Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Personal Genomes: what can I do with my data?


Published on

Biology evolved to be just good enough to survive and genomics provides the critical next-generation toolkit for its greater exploitation. Genomics is already starting to be medically actionable and is likely to become increasingly useful over time. This presentation discusses how your genetic information is already useful today,

Published in: Technology

Personal Genomes: what can I do with my data?

  1. 1. Revolutionizing Biology with Personal Genomes Melanie Swan Research Fellow MS Futures Group +1-650-681-9482 @LaBlogga [email_address] March 26, 2010 NASA AMES Project information: Slides: Image credit:
  2. 2. Agenda <ul><li>Consumer genomic landscape </li></ul><ul><li>DNA sequencing technology </li></ul><ul><li>DIYgenomics citizen science </li></ul> Image credit:
  3. 3. Numerous useful applications of genomics <ul><li>Ancestry </li></ul><ul><li>Pharmaceutical response </li></ul><ul><li>Health conditions </li></ul><ul><li>Pregnancy screening </li></ul><ul><ul><li>Prenatal, preconception </li></ul></ul><ul><li>Identity (paternity, forensics) </li></ul><ul><li>Athletic capability and training </li></ul><ul><ul><li>MMP3 (Achilles tendon) </li></ul></ul><ul><ul><li>COL1A1 (collagen, ACL) </li></ul></ul> Reference: “Cheating is so 1999: A reporter spends a year searching for the athletic holy grail: a sports gene,” Assael , Shaun, ESPN The Magazine, Oct. 6, 2009,
  4. 4. Direct-to-Consumer genomics landscape $2,500 $999 Single/few condition Multiple condition Whole genome Cost 1 Whole genome: $68,500; exome: $24,500 Offering Breadth Public studies (specific diseases or traits) (common diseases) Matchmaking ScientificMatch $1,995 GenePartner $10-$99 Paternity Genelex $200-$475 Identigene $149-$399 Pregnancy Screening Counsyl $349 Nutrigenomics APO E Gene Diet $389 Inherent Health $99 Coriell 15 conditions Scripps (Navigenics) 28 conditions Pers. Genome Proj. Conditions undisclosed Harvard Med. Sch. Genetic disorders, Predisposition DNA Direct $200-$3,500 Matrix Genomics $199-$799 Drug sensitivity, Knome Illumina $48,000 $350,000 $99,500 $68,500 1 23andme 141 conditions Navigenics 28 conditions Gene Essence 84 conditions $1,000 $429 Genome-wide health offerings $2,000 $1,195 $299 Genomics 71 conditions Pathway $ deCODEme 49 conditions $985
  5. 5. Example: Breast cancer – Navigenics Source:
  6. 6. Example: Breast cancer – deCODEme Source:
  7. 7. Example: Breast cancer – 23andme Source:
  8. 8. Example: Breast cancer – Pathway Genomics Source:
  9. 9. Side-by-side comparison: breast cancer <ul><li>22 Variants at 15 loci are reviewed </li></ul> Source:, Markers reviewed by consumer genomic services for breast cancer
  10. 10. Why risk interpretation can vary by consumer genomic service <ul><li>Companies are using different… </li></ul><ul><ul><li>Average lifetime risks for the same underlying population </li></ul></ul><ul><ul><li>SNP/loci selection criteria </li></ul></ul><ul><ul><li>Quantitative risk assignment methodologies </li></ul></ul> Source: Swan, M. Multigenic Condition Risk Assessment in Direct-to-Consumer Genomic Services. Genet. Med. 2010, in press. Image credit:
  11. 11. 1. Differences in population average lifetime risk Source: Swan, M. Multigenic Condition Risk Assessment in Direct-to-Consumer Genomic Services. Genet. Med. 2010, in press. Population average lifetime risk in DTC genomic services
  12. 12. 2. Differences in SNP/loci selection criteria <ul><li>Less than a quarter of all loci (22%) are being reviewed by the three biggest companies </li></ul> Source: Swan, M. Multigenic Condition Risk Assessment in Direct-to-Consumer Genomic Services. Genet. Med. 2010, in press. Loci overlap for three DTC Genomic Companies
  13. 13. 3. Differences in risk assignment methodology <ul><li>Relative risk assignment per SNP </li></ul><ul><ul><li>Debate: include only strong-effect markers </li></ul></ul><ul><li>Composite risk assignment per condition </li></ul> Source: Swan, M. Multigenic Condition Risk Assessment in Direct-to-Consumer Genomic Services. Genet. Med. 2010, in press. Risk Allele Quantification by DTC Genomic Companies
  14. 14. Genomics comparison scorecard 1 Conditions, genes, variants, underlying research references, and methodology white paper(s) available on public website <ul><li>Which service to buy? </li></ul>Consumer genomic service # Cond-itions Cost Report Data access Visible research quality 1 Updates deCODEme 49 $2,000  +   +  + 23andme 141 $429     Navigenics 28 $999    Pathway Genomics 71 $299  Gene Essence 84 $1,195 Coriell 7-15 public study PGP (Personal Genome Project) n/a public study
  15. 15. Consumer resource: <ul><li>Information on genetic tests from 65 companies </li></ul>
  16. 16. genomics comparison <ul><li>PersonalGenomics Android app and web app </li></ul> 1. 20 conditions 2. Locus/SNP detail 3. Reference detail 4. PubMed detail Application developed by: Michael Kolb, Lawrence S. Wong, Melanie Swan Source:
  17. 17. Agenda <ul><li>Consumer genomic landscape </li></ul><ul><li>DNA sequencing technology </li></ul><ul><li>DIYgenomics citizen science </li></ul> Image credit:
  18. 18. Early sequencing technology <ul><li>Sanger sequencing (chain termination) </li></ul><ul><ul><li>Make millions of different-length copies </li></ul></ul><ul><ul><li>Print on electrophoresis gel </li></ul></ul><ul><ul><ul><li>Read lengths small to large </li></ul></ul></ul><ul><ul><ul><li>Fluorescent indicators denote bases </li></ul></ul></ul><ul><ul><li>Reassemble small segments with shotgun sequencing </li></ul></ul> Sources:,
  19. 19. Contemporary (2 nd -gen) sequencing technology <ul><li>Illumina Solexa, ABI SOLiD, 454 </li></ul><ul><li>Illumina example </li></ul><ul><ul><li>Attach adaptors to short sequences </li></ul></ul><ul><ul><li>Amplify by growing clusters </li></ul></ul><ul><ul><li>Add nucleotides, primers </li></ul></ul><ul><ul><li>Activate a laser to read bases as incorporated </li></ul></ul><ul><ul><li>Assemble clusters simultaneously </li></ul></ul><ul><li>Improved read time </li></ul><ul><ul><li>Two gigabases/day at $0.001 per 1000 bases vs. Sanger sequencing (one year at $0.10 per 1000 bases) </li></ul></ul><ul><ul><li>Hiseq (Jan 2010): 25 gigabases/day </li></ul></ul> Source: Illumina sequencing 1 2 3
  20. 20. 3 rd -generation sequencing <ul><li>Sequencing by synthesis pyrosequencing example: Pacific Biosciences SMRT (30,000-fold improvement) </li></ul> Sources:,, Science 2 January 2009: Vol. 323. no. 5910, pp. 133 – 138, DOI: 10.1126/science.1162986 Phospholinked nucleotides DNA polymerase wrapped around DNA chain Label fluoresces as cleaved 1 2 3 Zero-mode waveguide reads sequence 4
  21. 21. 4 th -generation sequencing technology <ul><li>Electronic sequencing </li></ul><ul><ul><li>Ion Torrent, NABsys, Oxford Nanopore Technologies, Agilent, Sequenom, IBM </li></ul></ul><ul><li>Electron microscope reads </li></ul><ul><ul><li>ZS Genetics, Halcyon Molecular </li></ul></ul><ul><li>George Church’s list of next-gen sequencing technologies </li></ul><ul><ul><li> </li></ul></ul> Sources:, Oxford Nanopore Technologies Ion Torrent
  22. 22. DNA sequencing and genetic variation <ul><li>Genome </li></ul><ul><ul><li>3 billion base pairs </li></ul></ul><ul><li>Variation #1: SNP differences (single nucleotide polymorphism) </li></ul><ul><ul><li>Little variation (0.1%) </li></ul></ul><ul><li>Variation #2: structural </li></ul><ul><ul><li>Significant variation (12%) </li></ul></ul><ul><ul><li>Copy-number variation </li></ul></ul><ul><ul><li>Insertions </li></ul></ul><ul><ul><li>Deletions </li></ul></ul><ul><ul><li>Inversions </li></ul></ul>Image credit:
  23. 23. Contemporary research in genomics <ul><li>Copy number variation (CNV) </li></ul><ul><li>Cancer </li></ul><ul><li>Pharmacogenomics </li></ul><ul><li>Aging </li></ul><ul><li>Microbiome </li></ul><ul><li>Individual, family, community medical records </li></ul>Image credit:
  24. 24. Moore’s Law in life sciences: Carlson curves <ul><li>Killer apps of DNA: </li></ul><ul><li>Sequencing </li></ul><ul><ul><li>(reading) </li></ul></ul><ul><li>Synthesizing </li></ul><ul><ul><li>(writing) </li></ul></ul>Source:
  25. 25. Agenda <ul><li>Consumer genomic landscape </li></ul><ul><li>DNA sequencing technology </li></ul><ul><li>DIYgenomics citizen science </li></ul> Image credit:
  26. 26. 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> 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.
  27. 27. Finding your BDNF data, variant rs6265 <ul><li>Consumer genomic services genotype 600,000-1m variants but only map a few up to the annotation browser </li></ul>
  28. 28. Consumer genomics enables peer research
  29. 29. 15 citizen science genomic projects
  30. 30. Project #1: MTHFR mutation & Vit B12 deficiency
  31. 31. Project #2: Longevity and genomics BU Centenarian study, Alzheimer’s disease Source: Green RC, Roberts JS. The Impact and Utility of Personalized Genomic Information: Insights from the REVEAL Study. Page 30. Consumer Genetics Show. Hynes Convention Center, Boston, MA, June 9-11, 2009. <ul><li>No clinical treatment currently available </li></ul><ul><li>ε4 positive participants reported health behavior changes </li></ul>
  32. 32. DIYbio: self-genotyping DNA Extraction Sources:,, DNA 2.0 Gene Designer,, DNA Design Melaminometer Hemochromatosis self-test Katherine Aull
  33. 33. Next-generation citizen science <ul><li>Exome cohort, RNA sequencing of mutations </li></ul><ul><li>Infer copy number variation from sequence/genotype </li></ul><ul><li>Algorithm/artificial intelligence (NLP) projects </li></ul><ul><ul><li>Generate phenotypic databases (e.g.; Framingham data) </li></ul></ul><ul><ul><li>Generate core SNP list by condition using algorithms </li></ul></ul><ul><ul><li>Spider Pubmed for all SNPs related to conditions </li></ul></ul><ul><li>‘ Environmentome’ projects </li></ul><ul><ul><li>Cancer maps and EPA data meets web 2.0 & mobiletech </li></ul></ul><ul><ul><li>Personal screening apps (environmentome & microbiome) </li></ul></ul> Microbiome Phenotype Environment Genotype Preventive medicine health data streams
  34. 34. Societal impact of genomics <ul><li>Good & bad sides of newtech </li></ul><ul><ul><li>First trimester sex determination </li></ul></ul><ul><ul><li>Counsyl: hearing loss condition </li></ul></ul><ul><li>“ Pathologizing” new classes of conditions </li></ul><ul><ul><li>Discovery/cure lag </li></ul></ul><ul><li>Genetic privacy: ‘the real identity theft’ </li></ul><ul><ul><li>GINA </li></ul></ul><ul><li>Adoption/non-adoption ethics of radical enhancement technologies </li></ul> Image credit: &quot;Primo Posthuman“, Natasha Vita-More, 1997.
  35. 35. Personal genome analysis startups / tools <ul><li>Crossbow (UMD/College Park, MD): a scalable software pipeline for whole genome resequencing analysis </li></ul><ul><li>DNA Guide (Sebastopol, CA): GIS technology used to create a personal ‘Goolge Earth map’ of the genome </li></ul><ul><li>DNAnexus (Palo Alto, CA): web technologies on a cloud computing infrastructure to create a compute platform for the genome era </li></ul><ul><li>Genomera (Sunnyvale, CA): Personal genomics community (“genomes like me”) </li></ul><ul><li>GenoViz ( Tools for genomic data visualization </li></ul><ul><li>SNP Dr. from DNA Electronics (London, UK): SNP Dr. hand-held lab-on-a-chip device for point-of-care SNP sequencing in 15-30 minutes to evaluate patient drug response </li></ul><ul><li>HolGenTech (Sunnyvale, CA): Android application using genetic markers for nutrition choice, video . </li></ul><ul><li>SNPedia (Maryland & the Netherlands): Open-source database for genome sharing and genome interpretation via Promethease report </li></ul><ul><li>Portable Genomics (France): smartphone genome browser </li></ul> Sources:
  36. 36. Resources <ul><ul><li>Consumer genomic resources </li></ul></ul><ul><ul><ul><li> </li></ul></ul></ul><ul><ul><ul><li> </li></ul></ul></ul><ul><ul><li>Genomics 101 </li></ul></ul><ul><ul><ul><li> </li></ul></ul></ul><ul><ul><li>Conferences, podcasts and video </li></ul></ul><ul><ul><ul><li> </li></ul></ul></ul><ul><ul><ul><li> </li></ul></ul></ul><ul><ul><li>DIYbio meetup, email list, resources </li></ul></ul><ul><ul><ul><li> </li></ul></ul></ul><ul><ul><ul><li> </li></ul></ul></ul><ul><ul><ul><li> </li></ul></ul></ul><ul><ul><li>Public genomic studies </li></ul></ul><ul><ul><ul><li> </li></ul></ul></ul><ul><ul><ul><li> </li></ul></ul></ul> Image credit:
  37. 37. Thank you! Melanie Swan Research Fellow MS Futures Group +1-650-681-9482 @LaBlogga [email_address] Slides: Creative Commons 3.0 license Image credit: