introduction to bioinformatics. 2 human genome project genome health implications a new disease...

Introduction to BioinformaticsIntroduction to Bioinformatics

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Human Genome ProjectHuman Genome Project

Genome Health Implications

A New

Disease

Encyclopedia

New Genetic

Fingerprints

New

Diagnostics

New

Treatments

Goals• Identify the approximate 40,000 genes in human DNA• Determine the sequences of the 3 billion bases that make up human DNA• Store this information in database• Develop tools for data analysis• Address the ethical, legal and social issues that arise from genome research

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BTBTITIT

Bioinformatics

Biocomputing

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What is Bioinformatics?What is Bioinformatics?

Informatics – computer science

Bio – molecular biology

Bioinformatics – solving problems arising from biology using methodology from computer science.

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Basics in Molecular BiologyBasics in Molecular Biology

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ChromosomesChromosomes

DNA in a human cell: 2m DNA in a human body: Earth-to-Sun:

km 102 11

km 105.1 8

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DNA(Deoxyribonucleic Acid)DNA(Deoxyribonucleic Acid)

Nucleotide 들로 구성 Nucleotide = Sugar + Phosphate + Nitrogenous base Adenine – Thymine Guanine – Cytosine

Double Helix 구조

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DNA Base-pairsDNA Base-pairs

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DNADNA

AACCTGCGGAAGGATCATTACCGAGTGCGGGTCCTTTGGGCCCAACCTCCCATCCGTGTCTATTGTACCCGTTGCTTCGGCGGGCCCGCCGCTTGTCGGCCGCCGGGGGGGCGCCTCTGCCCCCCGGGCCCGTGCCCGCCGGAGACCCCAACACGAACACTGTCTGAAAGCGTGCAGTCTGAGTTGATTGAATGCAATCAGTTAAAACTTTCAACAATGGATCTCTTGGTTCCGGCATGCAATCAGTCCCGTTGCTTCGGCACTGTCTGAAAGCGCCTTTGGGCCCAACCTCCCATCCGTGTCTATTGTACCCGTTGCTTCGGCGGGCCCGCCGCTTGTCGGCCGCCGGGGGGGCGCCGTTGCTTCGGCGGGCCCGCCGCTTGTCGGCCGCCGGGGCTATTGTACCCGTTGCTTCGGATCTCTTGGGGATCTCTTGGTTCCGGCATGCAATCAGTCCCGTTGCTTCGGCACTGTCTGAAAGCGCCTTTGGGCCCAACCTCCCACCGTTGCTTCGGCGGGCCCGCCGCTTGTCGGCCGCCGGGGGGGCGGCCGCCGGGGGCACTGTCTGAAAGCTCGGCCGCC

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Some FactsSome Facts

DNA differs between humans by 0.2%, (1 in 500 bases).

Human DNA is 98% identical to that of chimpanzees.

97% of DNA in the human genome has no known function.

3.2*109 letters in the DNA code in every cell in your body.

1014 cells in the body. 12,000 letters of DNA decoded by the Human

Genome Project every second.

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Gene and GenomeGene and Genome

Gene Fundamental unit of heredity 단백질을 합성하는데 필요한 정보 포함 Genome 의 일부

Genome 생명체가 갖는 전체 DNA

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Numbers of GenesNumbers of Genes

Humans 25,000 - 40,000

C. elegans (worm): 19,000

S. cerevisiae (yeast) 6,000

Tuberculosis microbe 4,000

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RNA(Ribonucleic Acid)RNA(Ribonucleic Acid)

A, C, G, U(Uracil) mRNA

DNA 에서 gene 을 transcription 하여 세포 내에서 단백질을 합성하는 기관인 ribosome 에 정보 전달

tRNA Ribosome 이 아미노산을 만들 때 , mRNA 와 아미노산 사이의 adaptor 역할을 함

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Molecular Biology: Flow of Molecular Biology: Flow of Information (Central Dogma)Information (Central Dogma)

DNA “gene”

RNA

Protein

FoldedProtein

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DNA (gene) RNA ProteinDNA (gene) RNA Protein

controlstatement

TATA start

Termination stop

controlstatement

Ribosomebinding

gene

Transcription (RNA polymerase)

mRNA

Protein

Translation (Ribosome)

5’ utr 3’ utr

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CodonCodon

tRNA 는 3 개의 nucleic acid 와 결합 codon

조합 개수 64 20 가지의 아미노산 , stop codon 지정

하나의 codon 은 하나의 amino acid 를 만들고 amino acid 가 결합하여 단백질을 형성한다 .

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Genetic Code: 3 bases=1amino acidGenetic Code: 3 bases=1amino acid

FirstPosition(5’ end)T

C

A

G

T C A G

Second positionThirdPosition(3’ end)T

CAG

TCAG

TCAGTCAG

PhePheLeuLeuLeuLeuLeuLeu

llelleLleMet

ValValValVal

AlaAlaAlaAla

ThrThrThrThr

ProProProPro

SerSerSerSer

TyrTyrSTOPSTOPHisHisGlnGlnAsnAsnLysLys

AspAspGluGiu

CysCysSTOPTrpArgArgArgArg

SerSerArgArg

GlyGlyGlyGly

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Protein StructureProtein Structure

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Human Genetic VariationsHuman Genetic Variations(Single Nucleotide Polymorphisms)(Single Nucleotide Polymorphisms) SNP’s- “genetic individuality” ~1/1000 bases variable (2 humans) Make us more/less susceptible to diseases May influence the effect of drug treatments

TTTGCTCCGTTTTCATTTGCTCYGTTTTCATTTGCTCTGTTTTCA

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SNP (Single Nucleotide PolymorpSNP (Single Nucleotide Polymorphism)hism) Finding single nucleotide changes at specific regions of

genes

Diagnosis of hereditary diseases Personal drug Finding more effective drugs and

treatments

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Human IndividualityHuman Individuality

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Flood of Data! (SWISS-PROT)Flood of Data! (SWISS-PROT)

1988 1990 1992 1994 1996

807060504030

2010 0

Year of release

Nu

mb

er

of

seq

uen

ces x

10

00

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How Can We Analyze the Flood How Can We Analyze the Flood of Data?of Data?Data: don’t just store it, analyze it! By com

paring sequences, one can find out about things like ancestors of organisms phylogenetic trees protein structures protein function

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Bioinformatics Is About:Bioinformatics Is About:

Elicitation of DNA sequences from genetic material

Sequence annotation (e.g. with information from experiments)

Understanding the control of gene expression (i.e. under what circumstances proteins are transcribed from DNA)

The relationship between the amino acid sequence of proteins and their structure.

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Aim of Research in BioinformaticsAim of Research in Bioinformatics

Understand the functioning of living things – to “improve the quality of life”.

Drug design Identification of genetic risk factor Gene therapy Genetic modification of good crops and animals, etc

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Extension of Bioinformatics ConcExtension of Bioinformatics Concept ept Genomics

Functional genomics Structural genomics

Proteomics: large scale analysis of the proteins of an organism

Pharmacogenomics: developing new drugs that will target a particular disease

Microarray: DNA chip, protein chip