Personal Genomes: what can I do with my data?

Revolutionizing Biology with Personal Genomes Melanie Swan Research Fellow MS Futures Group +1-650-681-9482 @LaBlogga [email_address] 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

Agenda
Consumer genomic landscape
DNA sequencing technology
DIYgenomics citizen science
DIYgenomics.org Image credit: http://current.com/1u8qe4c

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)
DIYgenomics.org 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

Direct-to-Consumer genomics landscape DIYgenomics.org $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

Example: Breast cancer – Navigenics DIYgenomics.org Source: http://www.navigenics.com/demo/for_scientists/d/breast_cancer

Example: Breast cancer – deCODEme DIYgenomics.org Source: http://demo.decodeme.com/health-watch/details/BCRS

Example: Breast cancer – 23andme DIYgenomics.org Source: https://www.23andme.com/you/journal/breastcancer/techreport

Example: Breast cancer – Pathway Genomics DIYgenomics.org Source: https://www.pathway.com

Side-by-side comparison: breast cancer
22 Variants at 15 loci are reviewed
DIYgenomics.org Source: http://www.diygenomics.org/, http://melanieswan.com/documents/multigenic_analysis.xls Markers reviewed by consumer genomic services for breast cancer

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
DIYgenomics.org 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

1. Differences in population average lifetime risk DIYgenomics.org 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

2. Differences in SNP/loci selection criteria
Less than a quarter of all loci (22%) are being reviewed by the three biggest companies
DIYgenomics.org 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

3. Differences in risk assignment methodology
Relative risk assignment per SNP
Debate: include only strong-effect markers
Composite risk assignment per condition
DIYgenomics.org 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 Risk Allele Quantification by DTC Genomic Companies

Genomics comparison scorecard DIYgenomics.org 1 Conditions, genes, variants, underlying research references, and methodology white paper(s) available on public website
Which service to buy?
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

Consumer resource: AccessDNA.com DIYgenomics.org
Information on genetic tests from 65 companies

DIYgenomics.org genomics comparison
PersonalGenomics Android app and web app
DIYgenomics.org 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

Agenda

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
DIYgenomics.org Sources: http://www.phgfoundation.org/tutorials/dna/5.html, http://www.genomicseducation.ca/files/images/information_articles/sequencing.gif

Contemporary (2 nd -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
DIYgenomics.org Source: http://www.wellcome.ac.uk/News/2009/Features/WTX056032.htm Illumina sequencing 1 2 3

3 rd -generation sequencing
Sequencing by synthesis pyrosequencing example: Pacific Biosciences SMRT (30,000-fold improvement)
DIYgenomics.org 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

4 th -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
DIYgenomics.org Sources: http://www.nanoporetech.com/sequences, http://www.youtube.com/watch?v=wvclP3GySUY Oxford Nanopore Technologies Ion Torrent

DNA sequencing and genetic variation DIYgenomics.org
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

Contemporary research in genomics DIYgenomics.org
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

Moore’s Law in life sciences: Carlson curves DIYgenomics.org
Killer apps of DNA:
Sequencing
(reading)
Synthesizing
(writing)
Source: http://www.synthesis.cc/carlson_DNA_cost_curves_Sept_09.jpg

Agenda

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
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 DIYgenomics.org
Consumer genomic services genotype 600,000-1m variants but only map a few up to the annotation browser

Consumer genomics enables peer research DIYgenomics.org

15 citizen science genomic projects http://diygenomics.pbworks.com DIYgenomics.org

Project #1: MTHFR mutation & Vit B12 deficiency http://diygenomics.pbworks.com/MTHFR DIYgenomics.org

Project #2: Longevity and genomics BU Centenarian study, Alzheimer’s disease DIYgenomics.org 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

DIYbio: self-genotyping DIYgenomics.org 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-test Katherine Aull

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)
DIYgenomics.org Microbiome Phenotype Environment Genotype Preventive medicine health data streams

Societal impact of genomics
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
DIYgenomics.org Image credit: "Primo Posthuman“, Natasha Vita-More, 1997.

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
DIYgenomics.org Sources: http://openthoughtspace.pbworks.com/Personal-Genome-Analysis

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
DIYgenomics.org Image credit: http://www.rsc.org/images/DNA-scrunching-350_tcm18-68641.jpg

Thank you! Melanie Swan Research Fellow MS Futures Group +1-650-681-9482 @LaBlogga [email_address] 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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Personal Genomes: what can I do with my data?

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