Personal health citzenship

Huntington's Chorea Nancy Wexler’s family

AdrenoleukodystrophyAugusto Odone’s son

Doug Melton’s son, Sam, has diabetes

Parkison’s DiseaseMichael J. Fox

Cancer, substance

abuseBetty Ford

Hugh Rienhoff

PersonalGenome.org

PersonalGenome.org Project Goals

1) Active subject participation, informed redactions2) Entrance exam to ensure highly informed consent3) Subject & public access (not just research elite) 4) Eliminate over-promising de-identification 5) Scaleable to millions of research subjects, via inexpensive DNA/trait data, donations6) Highly integrated, holistic, systems-biology

7) Subjects informed enough to “opt-out”8) Life-impacting info can reach subjects9) Cells available for personal functional genomics

Reducing costs via open-sourcehardware, software, wetware, ELSware

Factor • 30 Equipment speed: from 1 up to 30 Mpixels/sec camera• 4 Equipment cost: from $500K down to $124K (Danaher Inc)• 36 Parallelism: 36 flow-cells per camera, 60M beads each

• 15 Flow cell volume: 1.5 mm down to 0.01 or 0.02 mm• 40 Kit costs: $2000 down to $50 at standard enzyme costs• 10 Enzymes: $4000/mg down to <$400 (Enzymatics Inc)• 50 Genomic subset enrichment (Exome – 1% genome)

Error rate: 3E-7 at >=3X coverage

PersonalGenome.org

G

A

C

T

Multiplex Cyclic Sequencing by Synthesis (Next-gen, polonies on slides or beads)

Polymerase -or- LigaseShendure,

Porreca, et al. 2005 Science

Illumina, IBS

AB-SOLiD, CGI

Mitra, et al. 2003 Analyt.

Biochem.1999NAR

PersonalGenome.org

G.007 Hardware open-CAD

• 30 msec move/settle• 42 kbp/sec• 10-60 Gbp/run• $124,000

EM-CCD Camera

Xenon Light

Fluidics

Autofocus

Objective

Stage

3U Imaging2U Sequencing

G.007-HardwareNikon, Hamamatsu, Alcott, Prior, Sutter, Bioptechs, PI, Uniblitz, Superlogics

Shendure, Porreca et al. 2005

Danaher, Hamamatsu, Nikon$124K with computer & 1 yr serviceContact:kevin.mccarthy@danahermotion.com

Rich Terry et al. 2007

DIY

PersonalGenome.org

36 Flowcells G007

PersonalGenome.org

Gel array, 12M beadsShendure, Porreca et al. 2005

Glass array, 60M beadsKim, Porreca et al. 2007

1.6M reads 12M reads(M. Umbarger)

Higher density & accuracy

PGP & G.0072005 2007 2008

Bases per run 30 Mbp 11 Gbp 30 Gbp

Bases per read 26 26 36

Cost per megabase $80 $2.88 $0.50

Cost per 1% diploid (20x 30Mbp)

$37,000 $1,800 $300

Reagent Volume Street price Bulk

T4 ligase 10 ml $26,000 $1,700

Hot-start Taq 50 ml $60,700 $2,000

Nonamers 40 ml $41,500 $1,600

Nucleotides 120 ml $29,000 $3,500

Beads 54 ml $6,000 $1,000?

Monthly reagent usagePersonalGenome.org