DIYgenomics Open-source preventive medicine and scaling citizen science genomics

DIYgenomicsOpen-source preventive medicine and

scaling citizen science genomics

Melanie Swan Founder

DIYgenomics415-505-4426

@DIYgenomics www.DIYgenomics.org

[email protected]

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


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


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


Agenda

Citizen science progress to date

Scaling citizen science

Grand vision next steps

Image credit: http://www.gettyimages.com


Citizen science definition

Traditional science research

DIYbio

Citizen science: 200+ organizations1

1http://scienceforcitizens.net/finder

Investigation without professional training


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


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


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?


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


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


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


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


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+ + =


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



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.


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



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


Personal health collaboration studies

More information: www.DIYgenomics.org www.DIYgenomics.org/DIYgenomics_poster.ppt


Agenda







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


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


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.


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


SponsorsFunders

Study managerGraduate student partner*

Study operation platform

(Genomera)

Study advisors*

Participants

Oversight

DIYgenomics study ecosystem – CRO 2.0

* Domain expert


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


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


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


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





Agenda



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


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


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


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


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.


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.


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.


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

Documents

DIYgenomics Open-source preventive medicine and scaling citizen science genomics