DIYgenomics: An Open Platform for Democratizing the Genome

DIYgenomics: An Open Platform for Democratizing the Genome Melanie Swan, MBA Founder DIYgenomics +1-650-681-9482 @DIYgenomics www.DIYgenomics.org [email_address] March 7, 2011, San Francisco CA Slides: http://slideshare.net/LaBlogga Personal genome apps Crowd-sourced clinical trials

Agenda
Introduction
Application of personal genomic data
Patient-organized genomic studies
Mobile and web apps
March 7, 2011 DIYgenomics.org Image credit: Getty Images

About Melanie Swan
Founder, DIYgenomics
Hedge fund manager, futurist
MBA, Wharton; BA, Georgetown Univ.; Faculty, Singularity University
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. 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.
March 7, 2011 DIYgenomics.org

Information transmission eras March 7, 2011 DIYgenomics.org Painting Transistor (1/0) DNA (ACTG) Analog Digital Life code ? 01101 100011011111011101 1 001100101 – I love you 01101 100011011111011101 0 001100101 – I hate you 2010-2100 1950-2010 17,300 years ago

DNA sequencing: 10x/yr improvement March 7, 2011 DIYgenomics.org April 1, 2010 Image credit: http://pubs.acs.org/cen/_img/87/i50/8750cover2_law.gif Dec. 14, 2009

Era of 3 rd and 4 th generation sequencing March 7, 2011 DIYgenomics.org 3 rd Gen: Sequencing by Synthesis 2 nd Gen: Parallelized sequencing 1 st Gen: Sanger Sequencing 4 th Gen: Electronic Sequencing Sources: http://www.genomicseducation.ca/files/images/information_articles/sequencing.gif, http://www.wellcome.ac.uk/News/2009/Features/WTX056032.htm, http://www.pacificbiosciences.com/video_lg.html, http://www.nanoporetech.com/sequences

Agenda
Introduction
Mobile and web apps

Numerous useful applications of genomics
Traditional
Ancestry
Carrier status
Identity (paternity, forensics)
Maturing
Health condition risk
Pharmaceutical response
Novel
Athletic performance
OTC product response
Toxin processing
Predictive wellness profiling
Aging, cancer, immune response, organ health
March 7, 2011 DIYgenomics.org Image credit: http://bit.ly/fovpJc

Interpreting DNA information March 7, 2011 DIYgenomics.org Image credit: http://123RF.com Example: rs1801133 A G AA , A G , GG Allele, variant, SNP (single nucleotide polymorphism); “typo” in red; normal in green A C G T Example: rs7412 C T CC , C T , TT

Personal genome results March 7, 2011 DIYgenomics.org

Example: what to do with your data
Check if you have the risk allele for the BDNF gene
Determine related SNP/rsID#, rs6265 (neuroplasticity)
Search genomic data for rs6265 genotype (e.g., CC)
Determine the risk allele (which letter?) (e.g.; G 1 )
Opportunity: genomic database with three minimal fields: gene, rsid# and risk allele
Current genomics search resources
PharmGKB, dbSNP, GWAS catalog, SNPedia
March 7, 2011 DIYgenomics.org Source: http://www.wired.com/wiredscience/2009/10/genetically-bad-driving 1 Ribeiro, L. et. Al., The brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism and depression in Mexican-Americans. Cellular, Molecular and Developmental Neuroscience. May 8, 2007.

Finding your BDNF data, variant rs6265 March 7, 2011 DIYgenomics.org
Consumer genomic services genotype 600,000-1m variants but only map a few up to the annotation browser

Agenda
Introduction
Mobile and web apps

DIYgenomics philosophy March 7, 2011 DIYgenomics.org
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 + + =

DIYgenomics study design template March 7, 2011 DIYgenomics.org Source: http://diygenomics.pbworks.com/ http://diygenomics.pbworks.com/w/file/36469280/DIYgenomics+study+design+template+blank.doc

DIYgenomics study #1: MTHFR
Do common mutations in the MTHFR gene prevent vitamin B from working correctly?
Test whether 2 variations in the MTHFR gene (methylenetetrahydrofolate reductase) 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: nutritional deficiencies and symptoms associated with diabetes complications, including vascular damage and nerve damage
50% or more of the population may have some form of MTHFR polymorphism
March 7, 2011 DIYgenomics.org Source: http://diygenomics.pbworks.com/MTHFR Cyanocobalamin Image credit: http://wikimedia.org

Homocysteine metabolism pathway March 7, 2011 DIYgenomics.org 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.

MTHFR pilot study results March 7, 2011 DIYgenomics.org
Drug store vitamin (Centrum) reduced homocysteine levels for 6/7 participants
Blood Test # 2. Homocysteine levels DIYgenomics MTHFR Vitamin B deficiency study 1 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. 1 Results are not statistically significant and are intended as a pilot demonstration of patient-organized genomic studies Baseline + LMF Centrum Homocysteine umol/l Centrum LMF = L-methylfolate

DIYgenomics studies March 7, 2011 DIYgenomics.org Image credit: http://www.narsad.org/?q=node/11245 Study Status 1. MTHFR/Vitamin B Pilot complete, open enrollment 2. Memory filtering In design (Q1/Q2) 3. Aging Open enrollment 4. Vitamin D In design (Q2) 5. Mental performance In design (Q3) 6. Metabolism/cholesterol mgt In design (Q3) 7. Citizen scientist proposed… Ongoing

Memory filtering study March 7, 2011 DIYgenomics.org
Dopaminergic modulation of memory filtering
Collaboration with the Laboratory of Cognitive Neuro-Rehabilitation, University Hospitals of Geneva
IRB and informed consent
Goal: 100 member healthy control cohort
Genotype: COMT, DRD2, SLC6A3 (~5 SNPs) (neurotransmitter modulation)
Phenotype: memory filtering test (24 minutes) and reversal learning task (10 minutes)
Background questionnaire: neurological or psychiatric antecedents, medications, demographic information, and IQ (WAIS, Raven’s Matrices)
Image credit: http://bit.ly/g2DIcW

DIYgenomics aging study
Genomics + physical biomarkers + intervention
Top twenty genomic mechanisms of aging
Aging-specific genetics (IGF signaling, DNA repair, etc.)
Diabetes and metabolic disease
Catabolism (waste removal) and other
Heart disease and blood operations
Cancer
Top twenty phenotypic biomarkers of aging
Interventions
Traditional
Novel (example: telomerase activation therapies)
March 7, 2011 DIYgenomics.org More information: http://diygenomics.pbworks.com/Aging Image credit: http://www-nmr.cabm.rutgers.edu

Innovating the research model March 7, 2011 DIYgenomics.org Institutional PI (principal investigator) Traditional Research Model Patient-organized Research Model Research subjects Citizen scientists* Investigators = Participants *Self-selection bias: 100,000 consumer genomics customers Institutional Review Board (IRB) IRBs, FAQs, Citizen ethicists Grant funding Journal publication Self publishing Patient advocacy groups Research foundations Social VC Crowd-sourcing

Genomic study platform: Genomera March 7, 2011 DIYgenomics.org

Agenda
Introduction
Mobile and web apps

4,000+ mobile app downloads
Health condition, drug response, athletic performance
23andMe data upload
Android
iPhone
March 7, 2011 DIYgenomics.org Android development: Michael Kolb, Lawrence S. Wong, Laura Klemme, Melanie Swan iPhone development: Ted Odet, Greg Smith, Laura Klemme, Melanie Swan “ genomics” “ genomics”

Multi-view web app with private data upload March 7, 2011 DIYgenomics.org Private data upload: Marat Nepomnyashy; https://addons.mozilla.org/en-US/firefox/addon/156946

Thank you! Melanie Swan Founder DIYgenomics +1-650-681-9482 @DIYgenomics www.DIYgenomics.org [email_address] Slides: http://slideshare.net/LaBlogga Creative Commons 3.0 license Collaborators: Lorenzo Albanello Cindy Chen John Furber Hong Guo Kristina Hathaway Laura Klemme Priya Kshirsagar Lucymarie Mantese Raymond McCauley Marat Nepomnyashy Ted Odet Roland Parnaso William Reinhardt Greg Smith Aaron Vollrath Lawrence S. Wong International collaborations: JST and Rikengenesis Takashi Kido Minae Kawashima Jin Yamanaka University Hospitals of Geneva Louis Nahum Armin Schnider Personal genome apps Crowd-sourced clinical trials

Consumer genomic comparison March 7, 2011 DIYgenomics.org
Three companies cover colorectal cancer
Different genes and variants are reviewed

Drug response March 7, 2011 DIYgenomics.org

Ranking variant quality
Background
NIH plan to develop a Genetic Testing Registry (2011)
Criteria proposed by Ioannidis JP et al. Int J Epidemiol. (2008): amount of evidence, replication, protection from bias
Methodology: assign a composite score to each variant per the number of cases and controls, p-value, odds ratio, and journal ranking
March 7, 2011 DIYgenomics.org Source: DIYgenomics Image credit: http://www.evexiscy.com

Athletic performance March 7, 2011 DIYgenomics.org 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. 2011 Jan. Submitted. Category 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

OTC product response, toxin processing
OTC product response
Skin (premature aging, wrinkles, sun damage, eczema, irritation, antioxidant treatment, anti-aging treatment)
Hair (hair loss, premature greying, male pattern baldness)
Esophagus (reflux, bile acid response)
Teeth (periodontitis)
Sleep (daytime sleepiness, caffeine-induced insomnia)
Environmental exposure: toxin processing
Benzene
Quinone oxidoreductase
PAHs metabolism
Arylarene metabolism
Mercury and lead exposure
Liver and kidney health (general)
March 7, 2011 DIYgenomics.org Source: DIYgenomics Image credit: http://sciencephoto.com

Predictive wellness profiling: cancer
Proto-oncogene/tumor suppressor gene polymorphisms
March 7, 2011 DIYgenomics.org Source: DIYgenomics Image credit: http://utmb.edu 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
March 7, 2011 DIYgenomics.org 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
March 7, 2011 DIYgenomics.org Source: DIYgenomics Image credit: http://www.iayork.com CTLA4: T-cell inhibition; IL3: growth-promoting cytokine

Aging (genomic markers)
Top twenty genomic mechanisms of aging (1,000 variants in DIYgenomics Aging GWAS database)
Aging-specific genetics (overall profile, IGF-1/insulin signaling, inflammation, immune system, DNA damage repair, cell cycle, telomere length, mitochondrial health)
Diabetes and metabolic disease (cholesterol, obesity, adiposity, fat distribution)
Catabolism (waste removal) and other (Alzheimer’s disease, macular degeneration, rheumatoid arthritis, osteoporosis, sarcopenia, kidney and liver disease)
Heart disease and blood operations (cardiovascular disease, atherosclerosis, myocardial infarction, atrial fibrillation)
Cancer (profile for twenty cancers including breast, prostate, colorectal, lung, melanoma, glioma, ovarian, pancreatic)
March 7, 2011 DIYgenomics.org Image credit: http://reisearch.net/biotech_page/dna_horizontal.gif Source: DIYgenomics Aging GWAS Database: http://bit.ly/fDobgO

Aging (phenotypic markers)
Top twenty phenotypic biomarkers of aging
Aging-specific markers (telomere length, lymphocyte regeneration, CD levels, inflammation, hormone levels)
Diabetes and metabolic disease (BMI, cholesterol (HDL/LDL/triglycerides; LDL particle size), Framingham Risk Score, fasting glucose, non-fasting glucose, albumin, uric acid)
Catabolism and other (VO2 max, bone mineral density, muscle mass, GOT, GPT, creatinine, eGFR)
Heart disease and blood operations (blood pressure, hematocrit, hemoglobin, RBC, WBC, CRP, platelets, erythrocyte glycoslyation)
Cancer (granulocyte strength, blood-assay)
March 7, 2011 DIYgenomics.org Image credit: http://reisearch.net/biotech_page/dna_horizontal.gif Source: DIYgenomics Aging Study, http://diygenomics.pbworks.com/w/page/30326105/Aging

Aging (interventions)
Top twenty aging interventions
Traditional (exercise, nutrition, sleep, vitamins, stress-reduction)
Novel (brain fitness programs and mid-life cholesterol management for Alzheimer’s disease, cholesterol management with CETP-inhibitor a nacetrapib, TA-65 telomerase activation for telomere length management, resistance weight lifting for sarcopenia, interval training and aerobic exercise for VO2 max improvement, blood-based assays for early detection of cancer, rheumatoid arthritis, macular degeneration, kidney and liver disease)
March 7, 2011 DIYgenomics.org Image credit: http://reisearch.net/biotech_page/dna_horizontal.gif Source: DIYgenomics Aging Study, http://diygenomics.pbworks.com/w/page/30326105/Aging

Would you like to know…
… if your vitamin supplements are effective
… which vitamin supplements would be effective and best for you
… personalized interventionswhat conditions you are at higher genetic susceptibility for and are
… your predictive wellness profile for aging, cancer, immune system response
March 7, 2011 DIYgenomics.org

DIYgenomics: An Open Platform for Democratizing the Genome

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