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DIYgenomics Open-source preventive medicine and scaling citizen science genomics. Melanie Swan Founder DIYgenomics 415-505-4426 @DIYgenomics www.DIYgenomics.org [email protected]. July 28, 2011, OSCON, Portland OR Slides: http://slideshare.net/LaBlogga. About Melanie Swan. - PowerPoint PPT Presentation
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DIYgenomicsOpen-source preventive medicine and
scaling citizen science genomics
Melanie Swan Founder
DIYgenomics415-505-4426
@DIYgenomics www.DIYgenomics.org
July 28, 2011, OSCON, Portland OR
Slides: http://slideshare.net/LaBlogga
2July 28, 2011DIYgenomics.org
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
3July 28, 2011DIYgenomics.org
Biology is an information technology
011011000110111110111011001100101 – I love you
011011000110111110111010001100101 – I hate you
Image credit: http://pubs.acs.org/cen/_img/87/i50/8750cover2_law.gif Dec. 14, 2009
Image credit: http://www.nanoporetech.com/sequences
4July 28, 2011DIYgenomics.org
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
5July 28, 2011DIYgenomics.org
Agenda
Citizen science progress to date
Scaling citizen science
Grand vision next steps
Image credit: http://www.gettyimages.com
6July 28, 2011DIYgenomics.org
Citizen science definition
Traditional science research
DIYbio
Citizen science: 200+ organizations1
1http://scienceforcitizens.net/finder
Investigation without professional training
7July 28, 2011DIYgenomics.org
Politics of personalized genomics
Genetic Information Nondiscrimination Act (GINA) 2008 Our world is not Gattaca Genomic test regulation expected Genomic rights 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
8July 28, 2011DIYgenomics.org
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
$10,0001
$39,500
9July 28, 2011DIYgenomics.org
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 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?
10July 28, 2011DIYgenomics.org
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
11July 28, 2011DIYgenomics.org
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”
“genomics”
T T T
T T T
T C C
12July 28, 2011DIYgenomics.org
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
13July 28, 2011DIYgenomics.org
Lifecycle of a health condition
Pre-clinical (80%) Clinical (20%)
Preventive medicineSelf-tracking
Wellness profilingHealth community collaborationApplied healthspan engineering
Traditional medicineDisease treatmentMedical expertise
EmergencyExceptions
Time
# conditionsbecoming
clinical
Goal: decrease in clinical conditions over time
14July 28, 2011DIYgenomics.org
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+ + =
15July 28, 2011DIYgenomics.org
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
16July 28, 2011DIYgenomics.org
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.
17July 28, 2011DIYgenomics.org
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
18July 28, 2011DIYgenomics.org
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
19July 28, 2011DIYgenomics.org
Personal health collaboration studies
More information: www.DIYgenomics.org www.DIYgenomics.org/DIYgenomics_poster.ppt
20July 28, 2011DIYgenomics.org
Agenda
Citizen science progress to date
Scaling citizen science
Grand vision next steps
Image credit: http://www.gettyimages.com
21July 28, 2011DIYgenomics.org
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
22July 28, 2011DIYgenomics.org
Engaging personal health collaborators
Participation must be fun and easy
Relevant value proposition to target market
Crowdsourcing the value chain: data, questions, financing, analysis
Nomenclature framing: enhancement, optimization
Image credit: http://www.superstock.com
23July 28, 2011DIYgenomics.org
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.
24July 28, 2011DIYgenomics.org
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
25July 28, 2011DIYgenomics.org
SponsorsFunders
Study managerGraduate student partner*
Study operation platform
(Genomera)
Study advisors*
Participants
Oversight
DIYgenomics study ecosystem – CRO 2.0
* Domain expert
26July 28, 2011DIYgenomics.org
Innovating the research model
Institutional PI (principal
investigator)
Traditional Research Model Citizen Science Research Model
Research subjects
Citizen scientists
Investigators = Participants
Institutional Review Board
(IRB)
Citizen ethicistsFAQs
Grant funding
Journal publication
Self publishing
Patient advocacy
groups
Research foundations
Social VC
Crowd-sourcing
27July 28, 2011DIYgenomics.org
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, Aldosterone)
Hormones (Estrogen, Progesterone, Testosterone, Estradiol)
Immune system: CD4, CD8/CD28 ratio, IL-1, IL-6 Chemical / heavy metal burden: mercury, cadmium,
lead, tin
28July 28, 2011DIYgenomics.org
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
29July 28, 2011DIYgenomics.org
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
30July 28, 2011DIYgenomics.org
Citizen science progress to date
Scaling citizen science
Grand vision next steps
Agenda
Image credit: http://www.gettyimages.com
31July 28, 2011DIYgenomics.org
Preventive wellness
Personal uses of the personal genome Ancestry Carrier status Disease risk profiling Drug response Athletic performance capability Product response
Wellness profiling Cancer Immune system Aging
32July 28, 2011DIYgenomics.org
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
33July 28, 2011DIYgenomics.org
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
34July 28, 2011DIYgenomics.org
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
35July 28, 2011DIYgenomics.org
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 2011.1
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.
36July 28, 2011DIYgenomics.org
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.
37July 28, 2011DIYgenomics.org
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.
38July 28, 2011DIYgenomics.org
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
DIYgenomics415-505-4426
@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