, Founder and CEO, is currently the only employeeOverviewCurrent ProcessProposal for ChangeContrastScientific Benefits of New ModelCommercial BenefitsDiscussionGenetic BiosamplesTypically bloodTreated for clottingAntimicrobialFrozenExtracted DNAFrozenBlottedDesired dataGenotype or sequence of one or more lociCurrent ModelSample isTaken and prepped for storageRetrieved and prepped for genotypingGenotypedRemainder returned to storage

Data obtained

Inventory (where is it, how much is left, what format is it in)

Proposed ModelSampleTaken and prepped for genotypingUniformly genotyped and imputedNote: combination of direct and indirect methodsRemainder sent to storage (archival)

Data obtained

Inventory (where is it, how much is left, what format is it in)

PositivesFamiliarNo upfront genotyping expenseObtain only the data desiredGenotyping/sequencing costs continue to drop

NegativesPossibility that sample gets lost or consent expiresExpense in storing/retrieving/ prepping sampleTime lag in aboveNo/Limited use of sampleNon-uniform data generated

Pros and Cons of Current ModelPositivesData available and uniformReduced expense for storing/ retrieving/prepping sampleReduced time lag in aboveMaximize use of sampleSample loss avoided Data may improve over time as reference panels and imputation algorithms improveNegativesUpfront genotyping expenseMay still miss the desired data (e.g., sequence)Infrastructure for data maintenance and access may be lacking

Pros and Cons of New ModelPerfect Genomic DataComplete and accurate full sequenceIncluding simple structural (indel) variationIncluding complex structural variation (CNV)Including phase

ExclusionsMosaicismEpigenetic phenomenaWhat is Sacrificed in Proposal?de novo mutations (single patient)Private variation (single family)Rare variants that fail to imputeCommon variants that fail to imputeIndels and CNVs that fail to impute

Phase should be accessible as part of imputation processCommercial ConsiderationsPer SampleIncurring upfront genotyping costs in place of sample prep/storage/retrieval costsStorage and retrieval is now data, not sample

InfrastructureFreezers and personnel now minimized to storage of archival (non-frozen?) samplesShift to data infrastructureDiscussionThanks!The End(s)