Date post: | 04-Jan-2016 |
Category: |
Documents |
Upload: | katell-martin |
View: | 22 times |
Download: | 1 times |
Introduction to Bioinformatics
Lecturer: Prof. Yael Mandel-Gutfreund
Teaching Assistance:
Idit kosti
Inbal Tal
Edward Vitkin
Course web site :http://webcourse.cs.technion.ac.il/236523
2
What is Bioinformatics?
3
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..)
4
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 20.3
5
Grading
• 20 % Homework assignments
• 80 % final project
(10% proposal,
20% supervisor evaluation
70% poster presentation)
6
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
7
What is Bioinformatics?
8
“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?
9
Central Paradigm in Molecular Biology
mRNAGene (DNA) Protein
21ST centaury
Genome Transcriptome Proteome
10
From DNA to Genome
Watson and Crick DNA model 1955
1960
1965
1970
1975
1980
1985
11
1995
1990
2000 First human genome draft
First genomeHemophilus Influenzae
Yeast genome
12
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
13
14
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
16
CCTGACAAATTCGACGTGCGGCATTGCATGCAGACGTGCATG
CGTGCAAATAATCAATGTGGACTTTTCTGCGATTATGGAAGAA
CTTTGTTACGCGTTTTTGTCATGGCTTTGGTCCCGCTTTGTTC
AGAATGCTTTTAATAAGCGGGGTTACCGGTTTGGTTAGCGAGA
AGAGCCAGTAAAAGACGCAGTGACGGAGATGTCTGATG CAA
TAT GGA CAA TTG GTT TCT TCT CTG AAT ......
.............. TGAAAAACGTA
Annotation
17
Annotation
Identify the genes within a given sequence of DNA
Identify the sitesWhich regulate the gene
Predict the function
18
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…
19
Using Bioinformatics approaches for Gene hunting
Relative easy in simple organisms (e.g. bacteria)
VERY HARD for higher organism (e.g. humans)
20
Comparativegenomics
21
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 ??
22
Human ATAGCGGGGGGATGCGGGCCCTATACCCChimp ATAGGGG--GGATGCGGGCCCTATACCCMouse ATAGCG---GGATGCGGCGC-TATACC-A
Human ATAGCGGGGGGATGCGGGCCCTATACCCChimp ATAGGGGGGATGCGGGCCCTATACCCMouse ATAGCGGGATGCGGCGCTATACCA
23
And where are we similar ???
VERY SIMAILARConserved between many organisms
VERYDIFFERENT
24
Functionalgenomics
25
TO BE IS NOT ENOUGH In any time point a gene can be functional or not
26
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??
27
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?
31
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….
32
Biological Databases
The different types of data are collected in database
– Sequence databases – Structural databases– Databases of Experimental Results
All databases are connected
33
Sequence databases
• Gene database
• Genome database
• Disease related mutation database
• ………….
34
Genome Browsers
Easy “walk” through the genome
UCSC Genome Browser http://genome.ucsc.edu/
35
Disease related database
36
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/
37
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
38
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
39
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
40
41
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………….
42
PubMed
Service of the National Library of Medicine
http://www.ncbi.nlm.nih.gov/pubmed/
Literature Databases
43
Putting it all Together
• Each Database contains specific information
• Like other biological systems also these databases are interrelated
44
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