1. 1 9:05-9:25 AM 17-Nov-2008 NAS: Collecting, storing, protecting & accessing biological data collected in social surveys Thanks to: Where are we now? Where do we want to go?

2. 2 Human Systems Biology One TRAIT per cohort Deidentified GENOME Integrate diverse data types -- holistic not just inherited genome sequence Limited traits (dual use technologies: research & clinical)

3. 3 PersonalGenomes.org Inherited + Environmental Genomics VDJ-ome TRAITS (Phenome) Personal stem-cells epigenome (RNA,mC) PERSONAL GENOME 3M alleles One in a life-time genome + yearly ( to daily) tests Public Health Bio-weather map : Allergens, Microbes, Viruses Microbiome

4. 4 DNA Explorer, $80 (Ages 10 and up) www.discovery.com Genographic Project $99 DIY DNA 23andme $399 Time Magazine Nov 2008 invention of the year

5. 5 Genetic Exceptionalism? Standard of care (non-genetic): Sedentary? Statins? Vegan? Aspirin? Wine? Cell-phones? Cars? Very small odds-ratios, aimed at public health rather than individuals Conventional clinical genetics: PKU, BRCA1.. 1361 genes (+5/week) > 4M babies/yr in USA Highly predictable & huge impact. Why shouldn’t genetics deal with small (uncertain) risk factors like the rest of medicine?

6. 6 6 of the first 8 full diploid genomes are non-anonymous 1.JCVCelera/JCVI 2.JDWRoche/Baylor 3.MKLUMC 4.DSKnome 5.RPKnome 6.YHBGI

7. 7 Trends toward openness HR 2764 “SEC. 218. all investigators funded by the NIH submit.. an electronic version of their final, peer-reviewed manuscripts.., to be made publicly available” (make science paid for by tax-payers accessible to the tax-payers, not just the experts) PatientsLikeMe.com: MS, Parkinson’s, ALS, Depression, Anxiety, Bipolar, OCD, HIV/AIDS “sharing your healthcare experiences and outcomes is good.” (Full names & photos)

8. 8 Imaging Diagnostics Control 22q11DS Noonan Smith-Magenis William’s Hammond et al, Am J Med Genet 2004, Am J Hum Genet 2005

9. 9 Is promising anonymity realistic? Are we in denial? Trends in laws to make data public (not just at elite institutions): e.g. H.R. 2764, SEC. 218. 26Dec07 open-access for all NIH-funded research. SEC, GINA, etc (12) Identify individual case/control status from pooled SNP data Homer et al PLoS Genetics 2008 (11) Re-identification after “de-identification” using public data. Group Insurance list of birth date, gender, zip code sufficient to re-identify medical records of Governor Weld & family via voter-registration records (1998) Self identification trend (genome-altruists) (10) Unapproved self-identification. e.g. Celera IRB. (Kennedy Science. 2002) (9) Obtaining data about oneself via FOIA or sympathetic researchers. (8) DNA data CODIS data in the public domain. even if acquitted index

10. 10 Is promising anonymity realistic? Are we in denial? Accessing “Secure data” (7) Laptop loss. 26 million Veterans' medical records, SSN & disabilities stolen Jun 2006. (6) Hacking. A hacker gained access to confidential medical info at the U. Washington Medical Center -- 4000 files (names, conditions, etc, 2000) (5) Combination of surnames from genotype with geographical info An anonymous sperm donor traced on the internet 2005 by his 15 year old son who used his own Y chromosome data. (4) Identification by phenotype. If CT or MR imaging data is part of a study, one could reconstruct a person’s appearance. Even blood chemistry can be identifying in some cases. (3) Inferring phenotype from genotype Markers for eye, skin, and hair color, height, weight, geographical features, dysmorphologies, etc. are known & the list is growing. (2) “Abandoned DNA bearing samples (e.g. hair, dandruff, hand-prints, etc.) (1) Government subpoena. False positive IDs and/or family coercion index

11. 11 Intelligent Systems Bio-Systems SAB & PGPSAB 8 Next Generation Sequencing Platforms RocheIlluminaAB-SOLiDHelicosPolonator $500K$680K$690K$1350K$155K.001G/0.03h0.2 G /2.6h0.3 G /4h2.8 G/2h2G/2h VDJ-grantExomesCo-developSABCo-develop

12. 12 Sequencing tracked Moore’s law (2X / 2 yr) until 2004-8 (10X / yr) 40X 98% genome $5K in Q2-2009 ($50 for 1%?) $/bp

13. 13 Genographic DNAdirect Navigenics $2500 23andme $400 PersonalGenome.org Knome CGI 98% Plummeting costs & diversity of options 0.02% 1% sequencing chips

14. 14 Over 600 alleles of BRCA1 (Myriad/DNAdirect* sequencing not chips)

15. 15 What if there is no current cure? Huntington's Chorea Nancy Wexler’s family Adrenoleukodystrophy Augusto Odone’s son Doug Melton’s son, Sam, has diabetes Parkinson’s Michael J. Fox Cancer, substance abuse Betty Ford Hugh Rienhoff MyDaughtersDNA.org ALS Heywood family PatientsLikeMe.com (non-anonymous action in response to “non-actionable” tests)

16. 16 PersonalGenomes.org : gene/environment/trait data 1) Avoid over-promising on de-identification 2) 100% on Exam to assure informed consent 3) Open access (very low barrier to researchers) 4) Low cost coding sequence + regulatory data 5) Multi-traits: imaging, iPS stem cell RNA, microbes 6) Cells available for personal functional genomics 7) IRB approval for 100,000 diverse volunteers 0431 1070 1660 1677 1687 1833 1846 1731 1730 1781 Lunshof JE, Chadwick R, Vorhaus DB, Church GM. From genetic privacy to open consent. Nat Rev Genet. 2008 Lunshof JE, Chadwick R, Church GM (2008) Hippocrates revisited? Old ideals and new realities. Genomic Med. 2(1-2):1-3.

17. 17 PGP Microbiome  Resistome: 18 Antibiotics Dantas, Sommer, Church unpublished

18. 18 Antibody ( & TCR) VDJ regions Roth DB et al Mol Cell Biol. 1989 9:3049 N (1-13): 14 22 13 15 10 4 5 4 2 2 3 2 1 Lefranc, The Immunoglobulin FactsBook; Janeway, Immunobiology 2001 N H J H J  V H *D H *N H *J H *V  *J  N 6 5 46*23*N * 6 * 67* 5 = > 2M combinations, 750 bp, >1E10 cells

19. 19 N-region lengths in circulating B-cells 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Length (aa)

20. 20 PersonalGenomes.org Inherited + Environmental Genomics VDJ-ome TRAITS (Phenome) Personal stem-cells epigenome (RNA,mC) PERSONAL GENOME 3M alleles One in a life-time genome + yearly ( to daily) tests Public Health Bio-weather map : Allergens, Microbes, Viruses Microbiome

21. 21 Personal Genomics Scope (& Issues) Ancestry (paternity) Forensics (abandoned DNA) Research (anonymity issues) Science education/curiosity (more) Microbes, immune, RNA, cancer (more research) Investment preview (early adopters: cf. fax, PC, www) Medically actionable given new research or personal data Medically actionable immediately (setting data thresholds) (1361 clinical diseases in genetests.org 16-Nov-2008)

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