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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?

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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)

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PersonalGenomes.orgInherited + Environmental Genomics

VDJ-ome

TRAITS(Phenome)

Personal stem-cellsepigenome (RNA,mC)

PERSONAL GENOME3M alleles

One in a life-time genome + yearly ( to daily) tests

Public Health Bio-weather map : Allergens, Microbes, Viruses

Microbiome

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DNA Explorer, $80 (Ages 10 and up) www.discovery.com

Genographic Project $99

DIY DNA

23andme $399Time Magazine Nov 2008 invention of the year

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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?

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6 of the first 8 full diploid genomes are non-anonymous

1. JCV Celera/JCVI2. JDW Roche/Baylor3. MK LUMC4. DS Knome5. RP Knome6. YH BGI

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Trends toward opennessHR 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)

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Imaging Diagnostics

Control

22q11DS

Noonan

Smith-Magenis

William’s

Hammond et al, Am J Med Genet 2004, Am J Hum Genet 2005

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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

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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

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Intelligent Bio-SystemsSystems

SAB & PGP SAB SAB

8 Next Generation Sequencing Platforms

Roche Illumina AB-SOLiD Helicos Polonator

$500K $680K $690K $1350K $155K

.001G/0.03h 0.2 G /2.6h 0.3 G /4h 2.8 G/2h 2G/2h

VDJ-grant Exomes Co-develop SAB Co-develop

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Sequencing tracked Moore’s law (2X / 2 yr) until 2004-8 (10X / yr)

40X 98% genome $5K in Q2-2009 ($50 for 1%?)

0.0000001

0.000001

0.00001

0.0001

0.001

0.01

0.1

1

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1990 1995 2000 2005 2010

$/bp

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$1

$10

$100

$1,000

$10,000

$100,000

$1,000,000

1E+1 1E+3 1E+5 1E+7 1E+9 1E+11

Basepairs

Genographic

DNAdirect

Navigenics $2500

23andme $400

PersonalGenome.org

KnomeCGI

98%

Plummeting costs & diversity of options

0.02%

1%

sequencing

sequencing

chips

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

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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’sMichael J. Fox

Cancer, substance

abuseBetty Ford

Hugh RienhoffMyDaughtersDNA.org

ALS Heywood familyPatientsLikeMe.com

(non-anonymous action in response to “non-actionable” tests)

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PersonalGenomes.org : gene/environment/trait data

1) Avoid over-promising on de-identification 2) 100% on Exam to assure informed consent3) 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 genomics7) 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.

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PGP MicrobiomeResistome: 18 Antibiotics

Dantas, Sommer, Churchunpublished

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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

VH*DH*NNHH*JJHH*V*JJ

46*23*N N * 6 6 * 67* 55 = > 2M combinations , 750 bp, >1E10 cells

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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)

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PersonalGenomes.orgInherited + Environmental Genomics

VDJ-ome

TRAITS(Phenome)

Personal stem-cellsepigenome (RNA,mC)

PERSONAL GENOME3M alleles

One in a life-time genome + yearly ( to daily) tests

Public Health Bio-weather map : Allergens, Microbes, Viruses

Microbiome

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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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