personal genomes: what can i do with my data?
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Revolutionizing Biology with Personal Genomes
Melanie Swan Research Fellow
MS Futures Group+1-650-681-9482
@LaBloggam@melanieswan.com
www.melanieswan.com
March 26, 2010 NASA AMES
Project information: DIYgenomics.org
Slides: http://slideshare.net/LaBlogga/slideshows
Image credit: http://www-nmr.cabm.rutgers.edu/photogallery/proteins/gif/dna.gif
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Agenda
Consumer genomic landscape DNA sequencing technology DIYgenomics citizen science
Image credit: http://current.com/1u8qe4c
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Numerous useful applications of genomics
Ancestry Pharmaceutical response Health conditions Pregnancy screening
Prenatal, preconception
Identity (paternity, forensics) Athletic capability and training
MMP3 (Achilles tendon) COL1A1 (collagen, ACL)
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,
http://www.genome.duke.edu/education/seminars/journal-club/documents/Assael_2009.pdf
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Direct-to-Consumer genomics landscape
Single/few condition Multiple condition Whole genome
Cost
1Whole genome: $68,500; exome: $24,500
OfferingBreadth
Public studies
(specific diseases or traits) (common diseases)
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,
Knome
Illumina$48,000
$350,000
$99,500
$68,5001
23andme141 conditions
Navigenics28 conditions
Gene Essence84 conditions
$1,000
$429
Genome-wide health offerings
$2,000
$1,195
$299
Genomics71 conditions
Pathway
$
deCODEme 49 conditions
$985
$2,500
$999
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Example: Breast cancer – Navigenics
Source: http://www.navigenics.com/demo/for_scientists/d/breast_cancer
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Example: Breast cancer – deCODEme
Source: http://demo.decodeme.com/health-watch/details/BCRS
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Example: Breast cancer – 23andme
Source: https://www.23andme.com/you/journal/breastcancer/techreport
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Example: Breast cancer – Pathway Genomics
Source: https://www.pathway.com
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Side-by-side comparison: breast cancer
22 Variants at 15 loci are reviewed
Source: http://www.diygenomics.org/, http://melanieswan.com/documents/multigenic_analysis.xls
Markers reviewed by consumer genomic services for breast cancer
Locus Gene Variant D N 23 PG D N 23
1p11.2 rs11249433 X #102q33.1 CASP8 rs1045485 X X #22q33.1 CASP8 rs17468277 X #22q35 rs13387042 X X X #8 #83p24.1 NEK10 rs4973768 X #15q11.2 MAP3K1 rs4700485 X #45q11.2 MAP3K1 rs889312 X X #45p12 MRPS30 rs4415084 X #95p12 MRPS30 rs10941679 X6q25.1 ESR1 rs2046210 X7q21.2 AKAP9 rs6964587 X8q24 rs672888 X #48q24.21 rs13281615 X X #410q26.13 FGFR2 rs2981582 X X #4 #410q26.13 FGFR2 rs1219648 X X #3,4,5,610q26.13 FGFR2 rs2420946 X #3,4,5,611p15.5 LSP1 rs3817198 X X X #4 #414q24.1 RAD51L1 rs999737 X #1016q12.1 TNRC9 rs3803662 X X X X #8 #8 #4,7,816p12.1 PALB2 1592delT X17q22 COX11 rs7222197 X #122q12.1 CHEK2 1100delC X
15 22 12 7 3 12 6 3 6Legend: D = deCODEme, N = Navigenics, 23 = 23andme, PG = Pathway Genomics
Reference studies
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Why risk interpretation can vary by consumer genomic service
Companies are using different…
Average lifetime risks for the same underlying population
SNP/loci selection criteria
Quantitative risk assignment methodologies
Source: Swan, M. Multigenic Condition Risk Assessment in Direct-to-Consumer Genomic Services. Genet. Med. 2010, in press.
Image credit: http://www.tigerteamconsulting.com/TTC_Site/sectors_binf.jsp
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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. http://melanieswan.com/documents/multigenic_analysis.xls
Population average lifetime risk in DTC genomic services
N D 2 N D 21 Abdominal aneurysm 3% 17% n/a 2% 5% n/a2 Age-related macular degeneration 3% 8% 7% 3% 8% 7%3 Alzheimer's disease 9% 6% n/a 17% 12% n/a4 Atrial fibrillation 26% 25% n/a 23% 25% n/a5 Brain aneurysm 1% 5% n/a 1% 5% n/a6 Breast cancer n/a n/a n/a 13% 12% 13%7 Celiac disease 0% 1% 0% 0% 1% 0%8 Colon cancer 6% 6% 6% 5% 6% 4%9 Crohn's disease 1% 1% 1% 1% 1% 0%
10 Diabetes, type 1 0% n/a 1% 0% n/a 1%11 Diabetes, type 2 25% 25% 24% 30% 28% 18%12 Glaucoma 1% 15% 1% 2% 15% 1%13 Graves' disease 1% n/a n/a 2% n/a n/a14 Heart attack 42% 42% 21% 25% 25% 7%15 Lung cancer 8% 17% 9% 6% 12% 6%16 Lupus 0% n/a 0% 0% n/a 0%17 Melanoma 4% n/a n/a 3% n/a n/a18 Multiple sclerosis 0% 0% 0% 1% 1% 1%19 Obesity 34% 40% 64% 32% 40% 59%20 Osteoarthritis 40% n/a n/a 47% n/a n/a21 Prostate cancer 17% 16% 18% n/a n/a n/a22 Psoriasis 4% 2% 11% 4% 2% 10%23 Restless legs syndrome 4% 7% 2% 4% 13% 4%24 Rheumatoid arthritis 2% 1% 2% 3% 1% 4%25 Ulcerative Colitis n/a 1% 1% n/a 1% 1%26 Venous Thromboembolism 3% 10% 12% 4% 8% 10%
Sources: Legend: http://demo.decodeme.com/summary-report.pdf N Navigenicshttps://www.23andme.com/you/journal/heartattack/overview/ (etc.) D deCODEmehttp://www.navigenics.com/demo 2 23andmePopulation average lifetime risk not available for other DTC companies
Male Female
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2. Differences in SNP/loci selection criteria
Less than a quarter of all loci (22%) are being reviewed by the three biggest companies
Source: Swan, M. Multigenic Condition Risk Assessment in Direct-to-Consumer Genomic Services. Genet. Med. 2010, in press. http://melanieswan.com/documents/multigenic_analysis.xls
Loci overlap for three DTC Genomic Companies
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3. Differences in risk assignment methodology
Relative risk assignment per SNP Debate: include only strong-effect markers
Composite risk assignment per condition
Risk Allele Quantification by DTC Genomic Companies
Condition and SNP N GECeliac disease rs2187668 (HLA-DQA1) T A GG 0.3 CC 1 CC 0.48 GG 7Colorectal & prostate cancer rs6983267 (POU5F1P1) - colorectal G G GT 0.99 GT 1.04 GG 1.16 GT 1.3 rs6983267 (POU5F1P1) - prostate G G GT 0.99 GT 1.26 GG 1.26 GT 1.4Crohn’s disease rs17234657 (PTGER4) G G TT 0.96 TT 1 TT 0.95 GG 2.3Type 2 diabetes rs1111875 (HHEX) C G GG 1.14 CC 1.2 CT 0.98 AA 1.1 rs1801282 (PPARG) C C CG 0.9 CC 1.53 CC 1.02 CC 1.1 rs4402960 (IGF2BP2) T T GG 0.92 GT 1.16 GT 1.05 GG 1.2Glaucoma rs2165241 (LOXL1) T T CC 0.03 CC 1 TT 2.94 TT 2Multiple sclerosis rs6897932 (IL7R) C C CC 1.08 CT 1.46 CC 1.08 CC 1.2Legend: D=deCODEme, N=Navigenics, 2=23andme, GE=Gene Essence
Risk Allele Genotype Example and Assigned Risk ValueD N 2 GE
Source: Swan, M. Multigenic Condition Risk Assessment in Direct-to-Consumer Genomic Services. Genet. Med. 2010, in press. http://melanieswan.com/documents/multigenic_analysis.xls
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Genomics comparison scorecard
Consumer genomic service
# Cond-itions
Cost Report Data access
Visible research quality1
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
1Conditions, genes, variants, underlying research references, and methodology white paper(s) available on public website
Which service to buy?
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Consumer resource: AccessDNA.com
Information on genetic tests from 65 companies
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DIYgenomics.org genomics comparison
PersonalGenomics Android app and web app
1. 20 conditions 2. Locus/SNP detail 3. Reference detail 4. PubMed detail
Application developed by: Michael Kolb, Lawrence S. Wong, Melanie Swan
Source: http://www.diygenomics.org
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Agenda
Consumer genomic landscape DNA sequencing technology DIYgenomics citizen science
Image credit: http://current.com/1u8qe4c
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Early sequencing technology
Sanger sequencing (chain termination) Make millions of different-length copies Print on electrophoresis gel
Read lengths small to large Fluorescent indicators denote bases
Reassemble small segments with shotgun sequencing
Sources: http://www.phgfoundation.org/tutorials/dna/5.html, http://www.genomicseducation.ca/files/images/information_articles/sequencing.gif
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Contemporary (2nd-gen) sequencing technology
Illumina Solexa, ABI SOLiD, 454 Illumina example
Attach adaptors to short sequences Amplify by growing clusters Add nucleotides, primers Activate a laser to read bases as
incorporated Assemble clusters simultaneously
Improved read time Two gigabases/day at $0.001 per
1000 bases vs. Sanger sequencing (one year at $0.10 per 1000 bases)
Hiseq (Jan 2010): 25 gigabases/day
Source: http://www.wellcome.ac.uk/News/2009/Features/WTX056032.htm
Illumina sequencing
1
2
3
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3rd-generation sequencing
Sequencing by synthesis pyrosequencing example: Pacific Biosciences SMRT (30,000-fold improvement)
Sources: http://www.pacificbiosciences.com/video_lg.html, http://www.sciencemag.org/cgi/content/abstract/323/5910/133, 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
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4th-generation sequencing technology
Electronic sequencing Ion Torrent, NABsys, Oxford
Nanopore Technologies, Agilent, Sequenom, IBM
Electron microscope reads ZS Genetics, Halcyon Molecular
George Church’s list of next-gen sequencing technologies http://arep.med.harvard.edu/Polonator
Sources: http://www.nanoporetech.com/sequences, http://www.youtube.com/watch?v=wvclP3GySUY
Oxford Nanopore Technologies
Ion Torrent
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DNA sequencing and genetic variation
Genome 3 billion base pairs
Variation #1: SNP differences (single nucleotide polymorphism) Little variation (0.1%)
Variation #2: structural Significant variation (12%) Copy-number variation Insertions Deletions Inversions
Image credit: http://im.encyklopedie.seznam.cz/wiki_cz//image/27/119427-180px-dna-snp.svg.png
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Contemporary research in genomics
Copy number variation (CNV) Cancer Pharmacogenomics Aging Microbiome Individual, family, community
medical records
Image credit: http://www.uchsc.edu/vivat/2006/September2006/images/DNA_strand.jpg
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Moore’s Law in life sciences: Carlson curves
Killer apps of DNA:
Sequencing (reading)
Synthesizing (writing)
Source: http://www.synthesis.cc/carlson_DNA_cost_curves_Sept_09.jpg
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Agenda
Consumer genomic landscape DNA sequencing technology DIYgenomics citizen science
Image credit: http://current.com/1u8qe4c
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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.; G1) Opportunity: genomic database with three minimal fields:
gene, rsid# and risk allele Current genomics search resources
PharmGKB, dbSNP, GWAS catalog, SNPedia
Source: http://www.wired.com/wiredscience/2009/10/genetically-bad-driving1Ribeiro, L. et. Al., The brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism and depression in
Mexican-Americans. Cellular, Molecular and Developmental Neuroscience. May 8, 2007.
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Finding your BDNF data, variant rs6265
Consumer genomic services genotype 600,000-1m variants but only map a few up to the annotation browser
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Consumer genomics enables peer research
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15 citizen science genomic projects http://diygenomics.pbworks.com
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Project #1: MTHFR mutation & Vit B12 deficiency http://diygenomics.pbworks.com/MTHFR
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Project #2: Longevity and genomicsBU 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. http://cancercontrol.cancer.gov/od/phg/presentations/Green.pdf
No clinical treatment currently available ε4 positive participants reported health behavior changes
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DIYbio: self-genotyping
DNA Extraction
Sources: http://www.instructables.com/id/5_minute_DNA_Extraction_in_a_Shot_Glass, http://www.boston.com/news/science/articles/2009/05/11/do_it_yourself_genetic_sleuthing, DNA 2.0 Gene Designer, https://www.dna20.com/index.php?pageID=220, http://openwetware.org/wiki/User:Jonathan_Cline/Notebook/Melaminometer
DNA Design Melaminometer
Hemochromatosis self-testKatherine Aull
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Next-generation citizen science
Exome cohort, RNA sequencing of mutations Infer copy number variation from sequence/genotype Algorithm/artificial intelligence (NLP) projects
Generate phenotypic databases (e.g.; Framingham data) Generate core SNP list by condition using algorithms Spider Pubmed for all SNPs related to conditions
‘Environmentome’ projects Cancer maps and EPA data meets web 2.0 & mobiletech Personal screening apps (environmentome & microbiome)
MicrobiomePhenotype EnvironmentGenotype
Preventive medicine health data streams
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Societal impact of genomics
Image credit: "Primo Posthuman“, Natasha Vita-More, 1997.
Good & bad sides of newtech First trimester sex determination Counsyl: hearing loss condition
“Pathologizing” new classes of conditions Discovery/cure lag
Genetic privacy: ‘the real identity theft’ GINA
Adoption/non-adoption ethics of radical enhancement technologies
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Personal genome analysis startups / tools Crossbow (UMD/College Park, MD): a scalable software pipeline
for whole genome resequencing analysis DNA Guide (Sebastopol, CA): GIS technology used to create a
personal ‘Goolge Earth map’ of the genome DNAnexus (Palo Alto, CA): web technologies on a cloud computing
infrastructure to create a compute platform for the genome era Genomera (Sunnyvale, CA): Personal genomics community
(“genomes like me”) GenoViz (SourceForge.net): Tools for genomic data visualization 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
HolGenTech (Sunnyvale, CA): Android application using genetic markers for nutrition choice, video.
SNPedia (Maryland & the Netherlands): Open-source database for genome sharing and genome interpretation via Promethease report
Portable Genomics (France): smartphone genome browser
Sources: http://openthoughtspace.pbworks.com/Personal-Genome-Analysis
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Resources
Consumer genomic resources http://diygenomics.org http://www.accessdna.com
Genomics 101 http://www.pgpstudy.org
Conferences, podcasts and video http://www.consumergeneticsshow.com http://www.phgfoundation.org/tutorials/dna
DIYbio meetup, email list, resources http://www.meetup.com/diybio http://diybio.org http://biocurious.org
Public genomic studies http://www.personalgenomes.org http://coriell.org
Image credit: http://www.rsc.org/images/DNA-scrunching-350_tcm18-68641.jpg
Thank you!
Melanie SwanResearch Fellow
MS Futures Group+1-650-681-9482
@LaBloggam@melanieswan.com
www.melanieswan.com
Slides: http://slideshare.net/LaBlogga/slideshows
Creative Commons 3.0 license
Image credit: http://www-nmr.cabm.rutgers.edu/photogallery/proteins/gif/dna.gif
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