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DIYgenomics: An Open Platform for Democratizing the Genome

Redesigning biology may be man's ultimate artistic and scientific exploit. The first steps are reading and writing genetic data with DNA sequencing and synthetic biology. Already human genome sequencing costs have declined such that individuals worldwide are accessing their own genomic data, and can explore it through open-source science communities such as DIYgenomics.

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DIYgenomics: An Open Platform for Democratizing the Genome

  1. 1. DIYgenomics: An Open Platform for Democratizing the Genome Melanie Swan, MBA Founder DIYgenomics +1-650-681-9482 @DIYgenomics [email_address] March 7, 2011, San Francisco CA Slides: Personal genome apps Crowd-sourced clinical trials
  2. 2. Agenda <ul><li>Introduction </li></ul><ul><li>Application of personal genomic data </li></ul><ul><li>Patient-organized genomic studies </li></ul><ul><li>Mobile and web apps </li></ul>March 7, 2011 Image credit: Getty Images
  3. 3. About Melanie Swan <ul><li>Founder, DIYgenomics </li></ul><ul><li>Hedge fund manager, futurist </li></ul><ul><li>MBA, Wharton; BA, Georgetown Univ.; Faculty, Singularity University </li></ul><ul><li>Sample publications </li></ul><ul><ul><li>Swan, M. Multigenic Condition Risk Assessment in Direct-to-Consumer Genomic Services. Genet. Med. 2010 , May;12(5):279-88. </li></ul></ul><ul><ul><li>Swan, M. Translational antiaging research. Rejuvenation Res. 2010 , Feb;13(1):115-7. </li></ul></ul><ul><ul><li>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. </li></ul></ul>March 7, 2011
  4. 4. Information transmission eras March 7, 2011 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
  5. 5. DNA sequencing: 10x/yr improvement March 7, 2011 April 1, 2010 Image credit: Dec. 14, 2009
  6. 6. Era of 3 rd and 4 th generation sequencing March 7, 2011 3 rd Gen: Sequencing by Synthesis 2 nd Gen: Parallelized sequencing 1 st Gen: Sanger Sequencing 4 th Gen: Electronic Sequencing Sources:,,,
  7. 7. Agenda <ul><li>Introduction </li></ul><ul><li>Application of personal genomic data </li></ul><ul><li>Patient-organized genomic studies </li></ul><ul><li>Mobile and web apps </li></ul>March 7, 2011 Image credit: Getty Images
  8. 8. Numerous useful applications of genomics <ul><li>Traditional </li></ul><ul><ul><li>Ancestry </li></ul></ul><ul><ul><li>Carrier status </li></ul></ul><ul><ul><li>Identity (paternity, forensics) </li></ul></ul><ul><li>Maturing </li></ul><ul><ul><li>Health condition risk </li></ul></ul><ul><ul><li>Pharmaceutical response </li></ul></ul><ul><li>Novel </li></ul><ul><ul><li>Athletic performance </li></ul></ul><ul><ul><li>OTC product response </li></ul></ul><ul><ul><li>Toxin processing </li></ul></ul><ul><li>Predictive wellness profiling </li></ul><ul><ul><li>Aging, cancer, immune response, organ health </li></ul></ul>March 7, 2011 Image credit:
  9. 9. Interpreting DNA information March 7, 2011 Image credit: 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
  10. 10. Personal genome results March 7, 2011
  11. 11. Example: what to do with your data <ul><li>Check if you have the risk allele for the BDNF gene </li></ul><ul><li>Determine related SNP/rsID#, rs6265 (neuroplasticity) </li></ul><ul><li>Search genomic data for rs6265 genotype (e.g., CC) </li></ul><ul><li>Determine the risk allele (which letter?) (e.g.; G 1 ) </li></ul><ul><li>Opportunity: genomic database with three minimal fields: gene, rsid# and risk allele </li></ul><ul><li>Current genomics search resources </li></ul><ul><ul><li>PharmGKB, dbSNP, GWAS catalog, SNPedia </li></ul></ul>March 7, 2011 Source: 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.
  12. 12. Finding your BDNF data, variant rs6265 March 7, 2011 <ul><li>Consumer genomic services genotype 600,000-1m variants but only map a few up to the annotation browser </li></ul>
  13. 13. Agenda <ul><li>Introduction </li></ul><ul><li>Application of personal genomic data </li></ul><ul><li>Patient-organized genomic studies </li></ul><ul><li>Mobile and web apps </li></ul>March 7, 2011 Image credit: Getty Images
  14. 14. DIYgenomics philosophy March 7, 2011 <ul><li>Goal: preventive medicine </li></ul><ul><ul><li>Realize preventive medicine by establishing baseline markers of wellness and pre-clinical interventions </li></ul></ul><ul><li>Generalized hypothesis </li></ul><ul><ul><li>One or more polymorphisms may result in out-of-bounds baseline levels of phenotypic markers. These levels may be improved through personalized intervention. </li></ul></ul>Source: Genotype Phenotype Intervention Outcome + + =
  15. 15. DIYgenomics study design template March 7, 2011 Source:
  16. 16. DIYgenomics study #1: MTHFR <ul><li>Do common mutations in the MTHFR gene prevent vitamin B from working correctly? </li></ul><ul><li>Test whether 2 variations in the MTHFR gene (methylenetetrahydrofolate reductase) keep vitamin B9 (folic acid) from being metabolized into its active form (folate) </li></ul><ul><ul><li>rs1801133/C677T </li></ul></ul><ul><ul><li>rs1801131/A1298C </li></ul></ul><ul><li>Without this form of vitamin B, homocysteine may accumulate </li></ul><ul><ul><li>Risk: nutritional deficiencies and symptoms associated with diabetes complications, including vascular damage and nerve damage </li></ul></ul><ul><li>50% or more of the population may have some form of MTHFR polymorphism </li></ul>March 7, 2011 Source: Cyanocobalamin Image credit:
  17. 17. Homocysteine metabolism pathway March 7, 2011 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.
  18. 18. MTHFR pilot study results March 7, 2011 <ul><li>Drug store vitamin (Centrum) reduced homocysteine levels for 6/7 participants </li></ul>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
  19. 19. DIYgenomics studies March 7, 2011 Image credit: 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
  20. 20. Memory filtering study March 7, 2011 <ul><li>Dopaminergic modulation of memory filtering </li></ul><ul><li>Collaboration with the Laboratory of Cognitive Neuro-Rehabilitation, University Hospitals of Geneva </li></ul><ul><li>IRB and informed consent </li></ul><ul><li>Goal: 100 member healthy control cohort </li></ul><ul><ul><li>Genotype: COMT, DRD2, SLC6A3 (~5 SNPs) (neurotransmitter modulation) </li></ul></ul><ul><ul><li>Phenotype: memory filtering test (24 minutes) and reversal learning task (10 minutes) </li></ul></ul><ul><ul><li>Background questionnaire: neurological or psychiatric antecedents, medications, demographic information, and IQ (WAIS, Raven’s Matrices) </li></ul></ul>Image credit:
  21. 21. DIYgenomics aging study <ul><li>Genomics + physical biomarkers + intervention </li></ul><ul><li>Top twenty genomic mechanisms of aging </li></ul><ul><ul><li>Aging-specific genetics (IGF signaling, DNA repair, etc.) </li></ul></ul><ul><ul><li>Diabetes and metabolic disease </li></ul></ul><ul><ul><li>Catabolism (waste removal) and other </li></ul></ul><ul><ul><li>Heart disease and blood operations </li></ul></ul><ul><ul><li>Cancer </li></ul></ul><ul><li>Top twenty phenotypic biomarkers of aging </li></ul><ul><li>Interventions </li></ul><ul><ul><li>Traditional </li></ul></ul><ul><ul><li>Novel (example: telomerase activation therapies) </li></ul></ul>March 7, 2011 More information: Image credit:
  22. 22. Innovating the research model March 7, 2011 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
  23. 23. Genomic study platform: Genomera March 7, 2011
  24. 24. Agenda <ul><li>Introduction </li></ul><ul><li>Application of personal genomic data </li></ul><ul><li>Patient-organized genomic studies </li></ul><ul><li>Mobile and web apps </li></ul>March 7, 2011 Image credit: Getty Images
  25. 25. 4,000+ mobile app downloads <ul><li>Health condition, drug response, athletic performance </li></ul><ul><li>23andMe data upload </li></ul><ul><li>Android </li></ul><ul><li>iPhone </li></ul>March 7, 2011 Android development: Michael Kolb, Lawrence S. Wong, Laura Klemme, Melanie Swan iPhone development: Ted Odet, Greg Smith, Laura Klemme, Melanie Swan “ genomics” “ genomics”
  26. 26. Multi-view web app with private data upload March 7, 2011 Private data upload: Marat Nepomnyashy;
  27. 27. Thank you! Melanie Swan Founder DIYgenomics +1-650-681-9482 @DIYgenomics [email_address] Slides: 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
  28. 28. Consumer genomic comparison March 7, 2011 <ul><li>Three companies cover colorectal cancer </li></ul><ul><li>Different genes and variants are reviewed </li></ul>
  29. 29. Drug response March 7, 2011
  30. 30. Ranking variant quality <ul><li>Background </li></ul><ul><ul><li>NIH plan to develop a Genetic Testing Registry (2011) </li></ul></ul><ul><ul><li>Criteria proposed by Ioannidis JP et al. Int J Epidemiol. (2008): amount of evidence, replication, protection from bias </li></ul></ul><ul><li>Methodology: assign a composite score to each variant per the number of cases and controls, p-value, odds ratio, and journal ranking </li></ul>March 7, 2011 Source: DIYgenomics Image credit:
  31. 31. Athletic performance March 7, 2011 Image credit: 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
  32. 32. OTC product response, toxin processing <ul><li>OTC product response </li></ul><ul><ul><li>Skin (premature aging, wrinkles, sun damage, eczema, irritation, antioxidant treatment, anti-aging treatment) </li></ul></ul><ul><ul><li>Hair (hair loss, premature greying, male pattern baldness) </li></ul></ul><ul><ul><li>Esophagus (reflux, bile acid response) </li></ul></ul><ul><ul><li>Teeth (periodontitis) </li></ul></ul><ul><ul><li>Sleep (daytime sleepiness, caffeine-induced insomnia) </li></ul></ul><ul><li>Environmental exposure: toxin processing </li></ul><ul><ul><li>Benzene </li></ul></ul><ul><ul><li>Quinone oxidoreductase </li></ul></ul><ul><ul><li>PAHs metabolism </li></ul></ul><ul><ul><li>Arylarene metabolism </li></ul></ul><ul><ul><li>Mercury and lead exposure </li></ul></ul><ul><ul><li>Liver and kidney health (general) </li></ul></ul>March 7, 2011 Source: DIYgenomics Image credit:
  33. 33. Predictive wellness profiling: cancer <ul><li>Proto-oncogene/tumor suppressor gene polymorphisms </li></ul>March 7, 2011 Source: DIYgenomics Image credit: TP53: cell cycle arrest, PTEN: cell cycle progression modulator, MYC: cell cycle regulator
  34. 34. Lung cancer risk and drug response <ul><li>Risk and drug response for specific cancers </li></ul>March 7, 2011 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:
  35. 35. Wellness profiling: immune system <ul><li>Immune system genomic wellness profiling </li></ul><ul><li>Immune response: T-cell activation </li></ul><ul><ul><li>CTLA4, CD226, CD86, IL3 </li></ul></ul>March 7, 2011 Source: DIYgenomics Image credit: CTLA4: T-cell inhibition; IL3: growth-promoting cytokine
  36. 36. Aging (genomic markers) <ul><li>Top twenty genomic mechanisms of aging (1,000 variants in DIYgenomics Aging GWAS database) </li></ul><ul><ul><li>Aging-specific genetics (overall profile, IGF-1/insulin signaling, inflammation, immune system, DNA damage repair, cell cycle, telomere length, mitochondrial health) </li></ul></ul><ul><ul><li>Diabetes and metabolic disease (cholesterol, obesity, adiposity, fat distribution) </li></ul></ul><ul><ul><li>Catabolism (waste removal) and other (Alzheimer’s disease, macular degeneration, rheumatoid arthritis, osteoporosis, sarcopenia, kidney and liver disease) </li></ul></ul><ul><ul><li>Heart disease and blood operations (cardiovascular disease, atherosclerosis, myocardial infarction, atrial fibrillation) </li></ul></ul><ul><ul><li>Cancer (profile for twenty cancers including breast, prostate, colorectal, lung, melanoma, glioma, ovarian, pancreatic) </li></ul></ul>March 7, 2011 Image credit: Source: DIYgenomics Aging GWAS Database:
  37. 37. Aging (phenotypic markers) <ul><li>Top twenty phenotypic biomarkers of aging </li></ul><ul><ul><li>Aging-specific markers (telomere length, lymphocyte regeneration, CD levels, inflammation, hormone levels) </li></ul></ul><ul><ul><li>Diabetes and metabolic disease (BMI, cholesterol (HDL/LDL/triglycerides; LDL particle size), Framingham Risk Score, fasting glucose, non-fasting glucose, albumin, uric acid) </li></ul></ul><ul><ul><li>Catabolism and other (VO2 max, bone mineral density, muscle mass, GOT, GPT, creatinine, eGFR) </li></ul></ul><ul><ul><li>Heart disease and blood operations (blood pressure, hematocrit, hemoglobin, RBC, WBC, CRP, platelets, erythrocyte glycoslyation) </li></ul></ul><ul><ul><li>Cancer (granulocyte strength, blood-assay) </li></ul></ul>March 7, 2011 Image credit: Source: DIYgenomics Aging Study,
  38. 38. Aging (interventions) <ul><li>Top twenty aging interventions </li></ul><ul><ul><li>Traditional (exercise, nutrition, sleep, vitamins, stress-reduction) </li></ul></ul><ul><ul><li>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) </li></ul></ul>March 7, 2011 Image credit: Source: DIYgenomics Aging Study,
  39. 39. <ul><li>Would you like to know… </li></ul><ul><li>… if your vitamin supplements are effective </li></ul><ul><li>… which vitamin supplements would be effective and best for you </li></ul><ul><li>… personalized interventionswhat conditions you are at higher genetic susceptibility for and are </li></ul><ul><li>… your predictive wellness profile for aging, cancer, immune system response </li></ul>March 7, 2011