Transcript Bioinformatics Tools

Introduction to Bioinformatics
Lecturer: Prof. Yael Mandel-Gutfreund
Teaching Assistance:
Rachelly Normand
Edward Vitkin
Course web site :
http://webcourse.cs.technion.ac.il/236523
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 Structure
1.
2.
2 hours Lecture
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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What is Bioinformatics?
“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.
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Central Paradigm in Molecular Biology
Gene (DNA)
mRNA
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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1990
First genome
Hemophilus Influenzae
1995
Yeast genome
2000
First human
genome draft
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Complete Genomes
Total
2010
1379
2005
294
Eukaryotes
133
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Bacteria
1152
235
Archaea
94
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Total complete genomes 10.10.13 = 7381
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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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25000 genomes… What’s Next ?
The “post-genomics” era
Annotation
Comparative
genomics
Functional
genomics
Systems
Biology
Main Goal:
To understand the living cell
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And beyond…
Personalized medicine
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From ….25000 genomes
To…Understanding living cells
Annotation
CCTGACAAATTCGACGTGCGGCATTGCATGCAGACGTGCATG
CGTGCAAATAATCAATGTGGACTTTTCTGCGATTATGGAAGAA
CTTTGTTACGCGTTTTTGTCATGGCTTTGGTCCCGCTTTGTTC
AGAATGCTTTTAATAAGCGGGGTTACCGGTTTGGTTAGCGAGA
AGAGCCAGTAAAAGACGCAGTGACGGAGATGTCTGATG CAA
TAT GGA CAA TTG GTT TCT TCT CTG AAT ......
.............. TGAAAAACGTA
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Identify the genes within a
given sequence of DNA
Identify the sites
Which regulate the gene
Annotation
Predict the function
What do they do???
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How do we identify a gene
in 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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Comparative
genomics
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Perhaps not surprising!!!
How humans
are chimps?
Comparison between the full drafts of the human and chimp genomes
revealed that they differ only by 1.23%
How can we be so similar--and yet so different?
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Where are we different ??
Where are we similar ???
VERY
DIFFERENT
VERY SIMAILAR
Conserved between
many organisms
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Sometime minor changes in critical genes
can make a big difference
Human ATAGCGGGGGGATGCGGGCCCTATACCC
Chimp ATAGGGGGGATGCGGGCCCTATACCC
Mouse ATAGCGGGATGCGGCGCTATACCA
Human ATAGCGGGGGGATGCGGGCCCTATACCC
Chimp ATAGGGG--GGATGCGGGCCCTATACCC
Mouse ATAGCG---GGATGCGGCGC-TATACC-A
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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
GGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGC
AGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATG
CTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGC
TCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGAT
CCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCA
CCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCA
CTAAGCTCGCTTTCTTGCTGTCCAATTTCTATTAAAGGTTCCTTTGTTCCCTAAGTCCAACTACTAAACT
GGGGGATATTATGAAGGGCCTTGAGCATCTGGATTCTGCCTAATAAAAAACATTTATTTTCATTGC
>gi|4504349|ref|NP_000509.1| beta globin [Homo sapiens]
EEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLG
MVHLTP
AFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVAN
ALAHKYH
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Diseased Individual
>gi|28302128|ref|NM_000518.4| Homo sapiens hemoglobin, beta (HBB), mRNA
ACATTTGCTTCTGACACAACTGTGTTCACTAGCAACCTCAAACAGACACCATGGTGCATCTGACTCCTGA
GGTGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGC
AGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATG
CTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGC
TCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGAT
CCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCA
CCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCA
CTAAGCTCGCTTTCTTGCTGTCCAATTTCTATTAAAGGTTCCTTTGTTCCCTAAGTCCAACTACTAAACT
GGGGGATATTATGAAGGGCCTTGAGCATCTGGATTCTGCCTAATAAAAAACATTTATTTTCATTGC
>gi|4504349|ref|NP_000509.1| beta globin [Homo sapiens]
VEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLG
MVHLTP
AFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVAN
ALAHKYH
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Functional
genomics
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TO BE IS NOT ENOUGH
In any time point a gene can be functional or not
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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
Systems
Biology
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Biological networks
Jeong et al. Nature 411, 41 - 42 (2001)
What can we learn from
Biological Networks
What can we
learn about this
protein
• Is the protein essential for the organism ?
• Is it a good drug targets?
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?
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 proteins
ETC….
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Main Topics
1. Introduction to bioinformatics
2. Pairwise alignment
3. Database search
4. Protein alignments
5. MSA and phylogenetic analysis
6. Sequencing
7. Motif search-function prediction
8. Gene expression
9. Structural bioinformatics
(proteins and RNA)
10. Biological networks
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