Personal health citzenship Huntington's Chorea Nancy Wexler’s family Adrenoleukodystrophy Augusto Odone’s son Doug Melton’s son, Sam, has diabetes Parkison’s Disease Michael J. Fox Cancer, substance abuse Betty Ford Hugh Rienhoff PersonalGenome.org

PersonalGenome.org Project Goals 1) Active subject participation, informed redactions 2) Entrance exam to ensure highly informed consent 3) 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, donations 6) Highly integrated, holistic, systems-biology 7) Subjects informed enough to “opt-out” 8) Life-impacting info can reach subjects 9) Cells available for personal functional genomics

Reducing costs via open-source hardware, 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- Ligase Shendure, Porreca, et al Science Illumina, IBS AB- SOLiD, CGI Mitra, et al Analyt. Biochem NAR PersonalGenome.org

G.007 Hardware open-CAD 30 msec move/settle 42 kbp/sec Gbp/run $124,000 EM-CCD Camera Xenon Light Fluidics Autofocus Objective Stage 3U Imaging 2U Sequencing

G.007-Hardware Nikon, Hamamatsu, Alcott, Prior, Sutter, Bioptechs, PI, Uniblitz, Superlogics Shendure, Porreca et al Danaher, Hamamatsu, Nikon $124K with computer & 1 yr service Contact: Rich Terry et al DIY PersonalGenome.org

36 Flowcells G007 PersonalGenome.org

Gel array, 12M beads Shendure, Porreca et al Glass array, 60M beads Kim, Porreca et al M reads 12M reads (M. Umbarger) Higher density & accuracy

PGP & G Bases per run30 Mbp11 Gbp30 Gbp Bases per read26 36 Cost per megabase$80$2.88$0.50 Cost per 1% diploid (20x 30Mbp) $37,000$1,800$300 ReagentVolumeStreet price Bulk T4 ligase10 ml$26,000 $1,700 Hot-start Taq50 ml$60,700 $2,000 Nonamers40 ml$41,500 $1,600 Nucleotides120 ml$29,000 $3,500 Beads54 ml $6,000 $1,000? Monthly reagent usage PersonalGenome.org