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Genomics Dual Factors for Physical Life◦ Genetic factors for systems healthcare◦ Acquired factors for systems healthcare

Opportunities and Challenges

Anatomy Microscope/Cell Biology Molecular Biology

Bioinformatics and Systems Biology

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Personal Physical Life = f (Nature, Nurture)Nature: Genes – Personal Genome Project

Nurture: Environment, Food, Exercise, Medication, …

Data Collection Data Mining Understanding/Prediction

G1 G2 … … Gp E1 E2 … … Eq L1 L2 … … Lr

P1

……Pm

Feature SelectionModel-Based Data MiningNew Approaches ?

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1 SNP in every 2kb of genomic sequences Synonymous vs. non-synonymous SNP

1….ATCCTGTACCTACGTGTACAATAGTA…..CTGATCATCTCTATGGG….2….ATCCTGTTCCTACGTGTACAATAGTA….. CTGATCATCTCTATGGG….3….ATCCTGTACCTACGTGTACAATAGTA…..CTGATCAGCTCTATGGG….

1 2 3

SNP1 SNP2

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1G: Sanger

2G: Parallel

3G: Single Molecule

4G: Non-optical

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Human Genome Project Consortium◦ 1990 ~ 2005 (16 years), US$ 3 billion (3조원)◦ Haploid from many anonymous donors (cf. RP11, a male from Buffalo, NY)

Celera Genomics◦ 1998 ~ 2005 (8 yrs), US$ 300 million (3천억원)◦ Consensus from five anonymous donors (including Craig Ventor)

2007: Market, US$ 20 million (2백억원) 2007: Knome, US$ 350,000 (3억5천만원) for diploid sequencing 2009: US$ 100,000 (1억원) – NIH RFP Objective 2011: US$ 20,000 (2천만원) – George Church’s prediction 2014: US$ 1,000 (1백만원) – NIH RFP Objective

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6,099 GWAS studies as of Sep. 6, 201114

Pharmacogenomics

DNA(SNP) chip

Cf. HER2 Overexpress, Herceptin, Genentech, 199815

Disease risk assessment for 119 diseases◦ Clinical Reports (33) BRCA Cancer Mutations, Celiac Disease (소아지방변증) Diabetes, Parkinson’s Disease, Prostate Cancer, Rheumatoid Arthritis,

Resistance to HIV/AIDS, and so on◦ Research Reports (86) Asthma, Baldness, Bipolar Disorder, Breast Cancer, Food Preference,

Height, Longevity, Memory, Obesity … Ancestry tracking => New International Social networks?◦ Maternal line with mitochondrial DNA◦ Paternal line with Y chromosome

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Interleukin Genetics, Inc. & Amway Global Cost: US$ 100~200 / per kit1. Kit-based sampling from oral cavity2. SBE(Single Base Extension)-based detection of

SNP markers3. Bioinformatics analysis for SNP-to-trait mapping4. Recommendation for nutrition, exercise, and

medication

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Genomic sequences from whole genome parallel sequencing

Image from the sequencing machines (usually discarded after processing)

Raw sequence reads: ~300GB Genome-mapped sequences: ~300GB Binary compressed sequences: ~150GB Intermediate results: ~300GB Over 1TB/sample 1000 Genome => 1PB

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(3 x 109) bp x 30 rd x 3 = ~ 3 x 1011 bytes = ~ 300GB

@HWI-ST621:206:B0202ACXX:1:1101:1216:2021 1:Y:0:ATCACG TitleNTTTANNNNTGAATNNTGTCAAAATTACAGAAGAACTGCAAGAATATCACATGGTACACTCATACAATCTCCACCCANANNNNNNNNNNNNNNNNNTTTGC Base+ Comment##################################################################################################### Base quality@HWI-ST621:206:B0202ACXX:1:1101:1116:2024 1:Y:0:ATCACGNCTTNNNNNCACAGNNTTTAACCTTTCTTTTCTTAGAGCACTTTAGAAACACTCTGCTTGTTATGTCTGCAAGTGGANANNNNNNNNNNNNNNNNNCCTTC+#####################################################################################################

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HWI-ST621:206:B0202ACXX:1:1101:1128:2173 147 chr1 81092578 60 101M = 81092212 -467 AGGGCAGAATACCGTATCCTTGGAAAATTAAATAGTAAGAGGAGAGAGGCTTCAGTGGCAGACCATTCGGAAAGTGTGGGGAAATCCAGGAAGGAAAGTAN ##################################################################################################### XT:A:U NM:i:1 SM:i:37 AM:i:37 X0:i:1 X1:i:0 XM:i:1 XO:i:0 XG:i:0 MD:Z:100G0HWI-ST621:206:B0202ACXX:1:1101:1022:2177 73 chr3 110819717 37 101M = 110819717 0 NTCCNTTTTCATGCTGCTGATAAAGACATAGCTGAGACTGGGTAATTAAAAAAAAAAGCGGTTTAATGAACTCACAGTTTCACATGGCTGGGGGGGGCTCA ##################################################################################################### XT:A:U NM:i:4 SM:i:37 AM:i:0 X0:i:1 X1:i:0 XM:i:4 XO:i:0 XG:i:0 MD:Z:0G3A88A2C4

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Clockwork Business Solutions ©

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EDI (Electronic Data Interchange) OCS (Order Communication System) LIS (Laboratory Information System) PACS (Picture Archiving and Communication System) PIS (Pharmacy Information System) CIS (Clinical Information System) EMR (Electronic Medical Records) PHR (Personal Health Records) Etc…

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Molecular snapshots◦ Transcriptomics◦ Proteomics◦ Metabolomics

Electronics Medical Records PACS images Life log Etc…

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Gene1 Gene2 Gene3 Gene4Genome

Transcriptome mRNA1mRNA1mRNA1mRNA1mRNA1mRNA1mRNA1mRNA1mRNA1

mRNA1mRNA1mRNA2mRNA1mRNA1mRNA1mRNA1mRNA1mRNA1mRNA4

Proteome mRNA1Protein1 mRNA1mRNA1mRNA1mRNA1mRNA1mRNA1Protein4

mRNA1mRNA1mRNA1mRNA1mRNA1Protein2’

Transcriptional Regulation

Translational Regulation, Post-translational modification

mRNA1mRNA1mRNA1mRNA1mRNA1mRNA1mRNA1mRNA1Protein2

Metabolome

Metabolic Regulation

Metabolite-A Metabolite-B Metabolite-C

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A large number of structured tables with text-based fields Different schema for different organizations, cf. HL7 Security and privacy is extremely critical

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High resolution images with structured meta data

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Body composition analyzerTask: Body balance inspection Application: Wellness & fitness programCost: $ 2K

SNP genotypingTask: Individual genetic variation detection in single nucleotide polymorphismApplication: Disease prognosisCost: $ 5K

Expression profiling chipTask: Individual genomic response inspection Application:Disease prognosis (e.g. caner)Cost: $ 10K

Diabetes phoneTask:Measurement of glucose levelApplication: Diabetes, dietary managementCost: $ 400

Genomic profile

Physiologicalsignal

CNV genotypingTask: Individual genetic variation detection at copy number variationApplication: Disease prognosisCost: $ 1M

Healthcare bidetTask: Examination of user’s secretionApplication: Patient monitoring systemCost: $ 400

Diabetes watchTask: Measurement of glucose levelApplication: Diabetes, dietary managementCost: $ 100

PCR-based genetic diagnosisTask: Detection of genetic disease and predisposition to a diseaseApplication: Disease prognosisCost: $ 10K

Life shirtTask: Monitor vital signals (respiration flow, heart rate, sweat) Application:Patient monitoring systemCost: $ 2K

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Yahoo

Google

Overture => Yahoo

Amazon

Auction

Nexon

Blizzard

YouTube

Facebook

Much more …

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Medical History Health Information

Comprehensive at-home DNA test

NavigenicsNavigenicsRevealing genetic predisposition

Managing health information

Healthcare software solutions

Making personal genetics

23 and me23 and me

Helix HealthHelix Health

deCODEmedeCODEme

Scanning Traits & Disease Tracing Ancestry Features

Microsoft Health VaultMicrosoft Health Vault

Patient ManagementPersonalized Prevention Family History

Complete Scan Cardio Scan Cancer Scan

Nursing Home Application

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Data Acquisition Data Mining Information DeliveryPersonal Genomes

- Cheap Sequencing- Accurate Annotation

Personal Life Logging- EMR- Food, Exercise, ..

ULDB- Cloud computing

ULDM- Extreme bias on SV ratio- Dynamic and noisy- Incremental

Biomedical Information Models- Ultra-scale- Multi-level- Multi-precision- Multi-modality

Mobile interactionRecommendationPoint-on-treatments…

Scientific Aspects

Industrial AspectsCreative Business Models

(1) Utilizing existing resources(2) Timely join to new emerging markets(3) Accumulating intellectual properties

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