The Plan
The overall goal of PREDiSPOSED is to scale the DoBSeq method into clinical use for genomic screening programs of whole populations.
The project is divided into four major phases, and is currently in Phase 1.
Phase 0 proof-of-concept
Prior to the launch of the project, the DoBSeq method was tested at lesser scale. This demonstated full accuracy in both the explorative cohort [10x10 matrix, n = 100, 20 allleles per pool] and the blind validation cohort [10x10 matrix, n = 100, 20 allleles per pool]. Variant detection remained fully sensitive even at 96 samples combined into one pool [1x96 stand-alone, n = 96, 192 alleles per pool], despite low coverage of just 2,000X [11X per allelle]. See publication in Genome Medicine.
Phase 1 scaling and validation
Now we are expanding to a scaled-up matrix design [48x48 matrix, n = 2,304, 96 allleles per pool]. This is expedited by using existing projects' frameworks and/or samples. Current status [updated Nov 2023]:
Scaled batch 1: Being DoBSeq'ed...
Scaled batch 2: Samples being transfered...
Scaled batch 3: Awaiting data approval...
Phase 2 "neonatal screening" of adults
Following validations in Phase 1, the plan is to do genomic screening for variants using Guthrie cards, taken at birth, but of citizens who are now adult and able to consent individually. The ambition is to conduct such screening across 87 matrices [48x48 matrix design, n = 200,448] with reporting of actionable variants. Project is currently awaiting ethical approval for this phase....
Phase 3 expanded neonatal screening
Using experiences and data from Phase 2, the final experimental phase is running an expanded neonatal screening in real time. This setup is subject to substantial revision and fundamental change. Ethical approval for this phase will be sought based on interim data from Phase 2, once available.
Phase 4 clinical implimentation
The final phase is facilitating the experimental design's eventual transition into clinical practice; naturally only for those genetic conditions that have the sufficient evidence-base to do so. This is highly dependant upon the outcome of our project and those of other similar projects.