Introduction to Bioinformatics236523/234525

Lecturer: Prof. Yael Mandel-Gutfreund

Teaching Assistance:

Shai Ben-Elazar

Idit kosti

Course web site :http://webcourse.cs.technion.ac.il/236523

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What is Bioinformatics?

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Course Objectives

• To introduce the bioinfomatics discipline • To make the students familiar with the major

biological questions which can be addressed by bioinformatics tools

• To introduce the major tools used for sequence and structure analysis and explain in general how they work (limitation etc..)

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Course Structure and Requirements

1.Class Structure1. 2 hours Lecture 2. 1 hour tutorial

2. Home work• Homework assignments will be given every second

week• The homework will be done in pairs.• 5/5 homework assignments will be submitted

2. A final project will be conducted in pairs * Project will be presented as a poster –poster day 14.3

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Grading

• 20 % Homework assignments

• 80 % final project

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Literature list• Gibas, C., Jambeck, P. Developing Bioinformatics

Computer Skills. O'Reilly, 2001. • Lesk, A. M. Introduction to Bioinformatics. Oxford

University Press, 2002.

• Mount, D.W. Bioinformatics: Sequence and Genome Analysis. 2nd ed.,Cold Spring Harbor Laboratory Press, 2004.

Advanced Reading

Jones N.C & Pevzner P.A. An introduction to Bioinformatics algorithms MIT Press, 2004

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What is Bioinformatics?

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“The field of science in which biology, computer science, and information technology merge to form a single discipline”

Ultimate goal: to enable the discovery of new biological insights as well as to create a global perspective from which unifying principles in biology can be discerned.

What is Bioinformatics?

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Central Paradigm in Molecular Biology

mRNAGene (DNA) Protein

21ST centaury

Genome Transcriptome Proteome

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From DNA to Genome

Watson and Crick DNA model 1955

1960

1965

1970

1975

1980

1985

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1995

1990

2000 First human genome draft

First genomeHemophilus Influenzae

Yeast genome

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Total 1379 294

Eukaryotes 133 39

Bacteria 1152 235

Archaea 94 23

Complete Genomes

2010 2005

1,000 Genomes Project: Expanding the Map of Human Genetics

Researchers hope the effort will speed up the discovery of many diseases's genetic roots

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Main Goal:

To understand the living cell

Annotation Comparativegenomics

Functionalgenomics

25000 genomes… What’s Next ?

The “post-genomics” The “post-genomics” eraera

SystemsBiology

From ….25000 genomes

To…Understanding living cells

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CCTGACAAATTCGACGTGCGGCATTGCATGCAGACGTGCATG

CGTGCAAATAATCAATGTGGACTTTTCTGCGATTATGGAAGAA

CTTTGTTACGCGTTTTTGTCATGGCTTTGGTCCCGCTTTGTTC

AGAATGCTTTTAATAAGCGGGGTTACCGGTTTGGTTAGCGAGA

AGAGCCAGTAAAAGACGCAGTGACGGAGATGTCTGATG CAA

TAT GGA CAA TTG GTT TCT TCT CTG AAT ......

.............. TGAAAAACGTA

Annotation

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Annotation

Identify the genes within a given sequence of DNA

Identify the sitesWhich regulate the gene

Predict the function

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How do we identify a genein a genome?

A gene is characterized by several features (promoter, ORF…)some are easier and some harder to detect…

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CCTGACAAATTCGACGTGCGGCATTGCATGCAGACGTGCATG

CGTGCAAATAATCAATGTGGACTTTTCTGCGATTATGGAAGAA

CTTTGTTACGCGTTTTTGTCATGGCTTTGGTCCCGCTTTGTTC

AGAATGCTTTTAATAAGCGGGGTTACCGGTTTGGTTAGCGAGA

AGAGCCAGTAAAAGACGCAGTGACGGAGATGTCTGATG CAA

TAT GGA CAA TTG GTT TCT TCT CTG

AAT .................................

.............. TGAAAAACGTA

TF binding sitepromoter

Ribosome binding SiteORF=Open Reading FrameCDS=Coding Sequence

Transcription

Start Site

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Using Bioinformatics approaches for Gene hunting

Relative easy in simple organisms (e.g. bacteria)

VERY HARD for higher organism (e.g. humans)

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Comparativegenomics

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Comparison between the full drafts of the human and chimp genomesrevealed that they differ only by 1.23%

How humans are chimps?

Perhaps not surprising!!!

So where are we different ??

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Human ATAGCGGGGGGATGCGGGCCCTATACCCChimp ATAGGGG--GGATGCGGGCCCTATACCCMouse ATAGCG---GGATGCGGCGC-TATACC-A

Human ATAGCGGGGGGATGCGGGCCCTATACCCChimp ATAGGGGGGATGCGGGCCCTATACCCMouse ATAGCGGGATGCGGCGCTATACCA

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And where are we similar ???

VERY SIMAILARConserved between many organisms

VERYDIFFERENT

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Functionalgenomics

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TO BE IS NOT ENOUGH In any time point a gene can be functional or not

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From the gene expression pattern we can lean:

What does the gene do ?When is it needed?What other genes or proteins interact with it?…..

What's wrong??

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Systems Biology

Jeong et al. Nature 411, 41 - 42 (2001)

Biological networks

What can we learn from a network?

What can we learn from Biological Networks

• Is the protein essential for the organism ?• Is it a good drug targets?

What can we learn about this protein

What of all this will we learn in the course?

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The course will concentrate on the bioinformatics tools and databases which are used to :Annotate genes, Compare genes and genomesInfer the function of the genes and proteinsAnalyze the interactions between genes and proteinsETC….

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Biological Databases

The different types of data are collected in database

– Sequence databases – Structural databases– Databases of Experimental Results

All databases are connected

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Sequence databases

• Gene database

• Genome database

• Disease related mutation database

• ………….

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Genome Browsers

Easy “walk” through the genome

UCSC Genome Browser http://genome.ucsc.edu/

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Disease related database

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Sickle Cell Anemia

• Due to 1 swapping an A for a T, causing inserted amino acid to be valine instead of glutamine in hemoglobin

Image source: http://www.cc.nih.gov/ccc/ccnews/nov99/

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Healthy Individual>gi|28302128|ref|NM_000518.4| Homo sapiens hemoglobin, beta (HBB), mRNA

ACATTTGCTTCTGACACAACTGTGTTCACTAGCAACCTCAAACAGACACCATGGTGCATCTGACTCCTGA

GGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGCAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAAGCTCGCTTTCTTGCTGTCCAATTTCTATTAAAGGTTCCTTTGTTCCCTAAGTCCAACTACTAAACTGGGGGATATTATGAAGGGCCTTGAGCATCTGGATTCTGCCTAATAAAAAACATTTATTTTCATTGC

>gi|4504349|ref|NP_000509.1| beta globin [Homo sapiens]

MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLG

AFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVAN ALAHKYH

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Diseased Individual>gi|28302128|ref|NM_000518.4| Homo sapiens hemoglobin, beta (HBB), mRNA

ACATTTGCTTCTGACACAACTGTGTTCACTAGCAACCTCAAACAGACACCATGGTGCATCTGACTCCTGA

GGTGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGCAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAAGCTCGCTTTCTTGCTGTCCAATTTCTATTAAAGGTTCCTTTGTTCCCTAAGTCCAACTACTAAACTGGGGGATATTATGAAGGGCCTTGAGCATCTGGATTCTGCCTAATAAAAAACATTTATTTTCATTGC

>gi|4504349|ref|NP_000509.1| beta globin [Homo sapiens]

MVHLTPVEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLG

AFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVAN ALAHKYH

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Structure Databases

• 3-dimensional structures of proteins, nucleic acids, molecular complexes etc

• 3-d data is available due to techniques such as NMR and X-Ray crystallography

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Databases of Experimental Results

• Data such as experimental microarray images- gene expression data

• Proteomic data- protein expression data

• Metabolic pathways, protein-protein interaction data, regulatory networks

• ETC………….

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PubMed

Service of the National Library of Medicine

http://www.ncbi.nlm.nih.gov/pubmed/

Literature Databases

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Putting it all Together

• Each Database contains specific information

• Like other biological systems also these databases are interrelated

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GENOMIC DATAGenBank

DDBJ

EMBL

ASSEMBLED GENOMES

GoldenPath

WormBase

TIGR

PROTEIN

PIR

SWISS-PROT

STRUCTUREPDB

MMDB

SCOP

LITERATURE

PubMed

PATHWAYKEGG

COG

DISEASE

LocusLink

OMIM

OMIA

GENESRefSeq

AllGenes

GDBSNPs

dbSNP

ESTs

dbEST

unigene

MOTIFS

BLOCKS

Pfam

Prosite

GENE EXPRESSION

Stanford MGDB

NetAffx

ArrayExpress