Transcript PersonalGenomes.org

Where are we now? Where do we want to go?
9:05-9:25 AM 17-Nov-2008 NAS: Collecting, storing, protecting &
accessing biological data collected in social surveys
Thanks to:
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Human Systems Biology
Integrate diverse data types -- holistic
not just inherited genome sequence
Limited traits
(dual use technologies: research & clinical)
Deidentified
GENOME
One TRAIT
per cohort
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PersonalGenomes.org
Inherited + Environmental Genomics
One in a life-time genome + yearly ( to daily) tests
Public Health Bio-weather map : Allergens, Microbes, Viruses
PERSONAL
GENOME
3M alleles
Personal
stem-cells
epigenome
(RNA,mC)
VDJ-ome
TRAITS
(Phenome)
Microbiome
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DIY DNA
DNA Explorer, $80
(Ages 10 and up)
www.discovery.com
Genographic Project $99
23andme $399
Time Magazine Nov 2008
invention of the year 4
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
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6.
JCV
JDW
MK
DS
RP
YH
Celera/JCVI
Roche/Baylor
LUMC
Knome
Knome
BGI
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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)
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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
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index
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
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index
8 Next Generation Sequencing Platforms
Roche
Illumina
AB-SOLiD Helicos
Polonator
$500K
$680K
.001G/0.03h 0.2 G /2.6h
$690K
0.3 G /4h
$155K
2G/2h
VDJ-grant
Co-develop SAB
Exomes
$1350K
2.8 G/2h
Co-develop
Intelligent
Bio-Systems
SAB & PGP
SAB
SAB
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Sequencing tracked Moore’s law
(2X / 2 yr) until 2004-8 (10X / yr)
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0.1
0.01
$/bp
0.001
0.0001
0.00001
0.000001
0.0000001
1990
1995
2000
2005
2010
40X 98% genome $5K in Q2-2009 ($50 for 1%?)
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Plummeting costs & diversity of options
Genographic
sequencing
DNAdirect
Navigenics $2500
23andme $400
1%
PersonalGenome.org
chips
0.02%
Knome
CGI
98%
sequencing
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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?
(non-anonymous action in response to “non-actionable” tests)
Doug
Melton’s
son, Sam,
has
Huntington's Chorea
diabetes
Nancy Wexler’s family
Adrenoleukodystrophy
Augusto Odone’s son
ALS
Heywood family
PatientsLikeMe.com
Parkinson’s
Michael J. Fox
Hugh Rienhoff
MyDaughtersDNA.org
Cancer,
substance
abuse
Betty Ford
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PersonalGenomes.org :
gene/environment/trait data
0431
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1) Avoid over-promising on de-identification
2) 100% on Exam to assure informed consent
3) Open access (very low barrier to researchers)
1070 1846
4) Low cost coding sequence + regulatory data
5) Multi-traits: imaging, iPS stem cell RNA, microbes
6) Cells available for personal functional genomics
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7) IRB approval for 100,000 diverse volunteers
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 Microbiome-Resistome: 18 Antibiotics
Dantas, Sommer, Church
unpublished
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Antibody (& TCR) VDJ regions
VH*DH*NH*JH*Vkl*Jkl
46*23*N * 6 * 67* 5 = > 2M combinations , 750 bp, >1E10 cells
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
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N-region lengths in circulating B-cells
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Length (aa)
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PersonalGenomes.org
Inherited + Environmental Genomics
One in a life-time genome + yearly ( to daily) tests
Public Health Bio-weather map : Allergens, Microbes, Viruses
PERSONAL
GENOME
3M alleles
Personal
stem-cells
epigenome
(RNA,mC)
VDJ-ome
TRAITS
(Phenome)
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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