From:
`To:
`Subject:
`Date:
`Attachments:
`
`Richard Chen
`John West; Carol Tillis; Christian Haudenschild; Eliane Sousa; Richard Chen
`Final Board Slides
`Tuesday, September 4, 2012 4:32:56 PM
`board.09.05.12.v9.roc.ppt
`
`Ready for Printing....
`
`Personalis EX2083
`
`

`

`Product Development
`
`Personalis, Inc.
`09.05.2012
`
`Richard Chen, CSO
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`1
`
`Personalis EX2083
`
`

`

`Product Development Overview
`
`• Product
`– Prototype
`– Early Customers/Collaborations
`– Product Features, Deliverables, and Differentiation
`• Content Development
`• Computing Infrastructure
`• Hiring
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`2
`
`Personalis EX2083
`
`

`

`Product Roadmap
`
`Genome Interpretation Service (GIS)
`
`What are the disease risks?
`Which drugs should be avoided
`or dosed differently?
`
`Disease Variant Discovery Service (DVDS)
`
`What is the causative
`Genetic Variant?
`
`Personalis Genome Services (PGS)
`
`Sample Collection &
`DNA Extraction
`
`TTAGC…
`Whole
`Genome/Exome
`Sequence
`
`Alignment and
`Variant Calling
`
`Genes
`
`Pathways &
`Networks
`Diseases
`
`Drugs
`
`Genome Pipeline
`Services Renamed
`Personalis
`Genome Services
`to reflect broad
`nature of the
`solution
`
`Clinical
`Research
`(IRB)
`Growing clinical
`opportunity
`
`Discovery
`Research
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`3
`
`Personalis EX2083
`
`

`

`Personalis Genome Services: Prototype
`Prototype Ready for Testing with Customers
`
`• Achieved August delivery Milestone for Prototype Service.
`– In past 3-4 months of development. Four sprints, 545 tasks/features completed
`– Moved and set up infrastructure for Confluence, Jira, Git, went from 80 to over 350 cores, more
`than doubled storage capacity to >300 TB of storage
`– Tested internally: 25 genomes in 25 days
`– All prototype components functional & developer tested
`– Able deliver prototype despite hiring challenges
`
`•
`
`•
`
`Prototype goal: Do enough product development to:
`– Evaluate overall value proposition
`– Test our process for delivering the service
`– Provide early feedback for v1 product, Generate some early revenue
`– Prototype type is not yet optimized for performance, scalability, usability, visualization
`
`Planning process for v1 of PGS includes balancing multiple new priorities:
`– New laboratory efforts including building Exome+ offering are critical for product differentiation
`but resource intensive
`– Working with early customers/collaborations such as the Moyamoya
`– Key differentiators for v1 also include improved SV detection, Improved graphics/visualization,
`new analytics
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`4
`
`Personalis EX2083
`
`

`

`Personalis Genome Services
`Moyamoya project: Typical Case-Control Study
`
`•
`
`•
`
`First customer: Moyamoya study with Dr. Gary Steinberg @ Stanford
`– Genetic disease of unknown cause resulting in early onset strokes and seizures
`– Caused by blockage of key vessels in the brain resulting in collateral development
`– Phenotypically heterogeneous: Can be isolated or seen in conjunction with neurocutaneous
`syndromes, Down’s syndrome, etc.
`Typical case-control customer:
`– 130 cases of Moyamoya, would like to understand genetic cause
`– clinical expert with patient samples
`– limited bioinformatics capability
`– no controls
`• R&D involved in designing & executing these early projects, enabling rapid
`feedback loop into development for v1
`– We will provide and end-to-end solution consisting of exome sequencing, alignment, variant
`calling, annotation, case-control analysis
`– Use gender and ethnicity matched controls from 1000 genomes
`– Will do subgrouped analysis based on different phenotypes
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`5
`
`Personalis EX2083
`
`

`

`Personalis Genome Services
`
`Inaccuracies in current sequencing solutions lead to incorrect conclusions/false leads that result in
`increased cost and time for researchers and clinicians, poor outcomes for patients
`
`Personalis Aims to Provide the Most Comprehensive, Accurate, End-to-End Genome Service Available Today
`
`Sequencing
`
`Pipeline
`
`Annotation
`
`Analytics
`
`Sample Prep
`
`Sequencing
`
`Alignment
`
`Variant
`Discovery
`
`Proprietary DB
`Annotation
`
`Public DB
`Annotation
`
`QC Reports
`
`Analysis &
`Interpretation
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`6
`
`Personalis EX2083
`
`

`

`Personalis Genome Services
`Components of our Service Planned for Version 1.0
`
`Sequencing
`
`Pipeline
`
`Annotation
`
`Analytics
`
`Sample Prep
`
`Sequencing
`
`Alignment
`
`Variant
`Discovery
`
`Proprietary DB
`Annotation
`
`Public DB
`Annotation
`
`QC Reports
`
`Analysis &
`Interpretation
`
`Standard Alignment and Variant
`Calling Pipeline
`Custom Alignment and Variant
`Calling Pipeline
`
`Exome Sequencing
`
`Exome Plus Sequencing
`
`WGS Plus Sequencing
`
`CLIA Sequencing
`
`Varimed DB (Proprietary)
`
`Disease Case-Ctrl Study
`
`PharmGKB (Proprietary)
`
`Population Case-Ctrl Study
`
`Mendel DB (Proprietary)
`
`Regulome (Proprietary)
`
`Patient Stratification Case-Ctrl
`Study
`Pharmacogenomics Case-Ctrl
`Study
`
`30+ Public DB
`
`Tumor vs Nrml Case-Ctrl Study
`
`Mendelian Multiple Trios Study
`
`Mendelian Large Pedigree Study
`
`Rare Pediatric Syndromes Dx
`(Trio etc)
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`7
`
`Personalis EX2083
`
`

`

`PGS Prototype
`PGS Version 1.0
`Sequencing
`
`Personalis Genome Services
`Prototype vs Version 1.0 Features
`
`Pipeline
`
`Annotation
`
`Analytics
`
`Sample Prep
`
`Sequencing
`
`Alignment
`
`Variant
`Discovery
`
`Proprietary DB
`Annotation
`
`Public DB
`Annotation
`
`QC Reports
`
`Analysis &
`Interpretation
`
`Standard Alignment and Variant
`Calling Pipeline
`Custom Alignment and Variant
`Calling Pipeline
`
`Exome Sequencing
`
`Exome Plus Sequencing
`
`WGS Plus Sequencing
`
`CLIA Sequencing
`
`Varimed DB (Proprietary)
`
`Disease Case-Ctrl Study
`
`PharmGKB (Proprietary)
`
`Population Case-Ctrl Study
`
`Mendel DB (Proprietary)
`
`Regulome (Proprietary)
`
`Patient Stratification Case-Ctrl
`Study
`Pharmacogenomics Case-Ctrl
`Study
`
`30+ Public DB
`
`Tumor vs Nrml Case-Ctrl Study
`
`Mendelian Multiple Trios Study
`
`Mendelian Large Pedigree Study
`
`Rare Pediatric Syndromes Dx
`(Trio etc)
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`8
`
`Personalis EX2083
`
`

`

`PGS Prototype
`PGS Version 1.0
`Sequencing
`
`Personalis Genome Services
`Prototype vs Version 1.0 Features
`
`Pipeline
`
`Annotation
`
`Analytics
`
`Sample Prep
`
`Sequencing
`
`Alignment
`
`Variant
`Discovery
`
`Proprietary DB
`Annotation
`
`Public DB
`Annotation
`
`QC Reports
`
`Analysis &
`Interpretation
`
`Exome Sequencing
`
`Exome Plus Sequencing
`
`WGS Plus Sequencing
`
`CLIA Sequencing
`
`• Moyamoya project
`Standard Alignment and Variant
`• Stanford AAA project
`Varimed DB (Proprietary)
`Calling Pipeline
`• UCSB Alzheimer’s project
`Custom Alignment and Variant
`• ALS project
`PharmGKB (Proprietary)
`Calling Pipeline
`
`Mendel DB (Proprietary)
`• 1 Million VA Genomes project
`
`Regulome (Proprietary)
`• Genentech crenezumab trial
`30+ Public DB
`• Warfarin response study
`
`Disease Case-Ctrl Study
`
`Population Case-Ctrl Study
`
`Patient Stratification Case-Ctrl
`Study
`Pharmacogenomics Case-Ctrl
`Study
`
`Tumor vs Nrml Case-Ctrl Study
`
`Mendelian Multiple Trios Study
`
`Mendelian Large Pedigree Study
`
`Rare Pediatric Syndromes Dx
`(Trio etc)
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`9
`
`Personalis EX2083
`
`

`

`Personalis Genome Services
`Significantly Differentiated at Each Step
`
`Sequencing
`
`Pipeline
`
`Annotation
`
`Analytics
`
`Sample Prep
`
`Sequencing
`
`Alignment
`
`Variant
`Discovery
`
`Proprietary DB
`Annotation
`
`Public DB
`Annotation
`
`QC Reports
`
`Analysis &
`Interpretation
`
`•
`
`•
`
`•
`
`Exome and WGS with
`optimized sample prep
`for improve
`performance over
`problematic regions of
`the genome
`
`Exome Plus capability
`improves accuracy and
`extends exomes to
`biomedically important
`non-coding regions
`
`CLIA sequencing
`capability for clinical
`grade exomes or whole
`genomes
`
`• State of the art alignment
`pipeline implementing
`best of breed algorithms
`resulting in better
`alignments, tested and
`optimized for accuracy
`and performance
`
`• Personalis enhanced and
`corrected reference
`genome for improved
`alignment and accuracy
`
`•
`
`Improved variant
`(SNP/Indel/SV) calling
`through integration of
`orthogonal methods to
`improve accuracy
`
`• Four high-quality,
`detailed, manually
`curated proprietary
`databases that enable
`genome annotation and
`analysis of complex
`disease, Mendelian
`disease,
`pharmacogenomics, and
`regulatory regions
`
`• Comprehensive genome
`annotation integrating and
`managing data from over
`30 public databases
`
`• Cutting edge proprietary
`analytics engine for case
`control analysis reveals
`statistically significant
`enrichment of genes,
`pathways, and diseases
`
`• Analytics powered by
`proprietary databases
`
`• Proprietary
`family/pedigree analysis
`and filtering methods
`
`• Comprehensive QC
`reporting for better
`accuracy assessment
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`10
`
`Personalis EX2083
`
`

`

`Personalis Genome Services: Sequencing
`Personalis Sequencing Improves Problematic Regions and Medically
`Intepretable Regions of the Genome
`
`Problem: Segmental Duplications
`•
`7% of exome is in segmental
`duplications leading to ambiguous
`alignments, phantom variants and
`missed calls
`Personalis solution:
`•
`Supplement exome with long paired
`reads (2x250) in regions having high
`identity segmental duplications.
`Longer reads improve alignment and
`subsequent sequence determination
`
`•
`
`Problem: Repeat Expansion Disorders
`•Repeat Expansion Disorders (e.g.
`Huntington’s) are problematic for short
`read sequencing. Clinical interpretation
`requires accurate repeat length
`determination
`Personalis solution:
`•Supplement exome with long paired
`reads (2x250) anchored to interpretable
`expanding repeat region flanks
`•Use high coverage spanning reads to
`correctly genotype region
`
`Personalis
`Exome
`
`Personalis
`Exome +
`
`Personalis
`WGS
`
`Personalis
`CLIA Seq
`
`•
`
`Problem: Low Coverage Regions
`•
`Some areas of the genome (or exome) are
`underrepresented in NGS because of
`process biases, e.g. high GC content
`Low coverage tends to drive genotyping
`errors
`Personalis solution:
`•
`Supplement genome (or exome) with
`targeted libraries supplementing
`systematically low coverage in areas of
`medical interest
`Enriching weak spots is more effective
`(and economical) than just pushing up
`average coverage
`
`•
`
`Problem: HLA
`•
`HLA is poorly addressed with NGS and
`standard analysis
`•
`Complex repeat structure
`•
`Typing requires phasing / haplotyping
`Personalis solution:
`•
`Develop targeted longer read library linking
`critical variant loci
`Develop or acquire haplotype-based typing
`analysis pipeline
`
`•
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`11
`
`Personalis EX2083
`
`

`

`Personalis Genome Services: Pipeline
`Personalis Pipeline Solves Critical Problems that Hinder Other Approaches
`
`Problem:
`Over 15 public and
`proprietary algorithms to
`integrate, keep up to date,
`test and maintain. E.g. GATK
`2.0 bug with recalibration
`detected by Personalis
`
`Personalis Solution:
`Systematic update, testing
`procedures and dedicated
`accuracy team to ensure
`integrity of various
`components
`
`Problem:
`Minor alleles in the public
`reference result in medically
`interpretable variants being
`missed. E.g. Factor V Leiden
`would be missed using
`current reference
`
`Personalis Solution:
`Corrections to public
`reference enabling better
`alignments and variant calls
`
`9/5/12
`
`Read
`Mapping
`
`Quality
`Enhancement
`
`Variant
`Characterization
`
`Problem:
`Ethnicity differences not
`accounted for in aligning to
`public reference
`
`Personalis Solution:
`Personalis corrections to
`public reference enabling
`better alignments
`
`Problem:
`Zygosity of SV’s not reported by
`conventional pipelines resulting in
`poor interpretability for clinical
`impact
`
`Personalis solution:
`Personalis pipeline proprietary
`algorithm for detecting SV with
`reference calls, breakpoints and
`zygosity.
`Personalis, Inc. Proprietary and Confidential
`
`Problem:
`Lam et. al. Nature Biotech
`12% discordance for SNPs
`73% discordance for indel’s
`between platforms
`
`Personalis solution:
`Combining results of
`orthogonal SNP and SV
`detection algorithms to
`improve accuracy
`One of the algorithms
`invented by Personalis
`scientist
`
`Problem:
`SV’s such as Indels, Long
`Indels, STRs, CNV’s poorly
`detected using conventional
`methods
`
`Personalis solution:
`New algorithms for improving
`detection
`Laboratory optimization to
`enhance ability to detect
`
`12
`
`Personalis EX2083
`
`

`

`Personalis Genome Services: Annotation
` Problems with Existing Databases as a Primary Source of Annotations
`
`•
`
`Problem: Accuracy Of Existing Databases
`•
`Estimated 25% of variants in HGMD are not
`pathogenic
`Personalis analysis suggests many of the
`variations in OMIM are present at high MAF
`(>35%) bringing into question their validity
`(ex MSUD, Sandhoff, etc)
`Personalis solution:
`•
`Personalis has a high quality, manually
`curated proprietary variant, Mendelian, and
`PGx database
`Automated cross checking between
`proprietary and public DB sources enables
`error correction
`
`•
`
`Problem: Primary Source Errors
`•Even published literature can harbor errors
`•E.g. Original reports on causative alleles for
`multiple Mendelian disorders were incorrectly
`assigned because of the presence of the minor
`allele in the public reference.
`•E.g. COMP and MMAB: discrepancy between
`tables within GeneReviews (pathogenic) and
`descriptive text and/or allele freq. (polymorphic)
`Personalis solution:
`•Personalis’ Mendel DB uses manual QC to catch
`and correct errors in primary sources
`
`Problem: Public DB’s have Large Gaps in
`Coverage
`•As a matter of practice, many public DB’s such as
`OMIM don’t attempt to systematically curate
`disease causing variants
`•Many causative variants are missing from OMIM
`•HGMD has no pathogenicity scores
`Personalis solution:
`•Personalis is systematically cataloguing variants
`for the most common Mendialian phenotypes
`
`Problem: Public DB’s have variants incorrectly
`mapped to reference genome
`•E.g. CFTR deltaF508 is incorrectly converted from
`protein change to DNA sequence in dbSNP
`Personalis solution:
`•Personalis’ QC process developing methods to
`accurately map published variants to the
`reference genome
`
`5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`13
`
`Personalis EX2083
`
`

`

`Personalis Genome Services: Annotation
` Personalis Proprietary DBs Provide Unique, Accurate, Comprehensive Content
`
`Varimed
`•
`Comprehensive, detailed, high quality curated Variant to phenotype DB
`•
`12,000+ papers manually curated, QC checked for quality
`•
`~500,000 variant to phenotype relationships
`•
`~200,000 variants described
`•
`~5000 phenotypes described
`•
`Large number of variants outside of exomes
`•
`Updated weekly with >200 new papers
`
`MendelDB
`•Personalis curated database of Mendelian phenotypes
`•Manually QC’d for quality
`•Most common 300+ Mendelian phenotypes represented and
`thousands of pathogenic variants
`
`PharmGKB
`•Worlds leading curated PGx database
`•Manually QC’d for quality
`•12 years, $30M NIH funding
`•Exclusive commercial license
`•376 drugs, >4000 variant annotations
`
`Regulome
`•
`Hundreds of thousands of putative transcription factor binding sites
`•
`Multiple levels of evidence, with ~40,000 in Tier 1
`•
`Enables annotation outside of exome
`
`High Quality, Reliable,
`Comprehensive
`Genome scale Variant
`to Disease Annotations
`
`High Quality Variant to
`Drug Phenotype
`Annotations
`
`Enables Interpretation
`of Intergenic regions
`outside of Exomes
`
`Proprietary content
`powers Personalis
`Analytics enabling novel
`biomedical insights
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`14
`
`Personalis EX2083
`
`

`

`Personalis Genome Services: Annotation
`Personalis Public DB Annotation Engine is Comprehensive and Current
`
`•
`
`•
`
`•
`
`Complement to our high
`quality proprietary databases
`
`> 30 public databases
`integrated in to our variant
`annotation output, useful as
`filtering criteria. This is
`significantly more than our
`competitors
`
`Cross referencing with our
`proprietary databases reveal
`significant errors in public
`DB’s such as dbSNP, OMIM,
`etc
`
`• Maintained, integrated, and
`updated as new versions are
`released
`
`•
`
`General framework for
`integrating new databases as
`they appear
`
`Gene Annotations
`Region Annotations
`
`Population Frequencies
`
`Mutational Impact
`
`Conservation
`Known Variants
`Structural Variations
`Variant to Disease
`Relationships
`Networks, Interactions,
`Pathways
`
`RefSeq, Entrez, AILUN, Ensembl, UCSC KnownGene
`Cytoband, TFBS, miRNAs, TargetScan (miRNA
`Targets), Segmental Duplications
`1000 Genomes, ESP 5400 Exomes, CG Genome
`Diversity Panel, HapMap
`dbNSFP, SIFT, Polyphen2,PhyloP, GERP++, Mutation
`Taster
`PhastCons, Evofold
`dbSNP 130,131,132,135
`DGV
`OMIM, ClinVar, Genetic Associations Database
`(GAD), GWAS Catalog, HGMD
`Reactome, HPRD, BioCyc, WikiPathways, KEGG, PID
`
`Functional Annotations
`
`GeneOntology
`
`Drug Targets
`Genetic Tests
`
`DrugBank
`Genetic Testing Registry
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`15
`
`Personalis EX2083
`
`

`

`Personalis Genome Services: Analytics
` Leading-edge Analytics for Case-Control and Familial Studies
`
`•
`
`Leading-edge analytical methods focused on Case Control Studies where
`typically scientist are analyzing 10’s to 1000’s of genomes
`– Disease Case-Control, Population, Patient Stratification, and PGx Studies
`– Exome >> Whole Genome
`• Critical for helping scientists distill sequence data into actionable science
`• Personalis analytics calculate statistically significant differences between
`cases and controls for:
`– Variants, Genes, GeneSets, Pathways, PharmGKB pathways, Varimed Disease Risk
`– Each enrichment is calculated assuming a recessive, dominant or additive risk model
`– The result is 15 different reports
`– Computationally intensive, requires >80 million Fisher’s exact tests
`– Use of Madsen-Browning collapsing method which is best of breed
`• Analytics utilize proprietary databases comprehensiveness and depth to
`provide differentiated analysis results for disease and PGx associations
`For Version 1, we will be developing new analytics modules for enabling
`analysis of family trios and larger pedigrees
`
`•
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`16
`
`Personalis EX2083
`
`

`

`Personalis Genome Services: Analytics
`Comprehensive and Actionable QC Reports
`
`• Detailed QC metrics are generated for all aspects of the Sequence
`Workflow including detailed reports for
`– Reads statistics
`– Alignment statistics
`– Variant calling statistics
`• Proprietary QC metrics and flagging of error regions not caught by
`conventional methods
`• At-A-Glance view allows rapid identification of problems and comparison
`between large numbers of samples
`• QC metrics include Personalis recommended “typical ranges” that enable
`flagging and interpretation of aberrant results for non-expert customers
`• Metrics are accompanied by explanations for actionability
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`17
`
`Personalis EX2083
`
`

`

`Personalis Genome Services
`Key Deliverables to the Customer
`
`Sequencing
`
`Pipeline
`
`Annotation
`
`Analytics
`
`Sample Prep
`
`Sequencing
`
`Alignment
`
`Variant
`Discovery
`
`Proprietary DB
`Annotation
`
`Public DB
`Annotation
`
`QC Reports
`
`Analysis &
`Interpretation
`
`Raw Reads
`(x N)
`Laboratory QC Statistics
`(HTML x N)
`
`Alignment Files
` (BAM Files x N)
`
`General Variant Report
`w/ Public DB Anno (Excel)
`
`Variant Calls for SNPs, small Indels
`(multisample VCF file)
`
`Variant Calls for SVs and CNVs
`(.GFF file x N)
`
`Rare Functional Variants Report
`w/ Proprietary DB Anno (Excel)
`
`Enriched Variants Report x 3 RM
`w/ Proprietary DB Anno (Excel)
`
`Enriched Genes Report x 3 RM
`w/ Proprietary DB Anno (Excel)
`
`Enriched Pathways Report x 3 RM
`w/ Proprietary DB Anno (Excel)
`
`Enriched Disease Report x 3 RM
`(w/ Proprietary DB Anno (Excel)
`
`Reads QC Statistics
`(HTMLx N)
`
`Alignment QC Statistics
`(HTML x N)
`
`Variant QC Statistics
`(HTML x N)
`
`At-A-Glance Report
`(HTML x N)
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`18
`
`Personalis EX2083
`
`

`

`Personalis Genome Services
`Competitive Analysis of Key Features
`
`Platform
`
`Platforms supported
`
`Results delivery format
`
`Personalis
`PGS (Version
`1)
`
`PGS (Prototype)
`
`Informatics Companies
`
`Genome Center
`
`Knome
`
`DNANexus
`
`Omicia
`
`Ingenuity
`
`BGI
`
`Platform Companies
`Complete
`Genomics
`
`Illumina
`
`Illumina
`
`Illumina,, CG
`
`Illumina
`
`Illumina,
`CG,ABI
`
`Illumina
`
`Illumina, CG
`
`Illumina
`
`CG
`
`Illumina
`
`Reports, Excel,
`Datafiles
`
`Reports, Excel,
`Datafiles
`
`Report, DB,
`Datafiles
`
`Web
`Portal/Cloud
`
`Reports,
`Datafiles
`
`Web Portal
`
`Reports, Excel,
`Datafiles,Cloud
`
`Reports, Excel,
`Datafiles,
`Cloud
`
`Reports, Excel,
`Datafiles,Cloud
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
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`
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`
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`
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`
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`
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`
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`
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`
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`
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`
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`
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`
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`
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`
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`
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`
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`
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`
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`
`
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`
`
`
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`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Sequencing
`Exome
`Exome Plus
`WGS Plus
`CLIA
`Pipeline
`Mapping
`Enhanced Public Reference
`SNP/Short Indel Detection
`SV Detection
`Zygosity, breakpoints for SV’s
`Phasing
`MEI’s
`Annotations/Content
`Public DB Anno
`Proprietary DB: Variants to Dz
`Proprietary DB: Variants to Drug
`Proprietary DB: Variants to Mend Dz
`Proprietary DB: Variants to TFBS
`Proprietary DB: Pathways/Networks
`Analytics
`Case-Control Analytics
`Family Pedigree Analytics
`QC Analytics/Reports
`Normal Range Reporting
`Propagation of Error/Quality
`Exploration Capability
`Public Genome Visual/Explor Tools
`Proprietary Visual/Explor Tools
`Publication Ready Graphics
`
`9/5/12
`
`
`
`
`
`
`
`
`
`
`
`
`
`
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`
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`
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`
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`
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`
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`
`
`
`
`
`
`
`
`
`
`
`Personalis, Inc. Proprietary and Confidential
`
`
`
`
`
`
`
`
`
`
`
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`
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`
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`
`
`
`
`
`
`
`
`19
`
`
`
`30+
`
`
`
`
`
`
`
`
`
`
`
`
`
`30+
`
`
`
`
`
`
`
`
`
`
`
`
`
`10+
`
`
`
`
`
`
`
`
`
`
`
`
`
`<5
`
`
`
`
`
`
`
`
`
`
`
`
`
`10+
`
`
`
`
`
`
`
`
`
`
`
`
`
`20+
`
`
`
`
`
`
`
`
`
`
`
`
`
`<5
`
`
`
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`
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`
`<5
`
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`
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`
`
`
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`
`<5
`
`
`
`
`
`
`
`
`
`
`
`
`
`Personalis EX2083
`
`

`

`Personalis Genome Services
`Competitive Analysis of Key Features
`
`Personalis
`PGS (Version
`1)
`
`PGS (Prototype)
`
`Informatics Companies
`
`Genome Center
`
`Knome
`
`DNANexus
`
`Omicia
`
`Ingenuity
`
`BGI
`
`Platform Companies
`Complete
`Genomics
`
`Illumina
`
`Illumina
`
`Illumina,, CG
`
`Illumina
`
`Illumina,
`CG,ABI
`
`Illumina
`
`Illumina, CG
`
`Illumina
`
`CG
`
`Illumina
`
`Platform
`
`Platforms supported
`
`Results delivery format
`
`Reports, Excel,
`Datafiles
`
`Reports, Excel,
`Datafiles
`
`Report, DB,
`Datafiles
`
`Web
`Portal/Cloud
`
`Reports,
`Datafiles
`
`Web Portal
`
`Reports, Excel,
`Datafiles,Cloud
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`No Sequencing Option
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Reports, Excel,
`Datafiles,Cloud
`
`Reports, Excel,
`Datafiles,
`Cloud
`No Exomes
`
`
`
`
`
`
`
`
`
`
`
`
`
`
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`
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`
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`
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`
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`
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`
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`
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`
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`
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`
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`
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`
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`
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`
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`
`
`
`
`
`
`
`
`
`
`
`
`
`Limited Pipeline
`
`
`
`
`
`
`
`
`
`
`
`
`
`
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`
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`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Sequencing
`Exome
`Exome Plus
`WGS Plus
`CLIA
`Pipeline
`Mapping
`Enhanced Public Reference
`SNP/Short Indel Detection
`SV Detection
`Zygosity, breakpoints for SV’s
`Phasing
`MEI’s
`Annotations/Content
`Public DB Anno
`Proprietary DB: Variants to Dz
`Proprietary DB: Variants to Drug
`Proprietary DB: Variants to Mend Dz
`Proprietary DB: Variants to TFBS
`Proprietary DB: Pathways/Networks
`Analytics
`Case-Control Analytics
`Family Pedigree Analytics
`QC Analytics/Reports
`Normal Range Reporting
`Propagation of Error/Quality
`Exploration Capability
`Public Genome Visual/Explor Tools
`Proprietary Visual/Explor Tools
`Publication Ready Graphics
`
`9/5/12
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Analytics Limited By Content
`
`
`
`Limited Analytics
`
`
`
`
`
`
`
`
`
`
`
`
`
`
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`
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`
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`
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`
`
`
`
`
`
`
`
`
`
`
`
`
`Personalis, Inc. Proprietary and Confidential
`
`
`
`
`
`
`
`
`
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`
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`
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`
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`
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`
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`
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`
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`
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`
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`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`20
`
`
`
`30+
`
`
`
`
`
`
`
`
`
`
`
`
`
`30+
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`10+
`<5
`10+
`
`
`
`Lack of Proprietary Content
`
`
`
`
`
`
`
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`
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`
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`
`
`
`
`
`
`
`
`
`
`
`
`
`
`20+
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Lack of Proprietary and
`<5
`<5
`<5
`
`
`Limited Public Content
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Personalis EX2083
`
`

`

`Personalis Genome Services
`Personalis IP
`
`Personalis
`PGS (Version
`1)
`
`PGS (Prototype)
`
`Informatics Companies
`
`Genome Center
`
`Knome
`
`DNANexus
`
`Omicia
`
`Ingenuity
`
`BGI
`
`Platform Companies
`Complete
`Genomics
`
`Illumina
`
`Illumina
`
`Illumina,, CG
`
`Illumina
`
`Illumina,
`CG,ABI
`
`Illumina
`
`Illumina, CG
`
`Illumina
`
`CG
`
`Illumina
`
`Platform
`
`Platforms supported
`
`Results delivery format
`
`Reports, Excel,
`Datafiles
`
`Reports, Excel,
`Datafiles
`
`Report, DB,
`Datafiles
`
`Web
`Portal/Cloud
`
`Reports,
`Datafiles
`
`Web Portal
`
`Reports, Excel,
`Datafiles,Cloud
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`No Sequencing Option
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Reports, Excel,
`Datafiles,Cloud
`
`Reports, Excel,
`Datafiles,
`Cloud
`No Exomes
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Limited Pipeline
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Sequencing
`Exome
`Exome Plus
`WGS Plus
`CLIA
`Pipeline
`Mapping
`Enhanced Public Reference
`SNP/Short Indel Detection
`SV Detection
`Zygosity, breakpoints for SV’s
`Phasing
`MEI’s
`Annotations/Content
`Public DB Anno
`Personalis IP
`Proprietary DB: Variants to Dz
`Proprietary DB: Variants to Drug
`Proprietary DB: Variants to Mend Dz
`Proprietary DB: Variants to TFBS
`Proprietary DB: Pathways/Networks
`Analytics
`Case-Control Analytics
`Family Pedigree Analytics
`QC Analytics/Reports
`Normal Range Reporting
`Propagation of Error/Quality
`Exploration Capability
`Public Genome Visual/Explor Tools
`Proprietary Visual/Explor Tools
`Publication Ready Graphics
`
`9/5/12
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Analytics Limited By Content
`
`
`
`Limited Analytics
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Personalis, Inc. Proprietary and Confidential
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`21
`
`
`
`30+
`
`
`
`
`
`
`
`
`
`
`
`
`
`30+
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`10+
`<5
`10+
`
`
`
`Lack of Proprietary Content
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`20+
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Lack of Proprietary and
`<5
`<5
`<5
`
`
`Limited Public Content
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Personalis EX2083
`
`

`

`MendelDB Dashboard
`
`•
`
`•
`
`•
`
`High quality curated DB of Mendelian
`phenotypes and their variants
`– Managed by Sarah Garcia and Gemma
`Chandratillake, both Genetics Ph.D. & Genetic
`Counselors
`
`Critical content to support Disease Variant
`Discovery Service and Genome Interpretation
`Service
`
`On track to finish all (~560) GeneReviews by Oct
`2012, corresponding to >300 common
`Mendelian disease phenotypes
`
`• Will then continue phenotype curation and
`variant curation from other sources
`
`•
`
`Flexible workforce for other curation tasks in the
`future
`
`# phenotypes
`
`# genes (blue)
`# variants (red)
`
`productivity
`(rows/hr)
`
`Raw error rate
`(# errors/row)
`(prior to QC)
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`22
`
`Personalis EX2083
`
`

`

`VarimedDB Dashboard
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`23
`
`Personalis EX2083
`
`

`

`Scientific Computing Infrastructure
`
`• Genome processing capability increased from 80 to 350 cores
`• Added ~120TB usable storage for R&D (Hitachi) for a total of >300 TB of
`storage
`– Bidding war between NetApp, Hitachi, Isilon, Dell
`Increased speed of internal network to 10G
`Server backup planning in progress
`– Disk to Disk to Cloud + Tape for most critical data
`• Continuing search for Linus/Unix sys admin
`
`•
`•
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`24
`
`Personalis EX2083
`
`

`

`Scientific Computing Infrastructure
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`25
`
`Personalis EX2083
`
`

`

`Summary of Estimated Timelines
`
`Mar
`
`Apr
`
`May
`
`Jun
`
`Jul
`
`Aug
`
`Sept
`
`Oct
`
`Nov
`
`Dec
`
`Jan
`
`Feb
`
`Personalis Genome
`Services
`
`Spec & Resource
`
`Prototype Development
`
`Disease Variant
`Discovery Service
`
`Feasibility Assess
`
`Prototype Testing w/ Customer
`
`v1 Development
`
`v1 Testing
`
`v1 Launch
`
`Spec & Resource
`
`Prototype Development
`
`Genome
`Interpretation Service
`
`Feasibility Assess
`
`Spec & Resource
`
`Prototype Testing w/ Collaborator
`
`v1 Dev
`
`Prototype Development
`
`Prototype Testing
`w/ Collaborator
`
`Now Revising Timelines & Reprioritizing accounting for:
`•
`New /Exome Plus initiative (Required for V1 Release?)
`•
`Demands of Moyamoya project and other early customers
`•
`DVDS and GIS
`•
`Hiring Delays
`•
`Early Feedback on Prototype
`Personalis, Inc. Proprietary and Confidential
`
`26
`
`9/5/12
`
`Personalis EX2083
`
`

`

`•
`
`•
`
`•
`
`R&D Hiring Update
`
`New Hires
`•
`Anil Patwardhan, Ph.D.: Senior Bioinformatics Scientist joining BI Apps & Research Team (Starting Sept 17th)
`
`Slower hiring ramp than plan: ~ 2 months behind on Bioinformatics, Scientific computing hires
`•
`Low volume of resumes through recruiters – has improved in past 2-3 weeks, starting to see steady flow of candidates, expanding
`number of recruiters involved
`Looking for great hires, being very selective
`Bioinformaticians and Unix Sys Admins are in high demand
`
`•
`•
`
`Near Term Open Positions
`•
`Linux systems admin – hired new recruiter, looking for consulting help
`•
`Test/Build Engineer
`•
`BI Applications Engineer
`•
`BI Pipeline Engineer
`•
`BI Statistician
`
`R&D
`
`Pipeline
`Mgr
`(Lam)
`
`BI Pipeline
`Engineer
`(Newburge
`r)
`
`BI Pipeline
`Engineer
`
`Build/Test
`Engineer)
`
`BI Analyst
`(Bartha)
`
`Director
`Accuracy
`R&D
`(Pratt)
`
`BI Tools
`(Harris)
`
`BI Apps &
`Research
`Mgr
`(Chen)
`
`BI App
`Engineer
`
`Mol
`Bio/Lab
`(Luo)
`
`BI App
`Scientist
`(Clark)
`
`Scientific
`Content &
`Curation
`Mgr
`
`Sr Project
`Mgr
`(Kirk)
`
`Linux
`Systems
`Admin
`
`BI Scientist
`(Patwardha
`n)
`
`Genomics
`Counselor
`(Chandratill
`ake)
`
`Genomics
`Counselor
`(Garcia)
`
`5 Part Time
`Curation
`Scientists
`
`Original Team
`
`New hires (started)
`
`New hires (not yet started)
`
`Near Term Open Positions
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`27
`
`Personalis EX2083
`
`

`

`Summary of Resource Allocation
`
`Accuracy R&D
`Mark Pratt
`Gabor Barth
`Jason Harris
`Shujun Luo
`
`Pipeline R&D
`Hugo Lam
`Daniel Newburger
`
`Apps R&D
`Rong Chen
`Michael Clark
`
`Content R&D
`Sarah Garcia
`Gemma Chandratillake
`PT Curators
`
`Personalis
`Genome
`Services
`Disease Variant
`Discovery
`Service
`Genome
`Interpretation
`Service
`
`Research
`Collaborations
`Ethics Board
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`28
`
`Personalis EX2083
`
`

`

`Overall R&D Risks and Mitigation
`
`Risk
`• R&D hiring delay of BI engineers and Unix sys admin.
`May impact schedule
`
`• Long lead time content curation and content quality
`items for GIS and DVDS
`• Licensing of applications and content for analysis
`
`• Ethical use of Genomes for R&D
`
`• Product Differentiation
`
`• Identifying high quality collaborators for testing our
`services. Potentially long lead time.
`
`Mitigation
`• New IT recruiters now involved for Unix sys admin
`hire
`• Redoubled efforts on BI hires (new process,
`conferences, networking)
`• Started dev on those items with long lead times to
`develop concurrently with Pipeline (MendelDB, etc)
`• Systematically reviewing and applying for licenses
`for key content and algorithms
`• Ethics board approval for all Genomes used for R&D
`• Part of orientation training
`• Continuing to push differentiation in three key
`areas: Accuracy/Quality, Content, Features
`• Have identified and started working with customers
`to test Prototype
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`29
`
`Personalis EX2083
`
`

`

`Next Steps & Priorities
`
`•
`
`•
`
`•
`
`•
`
`•
`
`Start planning, resourcing, prioritization, and development process for Version 1.
`Will need to accommodate R&D resources required for:
`– Laboratory development (Exome Plus)
`– Collaboration/Customer projects
`– Hiring/Interviewing
`– Feedback from Prototype
`
`Continue Hiring for open positions
`
`Continue to Identify customers for testing Pipeline Service Prototype
`
`Continue to execute on content priorities, develop longer term content strategy
`
`Continue to execute on Accuracy objectives and integration with laboratory
`capabilities
`
`9/5/12
`
`Personalis, Inc. Proprietary and Confidential
`
`30
`
`Personalis EX2083
`
`