`To:
`Subject:
`Date:
`Attachments:
`
`John West
`Christian Haudenschild; Richard Chen; Mark Pratt; Scott Kirk
`Prioritization of Ops Sequencing projects
`Friday, October 12, 2012 7:38:41 AM
`Ops Projects Prioritization JW 11Oct2012.ppt
`
`All,
`
`Following our discussion of the spreadsheet with the Ops projects, I have drafted a proposed
`set of priorities for the sequencing part of the list (attached). This still needs to be followed by
`a priority list on the Pipeline work. Comments are welcome. Let's review on Monday.
`
`Thanks,
`
`John
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`Personalis EX2097
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`
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`Current Ops Projects Prioritization
`Sequencing
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`Draft for discussion
`
`John West
`Oct 11, 2012
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`Personalis Confidential 10/11/2012
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`Personalis EX2097
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`DNA Sequencing Project Priorities
`(Details on following slides)
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`1. Getting the lab set up and basic capabilities demonstrated (mostly done)
`2. Customer projects (Moyamoya & VA-setup)
`3. R&D top priorities:
`•
`Fully modern WGS (sequencing completed)
`•
`Fully modern exomes (almost done)
`• Exome-Plus testing (needs a whole plan)
`4. 1st CLIA Validation (24 CFTR exomes, replicates)
`5. R&D Background projects (run when machine time is available)
`• NA12878 2x250+ & Mainstream diversity panel WES & WGS
`6. CLIA Menu expansion to include WGS (w/ mainstream diversity panel ?)
`7. R&D lower priorities:
`• Known pathogenic STR variant samples
`• Personalis-custom assays (pulsed field gel, phasing)
`• Accuracy dependence on sequencing operation parameters
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`Personalis Confidential 10/11/2012
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`Personalis EX2097
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`Getting the lab set up and basic capabilities demonstrated
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`• Phi-X qualifying runs
`– Completed on both machines
`• Whole genome sequencing
`– Good data from 8 lanes of NA12878 already completed
`– Further WGS lab optimization on other projects
`• Exome capability demonstrated
`– Pullout looks OK on MiSeq
`– 1st run on HiSeq failed turn-around
`– 2nd run on HiSeq now, with 24 including CEPH family, Venter
`• Establish data connection from machine output to HugeSeq pipeline
`– Casava ? done ?
`• Upgrade HiSeq(s) to HS-2500 (Jan 2013 ?) & then validation run(s)
`• Upgrade MiSeq to dual surface imaging (Date TBD) & then validation run
`• Other ?
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`Personalis Confidential 10/11/2012
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`Customer Projects
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`• Moyamoya
`– 1st samples running now
`• Getting set up for VA
`– Many items on R&D’s current priority list
`– Hardware needs meeting this morning
`– Employee fingerprinting, etc
`– Christian to complete this list
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`Personalis Confidential 10/11/2012
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`R&D Top Priorities
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`• Fully modern WGS (sequencing completed)
`– v3 sequencing chemistry, PCR-free, gel-free, HiSeq run
`– Data is for A/B, MIE and single-genome error characterization
`– These also provide the WGS for WGS / exome / E+ comparisons
`– NA12878 we sequenced ourselves (8 lanes on HiSeq)
`– CEPH1463 family & Venter seq for us to 60x by ILMN
`– On pipeline runs, prioritize the replicates (NA12878 & Venter, for A/B comparisons
`– Have we defined the Pipeline version for this ? NEMAR ?
`• Fully modern exomes (sequencing almost done)
`– v3 sequencing chemistry, ILMN pullout, can’t be PCR-free
`– Data is for coverage statistics & other “normal ranges” for QC report
`– These also provide the exomes for WGS / exome / E+ comparisons
`– Data can be used for A/B comparison of same sample & pullout sequenced twice, but does
`not include same sample with two separate library preps & pull outs (for that see CLIA
`validating CFTR exomes)
`• Exome-Plus testing
`– Mark is developing a whole project plan & wants to review it
`– First round pullout kits are due in about 3 weeks
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`Personalis Confidential 10/11/2012
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`1st CLIA Validation
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`24 samples with independently characterized CFTR mutations
`•
`• Exome sequence with replicates of:
`– Library prep
`– Pullout
`– Sequencing
`• Consider running each flow cell with an NA12878 exome as a control, esp
`for SV / CNV detection from exomes
`• This data set is also of interest to R&D to understand exome variability &
`reproducibility
`• For CLIA, the work must be performed by a CLS, start date : 10/22
`• We will need to define pipeline version to run, etc
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`Personalis Confidential 10/11/2012
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`R&D Background Projects
`Run when machine time is available
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`• NA12878 2x250+ full coverage WGS
`•
`Data is for our Gold-standard genome
`• Must be run on MiSeq to get these read lengths
`• May take 30-40 sequencing runs to accumulate enough coverage
`•
`Several runs have been completed so far
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`Test data set for approaches to alignment with reads >200 bases
`• Max 3 runs / week if MiSeq used full time
`•
`Shujun is experimenting with exact read lengths, likely to be asymmetrical (e.g. 275 / 250)
`It may be helpful to have a range of insert lengths in this data set
`•
`•
`Shujun may experiment with insert lengths 1-3 kbp
`• Mainstream diversity panel WES & WGS
`– 7-8 mainstream but diverse ethnicities, 24 samples, DNA received from Coriell
`– This is to be an ethnically more diverse reference set for us, to parallel the work we have
`done on the European CEPH1463 pedigree
`– 24 exomes on HiSeq first (one flow cell)
`• Run with NA12878 as an exome control ?
`– Then 30-40x WGS as machine time is available (use for CLIA menu expansion to WGS ?)
`– These are also candidates for Exome+ testing
`– What Pipeline version ? NEMAR ?
`Personalis Confidential 10/11/2012
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`CLIA Menu Expansion to Include WGS
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`• Overlap with WGS of mainstream diversity panel ?
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`Personalis Confidential 10/11/2012
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`R&D Lower Priorities
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`• Known pathogenic STR variant samples
`– These may be pulled forward as part of the Exome+ pullout testing,
`likely with long-read set, run on MiSeq
`• Accuracy dependence on sequencing operation parameters
`– Some of this is being explored on the MiSeq for the Gold-Standard
`genome (NA12878 2x250+) and Exome+ pullouts
`• Read lengths (asymmetrical)
`• Insert lengths (how far can we go, particularly with pullouts ?)
`• Optimization for pullout of high GC set
`• Personalis-custom assays (pulsed field gel, phasing)
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`Personalis Confidential 10/11/2012
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`Personalis EX2097
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