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Bioinformatics Ch1. Introduction 阮阮阮 2002, Oct 17 NTUST ww.ntut.edu.tw/~yukijuan/lectures/bioinfo/Oct17.ppt
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Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

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Page 1: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

BioinformaticsCh1. Introduction

阮雪芬2002, Oct 17NTUST

www.ntut.edu.tw/~yukijuan/lectures/bioinfo/Oct17.ppt

Page 2: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

Outline

A scenario Life in space and time Dogmas: central and peripheral Observable and data archives

Page 3: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

Traditional and Current Biology

Traditionally, biology has been an observational science.

Now, biology has been converted into deductive science.

Page 4: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

The Data of Bioinformatics Very very large amount Nucleotide sequence databanks

contain 16 x 109 bases The full three-dimensional

coordinates of proteins of average length ~400 residues: 16000 entries

Not only are the individual databanks large, but their sizes are increasing as a very high rate.

Page 5: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

GenBank

Page 6: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

Goals

“Saw life clearly and saw it whole”

To interrelate sequence, three-dimensional structure, interactions, and function of individual proteins, nucleic acids and protein-nucleic acid complexes

Understand integrative aspects of the biology of organisms

Page 7: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

Goals

To deduce events in evolutionary history.

To support application to medicine, agriculture and other scientific fields.

Page 8: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

A Scenario

Page 9: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

Imagine a Crisis (1)

A new biological virus creates an epidemic of fatal disease in humans or animals Laboratory scientists will

isolate its genetic material-a molecule of nucleic acid and determine the sequence.

Computer program will then take over

Page 10: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

Imagine a Crisis (2)

Screening this new genome against a data bank of all know genetic messages

Developing antiviral therapies: virus contain protein molecules which are suitable targets, for drugs that will interfere with viral structure or function

Page 11: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

Imagine a Crisis (3)From the viral DNA sequences

Protein sequence

Computer program

Page 12: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

Imagine a Crisis (4)

From amino acid sequences

Three-dimensional structure

Computer program

Page 13: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

Homology Modelling

Data bank will be screened for related proteins of know structures

Structure will be predicted

AB

Computer program

Page 14: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

Ab initio

No related protein of known structure is found

Ab initio

Predicting the structure

Page 15: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

Design Therapeutic Agents

Knowing the viral protein structure

Design therapeutic agents

Page 16: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

Life in space and time

Page 17: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

In Space

Biosphere Ecosystem Darwinian selection or genetic drift

Natural mutation The recombination of genes in sexual reproduction

Direct gene transfer

The generation of variants

Page 18: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

In Space

Ecosystem

Species

Cell

Nuclei, organelles and cytoskeleton

Molecules

Page 19: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

In Time

A history of life 3.5 billion years

Page 20: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

Dogmas: Central and Peripheral

Page 21: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

Central Dogmas 1957, Crick 提出中心教條” DNA 製造

RNA , RNA 製造蛋白質” 中心教條大體上是對的,但也有些需要修正

有許多 RNA 病毒: RNADNARNAProtein 跳躍基因 真核細胞 RNA 需要經過剪接 不只蛋白質具酵素功能,某些 RNA 也具酵素功能 某些基因可經不同的轉錄起始點或不同的剪接方式,

製備出多種 RNA ,而轉錄成功能不同的蛋白質

Page 22: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

真核細胞 RNA 需要經過剪接

Page 23: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

不只蛋白質具酵素功能,某些 RNA 也具酵素功能

First identified in plant virus

Page 24: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.
Page 25: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

Purines and Pyrimidines

Page 26: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

The Strand in the Double-helix are Antiparalle

5’ 3’

3’

5’

Page 27: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.
Page 28: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

Paradigm

DNA sequence

Protein sequence

Protein structure

Protein function

determines

determines

determines

Most of the organized activity of bioinformatics has been focused on the analysis of the data related to these processes

Page 29: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

Observable and Data Archives

Page 30: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

A Databank

An archive of information A logical organization Structure of that information Tools to gain access to it

Page 31: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

A Databank in Molecular Biology

Archival databanks of biological information DNA and protein sequence Nucleic acid and protein structure Databanks of protein expression

Page 32: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

A Databank in Molecular Biology

Derived Databanks Sequence motifs Mutations and variants in DNA and protein

sequences Classification and relationships

Bibliographic Databanks Databanks of web sites

Databanks of databanks containing biological information

Links between databanks

Page 33: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

The Mechanism of Access to a Databank is

the Set of Tools for answering Question Such as: Does the databank contain the

information I require? How can I assemble information from the

databank in a useful form? Indices of databanks are useful in asking

” Where can I find some specific piece of information?”

Page 34: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

Give a sequence or fragment of a sequence

Find sequence in the database that are similar to it

A central problem in bioinformatics

A Variety of Possible Kinds of Database Queries Can Arise in Bioinformatics (1)

Page 35: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

Give a protein structure or fragment

Find protein structures in the database that are similar to it

A Variety of Possible Kinds of Database Queries Can Arise in Bioinformatics (2)

Page 36: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

Give a sequence of a protein of unknown structure

Find structures in the database that adopt similar three-dimensional structures

A Variety of Possible Kinds of Database Queries Can Arise in Bioinformatics (3)

Page 37: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

A Variety of Possible Kinds of Database Queries Can Arise in Bioinformatics (3)

For if two protein have sufficiently similar sequences

They will have similar structure

Page 38: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

A Variety of Possible Kinds of Database Queries Can Arise in Bioinformatics (4)

Give a protein structure

Find sequences in the data bank that correspond to similar structures

Page 39: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

A Variety of Possible Kinds of Database Queries Can Arise in Bioinformatics

(1) and (2) are solved problems (3) and (4) are active fields of

research

Page 40: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

Curation, Annotation and Quality Control

Older data were limited by older techniques Amino acid sequences of protein used to

be determined by peptide sequencing. Now, almost al are translated from DNA

sequences.

Page 41: Bioinformatics Ch1. Introduction 阮雪芬 2002, Oct 17 NTUST yukijuan/lectures/bioinfo/Oct17.ppt.

Curation, Annotation and Quality Control

Distributed error-correction and annotation

Dynamic error-correction and annotation