2. Contents
1. Introduction
2. Human Genome Project and Beyond
3. Genome Data
① Cancer Targeted Therapy
② Disease Risk (Common, Rare)
③ Pharmacogenomics
④ Others (Fetal DNA, Microbiome)
4. Sensor/Mobile Data
5. Electrical Health Records
6. National Healthcare Data
7. Medical Images
8. Biomedical Big Data + Artificial Intelligence
3. Contents
1. Introduction
2. Human Genome Project and Beyond
3. Genome Data
① Cancer Targeted Therapy
② Disease Risk (Common, Rare)
③ Pharmacogenomics
④ Others (Fetal DNA, Microbiome)
4. Sensor/Mobile Data
5. Electrical Health Records
6. National Healthcare Data
7. Medical Images
8. Biomedical Big Data + Artificial Intelligence
10. 며칠 전 유전자 검사를 받은 40대 남성입니다.
혈액세포의 DNA 상태를 분석해 앞으로 암에 걸릴 위험이 있는지 여부를 판단할 수 있다
고 합니다.
2013.4.25. KBS 9시 뉴스
11. 2013.4.25. KBS 9시 뉴스
60년전 DNA의 구조가 밝혀진 이래 2003년 인간 유전자 지도가 완성됐고, 현재는 어떤 유
전자가 어떤 질병을 일으키는지 분석도 80% 정도 끝난 상태입니다.
예를들어 13번 염색체의 BRCA2 유전자에 이상이 생기면 유방암에 걸릴 확률이 높습니
다. 또 17번 염색체 유전자는 난소암, 7번 염색체 유전자는 비만을 일으킵니다.
15. Contents
1. Introduction
2. Human Genome Project and Beyond
3. Genome Data
① Cancer Targeted Therapy
② Disease Risk (Common, Rare)
③ Pharmacogenomics
④ Others (Fetal DNA, Microbiome)
4. Sensor/Mobile Data
5. Electrical Health Records
6. National Healthcare Data
7. Medical Images
8. Biomedical Big Data + Artificial Intelligence
17. Tissue Specific Expression
Comprehensive Catalogues of Genomic Data
Variation in the human genome
Mendelian (monogenic) diseases
(N=22,432)
Whole genome sequencing (N=1,000)
Four ethnic groups
(CEU, YRI, JPT, CHB, N=270)
GWAS catalog
Complex (multigenic) traits
(1926 publications and 13410 SNPs)
Disease-related variations
Functional elements
2014-06-29
17
18. All Major Tissues/Organs
All Proteins + All RNAs
2015 Science Tissue-based map of the human proteome
1. Immunohistochemistry (IHC)
24,028 antibodies
(16,975 proteins)
>13 million IHC images
2. RNA-sequencing
(N=44)
18
19. 111 Reference Human Epigenomes
2015.2.19. Nature. Integrative analysis of 111 reference human epigenomes19
29. 1000 개의 질병들
Bioinformatics. 2010 PheWAS: demonstrating the feasibility of a phenome-wide scan to discover gene-disease associations.
Phenotype-wide Association Study
32. Contents
1. Introduction
2. Human Genome Project and Beyond
3. Genome Data
① Cancer Targeted Therapy
② Disease Risk (Common, Rare)
③ Pharmacogenomics
④ Others (Fetal DNA, Microbiome)
4. Sensor/Mobile Data
5. Electrical Health Records
6. National Healthcare Data
7. Medical Images
8. Biomedical Big Data + Artificial Intelligence
35. Disease genetic susceptibility
Cancer driver
somatic mutation
Pharmacogenomics
Targeted
Cancer Treatment
(EGFR)
Causal
Variant
Targeted Drug
(MODY-SU)
Drug Efficacy/Side Effect
Related Genotype
(CYP, HLA)
Genetic Diagnosis
(Mendelian,
Cystic fibrosis)
Molecular
Classification
- Prognosis
(Leukemia)
Hereditary
Cancer
(BRCA)
Microbiome
(Bacteria,
Virus)
Genomic Medicine
Risk prediction
(Complex disease,
Diabetes)
Germline Variants
Fetal DNA
36. Contents
1. Introduction
2. Human Genome Project and Beyond
3. Genome Data
① Cancer Targeted Therapy
② Disease Risk (Common, Rare)
③ Pharmacogenomics
④ Others (Fetal DNA, Microbiome)
4. Sensor/Mobile Data
5. Electrical Health Records
6. National Healthcare Data
7. Medical Images
8. Biomedical Big Data + Artificial Intelligence
41. Contents
1. Introduction
2. Human Genome Project and Beyond
3. Genome Data
① Cancer Targeted Therapy
② Disease Risk (Common, Rare)
③ Pharmacogenomics
④ Others (Fetal DNA, Microbiome)
4. Sensor/Mobile Data
5. Electrical Health Records
6. National Healthcare Data
7. Medical Images
8. Biomedical Big Data + Artificial Intelligence
46. Tissue Specific Gene Expression
2015 Nature Genetic studies of body mass index yield new insights for obesity biology
- Hypothalamus, Pituitary gland
(appetite regulation)
- Hippocampus, Limbic system
(learning, cognition, emotion,
memory)
47. Gene Set Enrichment Analysis
2015 Nature Genetic studies of body mass index yield new insights for obesity biology
48. Per-allele effect of BMI-associated
loci on body weight
2012 Genetic determinants of common obesity and their value in prediction
49. 2011 Hum Genet. Type 2 diabetes and obesity- genomics and the clinic
50. 2015 Nature Genetic studies of
body mass index yield new
insights for obesity biology
Blue: Previous
Red: Novel
51. 2011 Hum Genet. Type 2 diabetes and obesity- genomics and the clinic
TCF7L2
52. ◇◆ ‘parental obesity’
as a test to predict obesity
in adult life
•Dark blue 1–2 yrs
•Green 3–5 yrs
•Red 6–9 yrs
•Light blue 10–14 yrs
•Grey , 15–17 yrs
Genetic Prediction of Obesity Risk
The predictive ability of
the currently
established BMI-
associated loci is poor
2012 Genetic determinants of common obesity and their value in prediction
53. Influence of Genetics on Human Disease
For any condition the overall balance of g
enetic and environmental determinants ca
n be represented by a point somewhere w
ithin the triangle.
53
Single
Locus /
Mendelian
Multiple
Loci or multi-
chromosomal
Environmental
Cystic Fibrosis
Hemophilia A
Examples:
Alzheimer’s Disease
Type II Diabetes
Cardiovascular Disease
Diet
Carcinogens
Infections
Stress
Radiation
Lifestyle
Gene = F8
Gene= CFTR
F8 = Coagulation Factor VIII
CFTR = Cystic Fibrosis Conductance Transmembrane Regulator
Lung Cancer
57. Diabetes ≠ Genetic Disease?
• Familial aggregation
– Genetic influences?
– Epigenetic influences
• Intrauterine environment
– Shared family environment?
• Socioeconomic status
• Dietary preferences
• Food availability
• Gut microbiome content
• Overestimated heritability
– Phantom heritability
2012. Drong AW, Lindgren CM, McCarthy MI. Clin Pharmacol Ther. The genetic and epigenetic basis of type 2 diabetes and obesity.
2012. PNAS The mystery of missing heritability- Genetic interactions create phantom heritability57
58. Rare Variant in a Specific Population
• 3756 Latino: whole exome sequencing
A rare functional variant in candidate gene
14276: replication Not found in other ethnic group
2014 JAMA Association of a Low-Frequency Variant in HNF1A With Type 2 Diabetes in a Latino Population
59. 2014 NEJM Null Mutation in Hormone-Sensitive Lipase Gene and Risk of Type 2 Diabetes
Rare Functional Variant
= Monogenic Heritable Disease
All Amish
60. Variants and Disease Susceptibility
2008 NRG Genome-wide association studies for complex traits- consensus, uncertainty and challenges
61.
62. Genotype Based Diabetes Therapy
Diabetes due to KATP channel mutations sulphonylurea
2007 American Journal of Physiology - Endocrinology and Metabolism. ATP-sensitive K+ channels and disease- from molecule to malady
67. Contents
1. Introduction
2. Human Genome Project and Beyond
3. Genome Data
① Cancer Targeted Therapy
② Disease Risk (Common, Rare)
③ Pharmacogenomics
④ Others (Fetal DNA, Microbiome)
4. Sensor/Mobile Data
5. Electrical Health Records
6. National Healthcare Data
7. Medical Images
8. Biomedical Big Data + Artificial Intelligence
68. 2012 European Heart Journal. Personalized medicine: hope or hype?
Herceptin
Glivec
68
69. 69
Pharmacogenomic Biomarkers
in Drug Labeling (N=166)
2015.9.14.
Atorvastatin, Azathioprine,
Carbamazepine, Carvediolol,
Clopidogrel, Codein,
Diazepam…..
70. Large Effect Size Variant?
Disease susceptibility variant Pharmacogenetic variant
Environmental
Exposure
Drug
Exposure
83. Personalized Medicine
Pharmacogenomics
Nutrigenomics
IRS1 SNP GA/AA
High fat/
Low carb
IRS1 SNP GG
Standard
Higher
effect
Similar
effect
2013 Diabetes Care. IRS1 Genotype Modulates Metabolic Syndrome Reversion in Response to 2-Year Weight-Loss Diet Intervention - The POUNDS LOST trial
86. Genotype Guided Personalized Treatment
Baseline
Genotyping
- Drug metabolism
- DM etiology
- DM complication
1 week 3 month Long term
Genotype based treatment strategy
- Drug choice
- Drug dose
- Lifestyle modification
- Complication evaluation
New
T2DM
87. Pharmacogenetic Tests: 최형진
No
Drug
(N= 10)
Gene
(6 genes=8 bioma
rkers)
Target SNPs
(N=12)
#5
(HJC)
Genotype Interpretation Clinical Interpretation
1 Clopidogrel CYP2C19
rs4244285 (G>A) GG
*1/*1
(EM)
Use standard dosers4986893 (G>A) GG
rs12248560 (C>T) CC
2 Warfarin
VKORC1 rs9923231 (C>T) TT
Low dose
(higher risk of bleeding)
Warfarin dose=0.5~2 mg/day
CYP2C9
rs1799853 (C>T) CC
rs1057910 (A>C) AC
3 Simvastatin SLCO1B1 rs4149056 (T>C) TT Normal
4
Azathioprine (AP),
MP, or TG
TPMT rs1142345 (A>G) AA Normal
5
Carbamazepine
or Phenytoin
HLA-B*1502
rs2844682 (C>T) CT
Normal
rs3909184 (C>G) CC
6 Abacavir HLA-B*5701 rs2395029 (T>G) TT Normal
7 Allopurinol HLA-B*5801 rs9263726 (G>A) GG Normal
Clopidogrel1)
: UM/EM=standard dose, IM/PM= consider alternative antiplatelet agent (eg. prasugrel/ticagrelor)
Warfarin2)
: high dose=5~7 mg/day, medium dose=3~4 mg/day, low dose=0.5~2 mg/day
=0
최형진
+1,000,000
?
88. Contents
1. Introduction
2. Human Genome Project and Beyond
3. Genome Data
① Cancer Targeted Therapy
② Disease Risk (Common, Rare)
③ Pharmacogenomics
④ Others (Fetal DNA, Microbiome)
4. Sensor/Mobile Data
5. Electrical Health Records
6. National Healthcare Data
7. Medical Images
8. Biomedical Big Data + Artificial Intelligence
96. Future of Genomic Medicine?
Test when neededWithout information Know your type
Blood
type
Geno
type
Here is my
sequence
97. Contents
1. Introduction
2. Human Genome Project and Beyond
3. Genome Data
① Cancer Targeted Therapy
② Disease Risk (Common, Rare)
③ Pharmacogenomics
④ Others (Fetal DNA, Microbiome)
4. Sensor/Mobile Data
5. Electrical Health Records
6. National Healthcare Data
7. Medical Images
8. Biomedical Big Data + Artificial Intelligence
121. 121 2015 Cell Metabolism. A Smartphone App Reveals Erratic Diurnal Eating Patterns in Humans that Can Be Modulated for Health Benefits
November 3, 2015
122. 122 2015 Cell Metabolism. A Smartphone App Reveals Erratic Diurnal Eating Patterns in Humans that Can Be Modulated for Health Benefits
123. Personalized Nutrition by
Prediction of Glycemic Responses
123
2015 Cell. Personalized Nutrition by Prediction of Glycemic Responses
Received: October 5, 2015;
Received in revised form:
October 29, 2015;
Accepted: October 30, 2015;
127. Contents
1. Introduction
2. Human Genome Project and Beyond
3. Genome Data
① Cancer Targeted Therapy
② Disease Risk (Common, Rare)
③ Pharmacogenomics
④ Others (Fetal DNA, Microbiome)
4. Sensor/Mobile Data
5. Electrical Health Records
6. National Healthcare Data
7. Medical Images
8. Biomedical Big Data + Artificial Intelligence
128. Electronic Health Records
2012 NRG Mining electronic health records- towards better research applications and clinical care
128
132. 밤동안 저혈당수면 Lt.foot rolling Keep떨림,
식은땀, 현기증, 공복감, 두통, 피로감등의 저혈
당 에 저혈당 이 있을 즉알려주도록 밤사이 특
이호소 수면유지상처와 통증 상처부위 출혈
oozing, severe pain 알리도록 고혈당 처방된 당
뇨식이의 중요성과 간식을 자제하도록 .고혈
당 ,,관리 방법 .당뇨약 이해 잘 하고 수술부위
oozing Rt.foot rolling keep드레싱 상태를 고혈
당 고혈당 의식변화 BST 387 checked.고혈당
으로 인한 구강 내 감염 위해 식후 양치, gargle
등 구강 위생 격려.당뇨환자의 발관리 방법에 .
목표 혈당, 목표 당화혈색소에 .식사를 거르거
나 지연하지 않도록 .식사요법, 운동요법, 약물
요법을 정확히 지키는 것이 중요을 .처방된 당
뇨식이의 중요성과 간식을 자제하도록 .고혈
당 ,,관리 방법 .혈당 정상 범위임rt foot rolling
중으로 pain호소 밤사이 수면양호걱정신경 예
민감정변화 중임감정을 표현하도록 지지하고
경청기분상태 condition 조금 나은 듯 하다고 혈
당 조절과 관련하여 신경쓰는 모습 보이며 혈당
self로 측정하는 모습 보임혈당 조절에 안내하
고 불편감 지속알리도록고혈당 고혈당 의식변
화 고혈당 허약감 지남력 혈당조절 안됨고혈당
으로 인한 구강 내 감염 위해 식후 양치, gargle
등 구강 위생 격려.당뇨환자의 정기점검 내용과
빈도에 .BST 140 으로 저혈당 호소 밤동안 저
혈당수면 Lt.foot rolling Keep떨림, 식은땀, 현
기증, 공복감, 두통, 피로감등의 저혈당 에 저
혈당 이 있을 즉알려주도록 pain 및 불편감 호
소 WA 잘고혈당 고혈당 의식변화 고혈당 허
약감 지남력 혈당조절 안됨식사요법, 운동요법,
약물요법을 정확히 지키는 것이 중요을 .저혈당
/고혈당 과 대처법에 .혈당정상화, 표준체중의
유지, 정상 혈중지질의 유지에 .고혈당 ,,관리
방법 .혈당측정법,인슐린 자가 투여법, 경구투
약,수분 섭취량,대체 탄수화물,의료진의 도움이
필요한 사항에 교혈당 정상 범위임수술부위
oozing Rt.foot rolling keep수술 부위 (출혈, 통
증, 부종)수술부위 출혈 상처부위 oozing
Wound 당겨지지 않도록 적절한 체위 취하기
설명감염 발생 위험 요인 수술부위 출혈 밤동안
간호기록지 Word Cloud
Natural Language Processing (NLP)132
133. Contents
1. Introduction
2. Human Genome Project and Beyond
3. Genome Data
① Cancer Targeted Therapy
② Disease Risk (Common, Rare)
③ Pharmacogenomics
④ Others (Fetal DNA, Microbiome)
4. Sensor/Mobile Data
5. Electrical Health Records
6. National Healthcare Data
7. Medical Images
8. Biomedical Big Data + Artificial Intelligence
138. Korean Society for
Bone and Mineral
Research
Anti-hypertensive
prescriptions
(2008-2011)
N = 8,315,709
New users
N = 2,357,908
Age ≥ 50 yrs
Monotherapy
Compliant user (MPR≥80%)
No previous fracture
N = 528,522
Prevalent users
N = 5,957,801
Excluded
Age <50
Combination therapy
Inadequate compliance
Previous fracture
N = 1,829,386
Final study population
심평원 빅데이터 연구
고혈압약과 골절
Choi et al., 2015 International Journal of Cardiology138
139. Compare Fracture Risk
Comparator?Hypertension
CCB
High
Blood Pressure
Fracture
Risk
BB
Non-
user
Healthy
Non-
user
Cohort study (Health Insurance Review & Assessment Service)
New-user design (drug-related toxicity)
Non-user comparator (hypertension without medication)
2007 20112008
Choi et al., 2015 International Journal of Cardiology139
141. Contents
1. Introduction
2. Human Genome Project and Beyond
3. Genome Data
① Cancer Targeted Therapy
② Disease Risk (Common, Rare)
③ Pharmacogenomics
④ Others (Fetal DNA, Microbiome)
4. Sensor/Mobile Data
5. Electrical Health Records
6. National Healthcare Data
7. Medical Images
8. Biomedical Big Data + Artificial Intelligence
147. 147
2013 Science Functional interactions as big data in the human brain
2012 Decoding subject-driven cognitive states with whole-brain connectivity patterns
149. Quantitative nuclear morphometry
2015 Laboratory Investigation. Novel genotype-phenotype associations in human cancers enabled by advanced molecular platforms and computational analysis
of whole slide images
150. Contents
1. Introduction
2. Human Genome Project and Beyond
3. Genome Data
① Cancer Targeted Therapy
② Disease Risk (Common, Rare)
③ Pharmacogenomics
④ Others (Fetal DNA, Microbiome)
4. Sensor/Mobile Data
5. Electrical Health Records
6. National Healthcare Data
7. Medical Images
8. Biomedical Big Data + Artificial Intelligence
157. 157
In a scan of 3,000 images, IBM
technology was able to spot
melanoma with an accuracy
of about 95 percent, much
better than the 75 percent to
84 percent average of today's
largely manual methods.
IBM Research will continue to
work with Sloan Kettering to
develop additional
measurements and
approaches to further refine
diagnosis, as well as refine
their approach through larger
sets of data.
Dec 17, 2014
158. 158
Aug. 11, 2015
IBM is betting that the same technology that
recognizes cats can identify tumors and other signs of
diseases.
In the long run, IBM and others in the field hope such
systems can become reliable advisers to
radiologists, dermatologists and other practitioners
who analyze images—especially in parts of the world
where health-care providers are scarce.
While IBM hopes Watson will learn to interpret
Merge’s images, it also expects the combination of
imagery, medical records and other data to reveal
patterns relevant to diagnosis and treatment that a
human physician may miss, ushering in an era of
computer-assisted care. Two other recent IBM
acquisitions, Phytel Inc. and Explorys Inc., yielded 50
million electronic medical records.
Current results are not sufficient to isolate specific brain regions important
in regulating BMI. However, we observe enrichment not only in
the hypothalamus and pituitary gland—key sites of central appetite
regulation—but even more strongly in the hippocampus and limbic system,
tissues that have a role in learning, cognition, emotion and memory.
The strongest enrichment was observed with promoter (histone 3
Lys 4 trimethylation (H3K4me3), histone 3 Lys 9 acetylation (H3K9ac))
and enhancer (H3K4me1, HeK27ac) marks detected in mid-frontal
lobe, anterior caudate, astrocytes and substantia nigra, supporting neuronal
tissues in BMI regulation.
synaptic function, long-term potentiation and neurotransmitter
signalling (glutamate signalling in particular, but also noradrenaline,
dopamine and serotonin release cycles, and GABA (c-aminobutyric acid)
receptor activity
"mid-frontal lobe, anterior caudate, astrocytes and substantia nigra, supporting neuronal tissues in BMI regulation"
"provides the strongest genetic evidence so far for a role of particular
biological and CNS processes in the regulation of human body mass."
Extreme Phenotype Group in Amish (high TG, N=24)
Sequencing- Candidate Gene Approach (lipid pathway 24 genes)
One subject – deletion detected
Genotyping in 2738 Amish
140 heterozygoe, 1 homozygote
5.1% of Amish persons carry the D allele, as compared with 0.2% of non-Amish persons of European descent