DNSSEC: Where We Are (and how we get to where we want to be)
Where are we now? Where do we want to go?
22
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?
description
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:. Human Systems Biology. Integrate diverse data types -- holistic not just inherited genome sequence - PowerPoint PPT Presentation
Transcript of Where are we now? Where do we want to go?
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
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
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
4
DNA Explorer, $80 (Ages 10 and up) www.discovery.com
Genographic Project $99
DIY DNA
23andme $399Time Magazine Nov 2008 invention of the year
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 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
7
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)
8
Imaging Diagnostics
Control
22q11DS
Noonan
Smith-Magenis
William’s
Hammond et al, Am J Med Genet 2004, Am J Hum Genet 2005
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
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
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
12
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
10
1990 1995 2000 2005 2010
$/bp
13
$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
14
Over 600 alleles of BRCA1 (Myriad/DNAdirect* sequencing not chips)
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’sMichael J. Fox
Cancer, substance
abuseBetty Ford
Hugh RienhoffMyDaughtersDNA.org
ALS Heywood familyPatientsLikeMe.com
(non-anonymous action in response to “non-actionable” tests)
16
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.
17
PGP MicrobiomeResistome: 18 Antibiotics
Dantas, Sommer, Churchunpublished
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
VH*DH*NNHH*JJHH*V*JJ
46*23*N N * 6 6 * 67* 55 = > 2M combinations , 750 bp, >1E10 cells
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
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
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)
22
.
