Introduction to Bioinformatics

Lecturer: Prof. Yael Mandel-Gutfreund

Teaching Assistance:

Rachelly Normand

Edward Vitkin

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 19.3

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Grading

• 20 % Homework assignments

• 80 % final project

(10% proposal,

20% supervisor evaluation

70% poster presentation)

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Literature list• 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

Total complete genomes 10.10.13 = 7381

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

And beyond…Personalized medicine

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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 functionWhat do they do???

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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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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 can we be so similar--and yet so different?

How humans are chimps?

Perhaps not surprising!!!

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Where are we different ??

Where are we similar ???

VERY SIMAILARConserved between many organisms

VERYDIFFERENT

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

Human ATAGCGGGGGGATGCGGGCCCTATACCCChimp ATAGGGGGGATGCGGGCCCTATACCCMouse ATAGCGGGATGCGGCGCTATACCA

Sometime minor changes in critical genes can make a big difference

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Single change in a genes among humans can be responsible for sever diseases

Sickle Cell Anemia

Due to 1 swapping of an A for a T

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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Functionalgenomics

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

The difference in the brain size between Human and apes is mainly related to the different levels of the genes expression and not their content

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Systems Biology

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

Biological networks

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

How can bioinformatics contribute to Medicine?

http://www.tedmed.com/talks/show?id=17961

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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 genomes- Infer the function of the genes and proteins- Analyze the interactions between genes and proteinsETC….

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Main Topics

1. Introduction to bioinformatics2. Pairwise alignment3. Database search4. Protein alignments5. MSA and phylogenetic analysis6. Sequencing7. Motif search-function prediction8. Gene expression9. Structural bioinformatics (proteins and RNA)10. Biological networks