scaling citizen science genomics
TRANSCRIPT
DIYgenomicsOpen-source preventive medicine and
scaling citizen science genomics
Melanie Swan Founder
DIYgenomics650-681-9482
@DIYgenomics www.DIYgenomics.org
July 28, 2011, OSCON, Portland OR
Slides: http://slideshare.net/LaBlogga
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About Melanie Swan
Founder DIYgenomics, hedge fund manager, futurist, entrepreneur
Current projects: MelanieSwan.com Work experience: Fidelity, JP Morgan, Arthur
Andersen, iPass, RHK/Ovum Education: MBA Finance, Wharton; BA
French/Economics, Georgetown Univ Sample publications
Swan, M. Multigenic Condition Risk Assessment in Direct-to-Consumer Genomic Services. Genet. Med. 2010, May;12(5):279-88.
Swan, M. Translational antiaging research. Rejuvenation Res. 2010, Feb;13(1):115-7.
Swan, M. Engineering Life into Technology: the Application of Complexity Theory to a Potential Phase Transition of Intelligence. Symmetry 2010, 2, 150:183.
Swan, M. Emerging patient-driven health care models: an examination of health social networks, consumer personalized medicine and quantified self-tracking. Int. J. Environ. Res. Public Health 2009, 2, 492-525.
Source: http://melanieswan.com/publications.htm
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Biology is an information technology
Image credit: http://pubs.acs.org/cen/_img/87/i50/8750cover2_law.gif
Image credit: http://www.nanoporetech.com/sequences
4th Gen: Electronic Sequencing
I hate you01001001001000000110100001100001011101000
110010100100000011110010110111101110101
I love you 01001001001000000110110001101111011101100110010100100000011110010110111101110101
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Biology is the information technology
Image credit: J. Craig Venter Institute
Image credit: Anthony Atala lab
Image credit: Thomas Matthiesen
Artificial cell booted to life
Algal biofuelImage credit: http://www.rexresearch.com
Whole organ decellularization and recellularization (heart)
Organ regeneration (urethra)
DNA nanotechnology latch box for drug delivery
Image credit: Aarhus University
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Agenda
Citizen science progress to date
Scaling citizen science
Grand vision next steps
Image credit: http://www.gettyimages.com
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Citizen science definition
Institutional science research
DIYbio
Citizen science: 200+ organizations1
1http://scienceforcitizens.net/finder
Investigation without professional training
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Politics of personalized genomics
U.S. Genetic Information Nondiscrimination Act (GINA) 2008
Our world is not Gattaca Genomic test regulation expected Genomic rights and petitions
Petition for Access to Genetic Information http://www.thepetitionsite.com/1/mydna
Petition for Health Data Rights http://www.healthdatarights.org
Health as a currency Health as a human right
Image credit: http://www.sonypictures.com
Image credit: http://sciencephoto.com
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Consumer genomics test landscape
Single/few condition Multiple condition Whole genome
Cost
1Lower cost with family group or medical condition Service Breadth
Public studies MatchmakingScientificMatch $1,995GenePartner $10-$99
PaternityGenelex $200-$475Identigene $149-$399
Pregnancy ScreeningCounsyl $349
NutrigenomicsAPO E Gene Diet $389Inherent Health $99
Coriell15 conditions
Scripps (Navigenics)28 conditions
Pers. Genome Proj.Conditions undisclosed
Harvard Med. Sch.
Genetic disorders,
PredispositionDNA Direct $200-$3,500Matrix Genomics $199-$799
Drug sensitivity,
$
Exome
23andme201 conditions
Navigenics*40 conditions
deCODEme49 conditions
$1,000
$99$299
Genomics71 conditions
Pathway*
$2,500
$999 $2,000
$985 *Must be physician-ordered
Knome
EdgeBio$6,000
$19,500
Knome
Illumina$48,000
$350,000
$99,500
$68,500
$5,0001
$39,500
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Genomics comparison scorecard
Consumer genomic service
# Cond-itions
Cost Report Data access
Visible research quality1
Updates
deCODEme 49 $2,000 + + 23andme 201 $99 +Navigenics* 40 $999 Pathway Genomics* 71 $299 Coriell (10,000
partic. 7/11)15 public
study
PGP (Personal Genome Project)
n/a public study
1Conditions, genes, variants, underlying research references, and methodology white paper(s) available on public website
Which service to buy?
*Physician prescription required
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Consumer genomics: interpretation variance
Source: www.DIYgenomics.org and Swan, M. Multigenic Condition Risk Assessment in Direct-to-Consumer Genomic Services. Genet. Med. 2010, May;12(5):279-88. Private data upload: Marat Nepomnyashy
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Open-source mobile apps (5,000+ downloads)
Health condition, drug response, athletic performance
23andMe data upload
Android
iPhone
Android development: Michael Kolb, Lawrence S. Wong, Laura Klemme, Melanie SwaniPhone development: Ted Odet, Greg Smith, Laura Klemme, Melanie Swan
“genomics”4,000+ downloads
“genomics”1,000+ downloads
T T T
T T T
T C C
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Citizen science health landscape
Source: Extended from Swan, M. Emerging patient-driven health care models: an examination of health social networks, consumer personalized medicine and quantified self-tracking. Int. J. Environ. Res. Public Health 2009, 2, 492-525.
Health collaboration communities
Health social networks
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Lifecycle of a health condition
Pre-clinical (80%) Clinical (20%)
Preventive medicineLong-tail medicine
Self-trackingWellness profiling
Health community collaborationApplied healthspan engineering
Traditional medicineDisease treatmentMedical expertise
EmergencyExceptions
Time
# conditionsbecoming
clinical
Goal: decrease in clinical conditions over time
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Genome hacking philosophy
Goal: preventive medicine Realize preventive medicine by establishing baseline markers
of wellness and pre-clinical interventions
Generalized hypothesis One or more polymorphisms may result in out-of-bounds
baseline levels of phenotypic markers. These levels may be improved through personalized intervention.
Source: http://diygenomics.pbworks.com/MTHFR
Genotype Phenotype Intervention Outcome+ + =
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Vitamin B deficiency / MTHFR mutation
Do common mutations in the MTHFR gene prevent vitamin B from working correctly?
Test whether 2 variations in the MTHFR gene keep vitamin B9 (folic acid) from being metabolized into its active form (folate) rs1801133/C677T rs1801131/A1298C
Without this form of vitamin B, homocysteine may accumulate (risk of cardiovascular disease, etc.)
50% or more of the population may have some form of MTHFR polymorphism
Source: http://diygenomics.pbworks.com/MTHFR
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Homocysteine metabolism pathway
Source: Swan, M., Hathaway, K., Hogg, C., McCauley, R., Vollrath, A. Citizen science genomics as a model for crowdsourced preventive medicine research. J Participat Med. 2010 Dec 23; 2:e20.
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Vitamin B / MTHFR study protocol
1. Genotype
MTHFR gene SNPs:
rs1801133 (A/G)
rs1801131 (A/G)
2. Phenotype
Blood tests:
B-12 and
Homocysteine
3. Intervention
(2 week periods)
1. B-complex
2. L-methylfolate
3. B-complex + L-methylfolate
Investigate genotype-phenotype linkage and apply interventions to improve phenotypic outcomes
Protocol confirmed with two separate experts in the field
Source: http://diygenomics.pbworks.com/MTHFR
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Vitamin B / MTHFR pilot study results
Drug store vitamin (Centrum) reduced homocysteine levels for 6/7 participants
Blood Test #
2. Homocysteine levels
DIYgenomics MTHFR Vitamin B deficiency study1
1. Genotype profiles
Baseline LMF
Source: Swan, M., Hathaway, K., Hogg, C., McCauley, R., Vollrath, A. Citizen science genomics as a model for crowdsourced preventive medicine research. J Participat Med. 2010 Dec 23; 2:e20.
1Results are not statistically significant and are intended as a pilot demonstration of citizen science genomic studies
Baseline+ LMF
Centrum
Homocysteine umol/l
Centrum
LMF = L-methylfolate
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Personal health collaboration studies
More information: www.DIYgenomics.org www.DIYgenomics.org/DIYgenomics_poster.ppt
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Agenda
Citizen science progress to date
Scaling citizen science
Grand vision next steps
Image credit: http://www.gettyimages.com
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Scaling citizen science
Engaging participants and building trust Innovating the Institutional Review Board Accessing blood tests 2.0 Developing a philosophy of epistemology of citizen
science
Image credit: http://slobodkina.com
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Engaging personal health collaborators
Participation must be fun and easy
Relevant value proposition to target market
Nomenclature framing: enhancement, optimization
Crowdsourcing the value chain: data, questions, financing, analysis
Image credit: http://www.superstock.com
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Athletic performanceCategory Genes V % S
Endurance, power, and energy
Endurance ACE, ACTN3, ADRB2/ ADRB3, BDKRB2, COL5A1, GNB3 7 50 22
Power ACE, ACTN3, AGT 3 50 8
Energy HIF1A, PPARGC1A 3 25 9
Musculature, and heart and lung capacity
Muscle fatigue and repair HNF4A, NAT2 and IL-1B 5 40 4
Strength HFE, HIF1A, IGF1, MSTN GDF8 5 17 15
Heart and lung capacity CREB1, KIF5B, NOS3, NPY and ADRB1, APOE, NRF1 9 36 11
Metabolism, recovery, and other
Metabolism AMPD1, APOA1, PPARA, PPARD 5 50 9
Recovery CKMM/CKM, IL6 2 50 5
Ligament and tendon strength
Ligament strength COL1A1, COL5A1, CILP 3 50 4
Tendon strength COL1A1, COL5A1, GDF5, MMP3 7 63 5
Image credit: http://www.istockphoto.com
V = number of variants; % = ratio of favorable polymorphisms to total alleles for a sample individual; S = number of studies
Source: Swan, M. Applied genomics: personalized interpretation of athletic performance GWAS. Jan 2011.
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Study design template: MTHFR example
Source: http://diygenomics.pbworks.comhttp://diygenomics.pbworks.com/w/file/36469280/DIYgenomics+study+design+template+blank.doc
CyanocobalaminImage credit: http://wikimedia.org
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SponsorsFunders
Study managerGraduate student partner*
Study operation platform
(Genomera)
Study advisors*
Participants
Oversight (IRB)
DIYgenomics study ecosystem – CRO 2.0
* Domain expert
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Health hackers need Blood Tests 2.0
Low-cost home-administered self-read finger-stick blood, urine, saliva tests: Traditional blood tests (Homocysteine, Vitamin B-12, Folate,
Vitamin D, Creatinine, eGFR, Cortisol, Calcium, Iron) Hormones (Estrogen, Progesterone, Testosterone, Estradiol) Immune system: CD4, CD8/CD28 ratio, IL-1, IL-6 Chemical / heavy metal burden: mercury, cadmium, lead, tin
OrSense continuous non-invasive glucose monitoring
Cholestech LDX home cholesterol test
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Towards an epistemology of citizen science
Provide a structure and context for self-derived health knowledge
Q1: Are new kinds of knowledge are being formed through group collaborations such as wikipedia and health social networks?
Q2: Are there differences in the types of knowledge generated by traditional medicine, self-experimentation, and health collaboration communities?
Image credit: http://inkingrey.com
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Ontological shift
Old thinking:
My health is the responsibility of my physician
New thinking:
My health is my responsibility
… and I have the tools to make it fun and easy
Image credit: http://efx3.com
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Citizen science progress to date
Scaling citizen science
Grand vision next steps
Agenda
Image credit: http://www.gettyimages.com
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Personal genome applications
Ancestry Carrier status Disease risk profiling Drug response Athletic performance capability Product response Wellness profiling
Cancer Immune system Aging
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Predictive wellness profiling: cancer
Proto-oncogene/tumor suppressor gene polymorphisms
Source: DIYgenomics
Image credit: http://utmb.edu
Alleles 23andMe alleles
Gene RSID Poss Unf Fav Poss Fav Ex p-value OR Case Ctrl Citation
TP531 rs1042522 CG C G CG G CG 0.77 1.23 685 778 Joshi 2010
TP53 rs1860746 GT T G n/a n/a n/a 0.04 1.47 6,127 5,197 Liu 2009
MDM22 rs2279744 GT G T GT T GT 0.91 1.27 685 778 Joshi 2010
MDM41 rs1380576 CG G C n/a n/a n/a 0.95 1.03 4,073 n/a Sun 2010
HAUSP1 rs1529916 AG G A n/a n/a n/a 0.07 1.05 4,073 n/a Sun 2010
PTEN1 rs701848 CT C T CT T CT 0.00 0.12 53 107 Hosgood 2010
PTEN1 rs1903858 AG G A AG A AA 0.01 0.13 53 107 Hosgood 2010
BCL22 938C>A AC A C n/a n/a n/a 0.05 n/a 40 40 Fingas 2010
GNB32 rs5443 CT T C CT C CC 0.05 n/a 40 40 Fingas 2010
MYC2 rs6983267 GT G T GT T TT 0.00 1.21 930 960 Tomlinson 2007
MYC rs1050477 AC A C GT G GG 0.00 1.17 7,480 7,779 Zanke 2007 MYC rs7014346 AG A G AG G GG 0.00 1.19 14,500 13,294 Tenesa 2008
1Tumor Suppressor, 2Proto-oncogene
TP53: cell cycle arrest, PTEN: cell cycle progression modulator, MYC: cell cycle regulator
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Lung cancer risk and drug response
Risk and drug response for specific cancers
Source: Swan, M. Review of cancer risk prediction in direct-to-consumer genomic services. (poster) Canary Foundation Early Detection Symposium, May 25-27, 2010, Stanford University, Stanford CA.
Image credit: http://www.xianet.net
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Wellness profiling: immune system
Immune system genomic wellness profiling Immune response: T-cell activation
CTLA4, CD226, CD86, IL3
Source: DIYgenomics
Alleles 23andMe alleles
Gene RSID Poss Unf Fav Poss Fav Ex p-value OR Case Ctrl Citation CTLA4 rs231775 A/G A G AG G AA 0.007 0.642 172 145 Duan 2010 CTLA4 rs5742909 C/T C T CT T CC 0.098 0.67 172 145 Duan 2010 CTLA4 rs733618 C/T C T CT T TT 0.041 4.62 269 395 DallaCosta 2010 CD226 rs763361 C/T T C CT C CC 0.000 1.22 1,990 1,642 Dieudé 2010 CD86 rs1129055 A/G G A AG A GG 0.006 0.51 269 395 DallaCosta 2010 IL3 rs181781 A/G A G AG G GG 0.041 0.55 60 270 Lee 2010 IL3 rs2073506 A/G A G CT C CC 0.009 0.32 60 270 Lee 2010 IL3 rs40401 C/T T C CT C CC 0.014 2.18 60 270 Lee 2010
Image credit: http://www.iayork.com
CTLA4: T-cell inhibition; IL3: growth-promoting cytokine
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Aging: TA-65, telomere length & TERC mutation
Herbal supplement TA-65 (astragalus root) taken by 1000 people worldwide. Telomere and immune system benefits in humans published Mar 20111
TERC (RNA gene that extends telomeres) SNPs: rs10511887, rs12696304, rs16847897, rs2293607,
rs610160
1Source: Harley CB, et al. A natural product telomerase activator as part of a health maintenance program. Rejuvenation Res. 2011 Feb;14(1):45-56.
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Aging: applied healthspan engineering
Representative Rational Healthspan Interventions Target=process Intervention
1 Blood pressure Multiple; exercise, dietary, sodium restriction, see RAS (below)2 Heart rate Exercise, vagal nerve stimulation3 Dyslipidemia Fish oil; flaxseed oil, olive oil niacin, statins 4 Renin–angiotensin system (RAS) Exercise, dietary, sodium restriction, ACE inhibitors, ARBs, renin inhibitors5 Medial elastocalcinosis Vitamin K2 6 Glucose homeostasis Exercise, metformin, dietary-caloric restriction 7 mTOR pathway Resveratrol, rapamycin, dietary-caloric restriction 8 Inflammation Aspirin, NF-kB inhibitors (e.g., EGCG, quercetin, etc.) 9 Autophagy Verapamil, trephalose, others
10 Extracellular matrix cross-link Alagebrium, ALT-71111 Chemopreventive Aspirin, bioflavonoids
Source: Larrick JW, Mendelsohn A. Applied Healthspan engineering. Rejuvenation Res. 2010 Apr-Jun;13(2-3):265-80, Table 2.
Legend: ACE, angiotensin converting enzyme; ARBs, angiotensin receptor blockers; EGCG, epigallocatechin 3-gallate; mTOR, mammalian target of rapamycin.
Aging studies need not be longitudinal, current improvements to known biomarkers of aging can be measured Image credit: http://www.gettyimages.com
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Circles of preventive medicine
Individual
2. Preventive CareHealth Social NetworksCitizen Science Studies
Health Advisors
3. Traditional health care system and physicians
1. Automated digital health monitoring
Source: Extended from Swan, M. Emerging patient-driven health care models: an examination of health social networks, consumer personalized medicine and quantified self-tracking. Int. J. Environ. Res. Public Health 2009, 2, 492-525.
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Health self-management
Source: Extended from Swan, M. Emerging patient-driven health care models: an examination of health social networks, consumer personalized medicine and quantified self-tracking. Int. J. Environ. Res. Public Health 2009, 2, 492-525, Figure 1.
Thank you!
Melanie SwanFounder
DIYgenomics650-681-9482
@DIYgenomicswww.DIYgenomics.org
[email protected]: http://slideshare.net/LaBloggaCreative Commons 3.0 license
Collaborators:
Lorenzo Albanello
Janet Chang
Cindy Chen
Jon Dekay
John Furber
Eri Gentry
Kristina Hathaway
Takashi Kido
Laura Klemme
Lucymarie Mantese
Raymond McCauley
Crowd-sourced clinical trialsPersonal genome apps
Louis Nahum
Marat Nepomnyashy
Ted Odet
Roland Parnaso
William Reinhardt
Greg Smith
Aaron Vollrath
Lawrence S. Wong