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BIO-INFO-R-MATICS 
劉佳鑫 
中研院統計科學研究所 
中研院國際研究生生物資訊學程
HI! STORY~~~C.S. 
Atanasoff-Berry 
(first electronic digital computer ) 
FORTRAN 
1939 
1954 
1955 
First disk storage (IBM) 
1963 
BASIC 
1969 
UNIX OS 
1970 
SD RAM 
1972 
C 
1981~85 
DOS, Windows, C++ 
1994 
JAVA 
2007
MAY, 1951 
Rosalind Elsie Franklin 
Photo No. 51
HI! STORY~~~BIOLOGY 
1953 
1939 
Computer 
science
HI! STORY~~~BIOLOGY 
1953 
Structure of DNA 
A = T 
C≣G 
1939 
Computer 
science
HI! STORY~~~BIOLOGY 
The theories of Heredity 
Chromosome, gene, protein 
1953 
Structure of DNA 
1944 
DNA was the agent 
responsible for transferring 
genetic information 
1822 
1884 
1943 
1859 Darwinian Evolution 
On the Origin of Species 
1890 
Sir Ronald Aylmer Fisher 
neo-Darwinian synthesis 
population genetics 
ANOVA 
The Design of Experiments 
1962 
Statistics !! 
1990 
2003 
Human Genome Project 2008 
2012 
1000 Genome Project 
1939 
Computer 
science 
Lamarckian Evolution 
1801
DATE! DATE! DATE! 
Biology Statistics Computer 
Genetics 
Evolution 
Cell biology 
Molecule biology 
Biochemistry 
Medical science 
Bioinformatics
Bioinformatics 
Biology
BIOINFOMATICIAN 
5 levels 
Level 1: Analyze data on websites …… 
Level 2: Install software and conduct it ! 
Level 3: Programming (C/R/JAVA/PERL/Paython……) 
Level 4: Write scripts of known algorithms, combine ,and maintain them 
Level 5: Develop new algorithm to solve question in biology 
1 
2 3 
4 
5
LEVEL 1 
Paste 
Submit
LEVEL 1
LEVEL 2 
Installation guide
DATA SCIENCE
Visualization 
Parsing
LEVEL 3
LEVEL 4 
seed=1234, 
sample.size=500, 
resample.number=1000, 
alpha=0.05 
original.sample<-runif(sample.size, min=0, max=1) 
resample.results<-data.frame("Run.Number"=NULL,"mean"=NULL) 
for(counter in 1:resample.number){ 
temp<-sample(original.sample, size=length(original.sample), replace = TRUE) 
temp.mean<-mean(temp) 
temp.table.row<-data.frame("Run.Number"=counter,"mean"=temp.mean) 
resample.results<-rbind(resample.results,temp.table.row) 
} 
resample.results<-resample.results[with(resample.results, order(mean)), ] 
lowerCI.row<-resample.number*alpha/2 
upplerCI.row<-resample.number*(1-(alpha/2)) 
median.row<-resample.number/2 
median<-resample.results$mean[median.row] 
lowerCI<-resample.results$mean[lowerCI.row] 
upperCI<-resample.results$mean[upplerCI.row] 
median.run<-resample.results$Run.Number[median.row] 
lowerCI.run<-resample.results$Run.Number[lowerCI.row] 
upperCI.run<-resample.results$Run.Number[upplerCI.row] 
mc.table<-data.frame("median"=NULL,"lowerCI"=NULL,"upperCI"=NULL) 
values<-data.frame(median,lowerCI,upperCI) 
runs<-as.numeric(data.frame(median.run,lowerCI.run,upperCI.run)) 
mc.table<-rbind(mc.table,values) 
mc.table<-rbind(mc.table,runs) 
Monte Carlo simulation 
Hidden Markov model 
Simulation annealing 
Bayesian analysis 
. 
. 
. 
.
LEVEL 5
周易-形上形下 
 形而上者謂之道形而下者謂之器 
 「形」: 天象地形 
 「道」: 天象地形上存在的抽象原理(Metaphysics) 
 「器」: 天地變化、陰陽交感下所生的具體事物 
 道器不相離,如有天地,太極之理
QUESTION 
lysC 
E.coli 
lysine 
glucose lysine 
lysine 
lysine 
lysine 
lysine 
lysine 
lysine 
lysine 
lysine 
lysine 
lysine 
lysine lysine
QUESTION 
 Less than 10 % of human genome with know(?) functions 
• Only 1% code for protein 
 Identify functional elements in the Human genome 
• Genetic approach 
• Evolutionary approach 
• Biochemical approach 
AIM
GENETIC 
 Rely on sequence alterations 
 To establish the biological relevance of a DNA segment
GENETIC 
 Association ~~~~ 
• Pearson 
• Spearman 
• Logistic 
 Genome-Wide Association Studies (GWAS) 
 NHGRI GWAS Catalog
GENETICS
EVOLUTIONARY 
 Comparative genomics 
 only 5% of mammalian genomes are under strong evolutionary 
constraint across multiple species (e.g., human, mouse, and dog) 
Multiple alignment technology
BIOCHEMICAL 
 Detect biochemical activity 
 Encyclopedia of DNA Elements (ENCODE) Project 
 50% of nucleotides in the human genome are readily recognizable 
as repeat elements.
ANOTHER TOPIC IN 
BIOINFORMATICS 
 The most popular bio-industry in human history
ANOTHER TOPIC IN 
BIOINFORMATICS 
 Enzyme kinetics
ANOTHER TOPIC IN 
BIOINFORMATICS 
 Metabolic control analysis 
wiki
BIOLOGICAL NETWORKS 
Metabolism network 
KEGG 
Signal transduction network 
2008, Science Signaling 
Protein 
interaction 
network 
2004, NRG, Barabasi
BIOLOGICAL NETWORKS ANALYS I S 
 Metabolic control analysis 
 Flux balance analysis 
 Sensitivity analysis 
 Network property analysis 
 Differential equation 
 Partial differential equation 
 Linear programming 
 Genetic algorithm
TAKE HOME MESSAGE 
 History 
 Components of bioinformatics 
 Levels of involving bioinformatics 
 Some topics in bioinformatics 
 Keep thinking…… 
 Google!

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Bio info-r-matics

  • 1. BIO-INFO-R-MATICS 劉佳鑫 中研院統計科學研究所 中研院國際研究生生物資訊學程
  • 2. HI! STORY~~~C.S. Atanasoff-Berry (first electronic digital computer ) FORTRAN 1939 1954 1955 First disk storage (IBM) 1963 BASIC 1969 UNIX OS 1970 SD RAM 1972 C 1981~85 DOS, Windows, C++ 1994 JAVA 2007
  • 3. MAY, 1951 Rosalind Elsie Franklin Photo No. 51
  • 4. HI! STORY~~~BIOLOGY 1953 1939 Computer science
  • 5. HI! STORY~~~BIOLOGY 1953 Structure of DNA A = T C≣G 1939 Computer science
  • 6. HI! STORY~~~BIOLOGY The theories of Heredity Chromosome, gene, protein 1953 Structure of DNA 1944 DNA was the agent responsible for transferring genetic information 1822 1884 1943 1859 Darwinian Evolution On the Origin of Species 1890 Sir Ronald Aylmer Fisher neo-Darwinian synthesis population genetics ANOVA The Design of Experiments 1962 Statistics !! 1990 2003 Human Genome Project 2008 2012 1000 Genome Project 1939 Computer science Lamarckian Evolution 1801
  • 7. DATE! DATE! DATE! Biology Statistics Computer Genetics Evolution Cell biology Molecule biology Biochemistry Medical science Bioinformatics
  • 9. BIOINFOMATICIAN 5 levels Level 1: Analyze data on websites …… Level 2: Install software and conduct it ! Level 3: Programming (C/R/JAVA/PERL/Paython……) Level 4: Write scripts of known algorithms, combine ,and maintain them Level 5: Develop new algorithm to solve question in biology 1 2 3 4 5
  • 10. LEVEL 1 Paste Submit
  • 14.
  • 17. LEVEL 4 seed=1234, sample.size=500, resample.number=1000, alpha=0.05 original.sample<-runif(sample.size, min=0, max=1) resample.results<-data.frame("Run.Number"=NULL,"mean"=NULL) for(counter in 1:resample.number){ temp<-sample(original.sample, size=length(original.sample), replace = TRUE) temp.mean<-mean(temp) temp.table.row<-data.frame("Run.Number"=counter,"mean"=temp.mean) resample.results<-rbind(resample.results,temp.table.row) } resample.results<-resample.results[with(resample.results, order(mean)), ] lowerCI.row<-resample.number*alpha/2 upplerCI.row<-resample.number*(1-(alpha/2)) median.row<-resample.number/2 median<-resample.results$mean[median.row] lowerCI<-resample.results$mean[lowerCI.row] upperCI<-resample.results$mean[upplerCI.row] median.run<-resample.results$Run.Number[median.row] lowerCI.run<-resample.results$Run.Number[lowerCI.row] upperCI.run<-resample.results$Run.Number[upplerCI.row] mc.table<-data.frame("median"=NULL,"lowerCI"=NULL,"upperCI"=NULL) values<-data.frame(median,lowerCI,upperCI) runs<-as.numeric(data.frame(median.run,lowerCI.run,upperCI.run)) mc.table<-rbind(mc.table,values) mc.table<-rbind(mc.table,runs) Monte Carlo simulation Hidden Markov model Simulation annealing Bayesian analysis . . . .
  • 19. 周易-形上形下  形而上者謂之道形而下者謂之器  「形」: 天象地形  「道」: 天象地形上存在的抽象原理(Metaphysics)  「器」: 天地變化、陰陽交感下所生的具體事物  道器不相離,如有天地,太極之理
  • 20. QUESTION lysC E.coli lysine glucose lysine lysine lysine lysine lysine lysine lysine lysine lysine lysine lysine lysine lysine
  • 21. QUESTION  Less than 10 % of human genome with know(?) functions • Only 1% code for protein  Identify functional elements in the Human genome • Genetic approach • Evolutionary approach • Biochemical approach AIM
  • 22. GENETIC  Rely on sequence alterations  To establish the biological relevance of a DNA segment
  • 23. GENETIC  Association ~~~~ • Pearson • Spearman • Logistic  Genome-Wide Association Studies (GWAS)  NHGRI GWAS Catalog
  • 25. EVOLUTIONARY  Comparative genomics  only 5% of mammalian genomes are under strong evolutionary constraint across multiple species (e.g., human, mouse, and dog) Multiple alignment technology
  • 26. BIOCHEMICAL  Detect biochemical activity  Encyclopedia of DNA Elements (ENCODE) Project  50% of nucleotides in the human genome are readily recognizable as repeat elements.
  • 27. ANOTHER TOPIC IN BIOINFORMATICS  The most popular bio-industry in human history
  • 28. ANOTHER TOPIC IN BIOINFORMATICS  Enzyme kinetics
  • 29. ANOTHER TOPIC IN BIOINFORMATICS  Metabolic control analysis wiki
  • 30. BIOLOGICAL NETWORKS Metabolism network KEGG Signal transduction network 2008, Science Signaling Protein interaction network 2004, NRG, Barabasi
  • 31. BIOLOGICAL NETWORKS ANALYS I S  Metabolic control analysis  Flux balance analysis  Sensitivity analysis  Network property analysis  Differential equation  Partial differential equation  Linear programming  Genetic algorithm
  • 32. TAKE HOME MESSAGE  History  Components of bioinformatics  Levels of involving bioinformatics  Some topics in bioinformatics  Keep thinking……  Google!