Course Sequence Analysis for Bioinformatics Master’s
-
Upload
lysandra-dodson -
Category
Documents
-
view
34 -
download
0
description
Transcript of Course Sequence Analysis for Bioinformatics Master’s
![Page 1: Course Sequence Analysis for Bioinformatics Master’s](https://reader036.fdocuments.net/reader036/viewer/2022062304/56813177550346895d97f075/html5/thumbnails/1.jpg)
Course Sequence Analysisfor Bioinformatics Master’s
Bart van Houte, Radek Szklarczyk, Victor Simossis, Jens Kleinjung, Jaap Heringa
[email protected], http://ibivu.cs.vu.nl, Tel. 47649, Rm R4.41
![Page 2: Course Sequence Analysis for Bioinformatics Master’s](https://reader036.fdocuments.net/reader036/viewer/2022062304/56813177550346895d97f075/html5/thumbnails/2.jpg)
Sequence Analysis course scheduleLectures
[wk 45] 01/11/04 Introduction Lecture 1[wk 45] 04/11/04 Sequence Alignment 1 Lecture 2[wk 46] 08/11/04 Sequence Alignment 2 Lecture 3[wk 46] 11/11/04 Sequence Alignment 3 Lecture 4[wk 47] 15/11/04 Multiple Sequence Alignment 1 Lecture 5[wk 47] 18/11/04 Multiple Sequence Alignment 2 Lecture 6[wk 48] 22/11/04 Multiple Sequence Alignment 3 Lecture 7[wk 48] 25/11/04 Sequence Databank Searching 1Lecture 8[wk 49] 29/11/04 Sequence Databank Searching 2Lecture 9[wk 49] 02/12/04 Pattern Matching 1 Lecture 10[wk 50] 06/12/04 Pattern Matching 2 Lecture 11[wk 50] 09/12/04 Genome Analysis Lecture 12[wk 51] 13/12/04 (lecture rm TBA)
Phylogenetics/Overview Lecture 13
![Page 3: Course Sequence Analysis for Bioinformatics Master’s](https://reader036.fdocuments.net/reader036/viewer/2022062304/56813177550346895d97f075/html5/thumbnails/3.jpg)
Sequence Analysis course schedulePractical assignments
• There will be four practical assignments you will have to carry out. Each assignment will be introduced and placed on the IBIVU website:
1. Pairwise alignment (DNA and protein) (Victor/Radek)2. Multiple sequence alignment (insulin family) (Victor)3. Pattern recognition (Jens)4. Database searching (Jens)
• Optionally, you can further do an assignment on programming your own sequence analysis method (assignment ‘Dynamic programming’ supervised by Bart). This assignment will give you bonus points for your final mark but is not required.
![Page 4: Course Sequence Analysis for Bioinformatics Master’s](https://reader036.fdocuments.net/reader036/viewer/2022062304/56813177550346895d97f075/html5/thumbnails/4.jpg)
Sequence Analysis course final mark
Task Fraction1. Oral exam 1/2
2. Assignment Pairwise alignment 1/8
3. Assignment Multiple sequence alignment 1/8
4. Assignment Pattern recognition 1/8
5. Assignment Database searching 1/8
6. Optional assignment 1/8 (bonus)
Dynamic programming
![Page 5: Course Sequence Analysis for Bioinformatics Master’s](https://reader036.fdocuments.net/reader036/viewer/2022062304/56813177550346895d97f075/html5/thumbnails/5.jpg)
Bioinformatics staff for this course
• Jens Kleinjung – UD (1/11/02)
• Victor Simossis – PhD (1/12/02)
• Radek Szklarczyk - PhD (1/03/03)
• Bart van Houte – PhD (1/09/04)
• Jaap Heringa – Grpldr (1/10/02)
![Page 6: Course Sequence Analysis for Bioinformatics Master’s](https://reader036.fdocuments.net/reader036/viewer/2022062304/56813177550346895d97f075/html5/thumbnails/6.jpg)
Gathering knowledge
• Anatomy, architecture
• Dynamics, mechanics
• Informatics(Cybernetics – Wiener, 1948) (Cybernetics has been defined as the science of control in machines and animals, and hence it applies to technological, animal and environmental systems)
• Genomics, bioinformatics
Rembrandt, 1632
Newton, 1726
![Page 7: Course Sequence Analysis for Bioinformatics Master’s](https://reader036.fdocuments.net/reader036/viewer/2022062304/56813177550346895d97f075/html5/thumbnails/7.jpg)
MathematicsStatistics
Computer ScienceInformatics
BiologyMolecular biology
Medicine
Chemistry
Physics
Bioinformatics
Bioinformatics
![Page 8: Course Sequence Analysis for Bioinformatics Master’s](https://reader036.fdocuments.net/reader036/viewer/2022062304/56813177550346895d97f075/html5/thumbnails/8.jpg)
Bioinformatics
“Studying informational processes in biological systems” (Hogeweg, early
1970s)• No computers necessary• Back of envelope OK
Applying algorithms with mathematical formalisms in biology (genomics) -- USA
“Information technology applied to the management and analysis of biological data” (Attwood and Parry-Smith)
![Page 9: Course Sequence Analysis for Bioinformatics Master’s](https://reader036.fdocuments.net/reader036/viewer/2022062304/56813177550346895d97f075/html5/thumbnails/9.jpg)
Bioinformatics in the olden days• Close to Molecular Biology:
– (Statistical) analysis of protein and nucleotide structure
– Protein folding problem– Protein-protein and protein-nucleotide
interaction
• Many essential methods were created early on (BG era)– Protein sequence analysis (pairwise and
multiple alignment)– Protein structure prediction (secondary, tertiary
structure)
![Page 10: Course Sequence Analysis for Bioinformatics Master’s](https://reader036.fdocuments.net/reader036/viewer/2022062304/56813177550346895d97f075/html5/thumbnails/10.jpg)
Bioinformatics in the olden days (Cont.)
• Evolution was studied and methods created– Phylogenetic reconstruction (clustering – NJ
method
![Page 11: Course Sequence Analysis for Bioinformatics Master’s](https://reader036.fdocuments.net/reader036/viewer/2022062304/56813177550346895d97f075/html5/thumbnails/11.jpg)
But then the big bang….
![Page 12: Course Sequence Analysis for Bioinformatics Master’s](https://reader036.fdocuments.net/reader036/viewer/2022062304/56813177550346895d97f075/html5/thumbnails/12.jpg)
The Human Genome -- 26 June 2000
Dr. Craig Venter
Celera Genomics
-- Shotgun method
Sir John Sulston
Human Genome Project
![Page 13: Course Sequence Analysis for Bioinformatics Master’s](https://reader036.fdocuments.net/reader036/viewer/2022062304/56813177550346895d97f075/html5/thumbnails/13.jpg)
Human DNA
• There are about 3bn (3 109) nucleotides in the nucleus of almost all of the trillions (3.5 1012 ) of cells of a human body (an exception is, for example, red blood cells which have no nucleus and therefore no DNA) – a total of ~1022 nucleotides!
• Many DNA regions code for proteins, and are called genes (1 gene codes for 1 protein in principle)
• Human DNA contains ~30,000 expressed genes • Deoxyribonucleic acid (DNA) comprises 4 different
types of nucleotides: adenine (A), thiamine (T), cytosine (C) and guanine (G). These nucleotides are sometimes also called bases
![Page 14: Course Sequence Analysis for Bioinformatics Master’s](https://reader036.fdocuments.net/reader036/viewer/2022062304/56813177550346895d97f075/html5/thumbnails/14.jpg)
Human DNA (Cont.)
• All people are different, but the DNA of different people only varies for 0.2% or less. So, only 2 letters in 1000 are expected to be different. Over the whole genome, this means that about 3 million letters would differ between individuals.
• The structure of DNA is the so-called double helix, discovered by Watson and Crick in 1953, where the two helices are cross-linked by A-T and C-G base-pairs (nucleotide pairs – so-called Watson-Crick base pairing).
• The Human Genome has recently been announced as complete (in 2004).
![Page 15: Course Sequence Analysis for Bioinformatics Master’s](https://reader036.fdocuments.net/reader036/viewer/2022062304/56813177550346895d97f075/html5/thumbnails/15.jpg)
Genome sizeGenome sizeOrganism Number of base pairs
X-174 virus 5,386
Epstein Bar Virus 172,282
Mycoplasma genitalium 580,000
Hemophilus Influenza 1.8 106
Yeast (S. Cerevisiae) 12.1 106
Human Human 3.2 3.2 10 1099
Wheat 16 109
Lilium longiflorum 90 109
Salamander 100 109
Amoeba dubia 670 109
![Page 16: Course Sequence Analysis for Bioinformatics Master’s](https://reader036.fdocuments.net/reader036/viewer/2022062304/56813177550346895d97f075/html5/thumbnails/16.jpg)
Humans have spliced genes…Humans have spliced genes…
![Page 17: Course Sequence Analysis for Bioinformatics Master’s](https://reader036.fdocuments.net/reader036/viewer/2022062304/56813177550346895d97f075/html5/thumbnails/17.jpg)
Protein
mRNA
DNA
transcription
translation
CCTGAGCCAACTATTGATGAA
PEPTIDE
CCUGAGCCAACUAUUGAUGAA
A gene codes for a proteinA gene codes for a protein
![Page 18: Course Sequence Analysis for Bioinformatics Master’s](https://reader036.fdocuments.net/reader036/viewer/2022062304/56813177550346895d97f075/html5/thumbnails/18.jpg)
Genome information has changed bioinformatics
• More high-throughput (HTP) applications (cluster computing, GRID, etc.)
• More automatic pipeline applications• More user-friendly interfaces• Greater emphasis on biostatistics• Greater influence of computer science (machine
learning, software engineering, etc.)• More integration of disciplines, databases and
techniques
![Page 19: Course Sequence Analysis for Bioinformatics Master’s](https://reader036.fdocuments.net/reader036/viewer/2022062304/56813177550346895d97f075/html5/thumbnails/19.jpg)
Protein Sequence-Structure-FunctionProtein Sequence-Structure-Function
Sequence
Structure
Function
Threading
Homology searching (BLAST)
Ab initio prediction and folding
Function prediction from structure
![Page 20: Course Sequence Analysis for Bioinformatics Master’s](https://reader036.fdocuments.net/reader036/viewer/2022062304/56813177550346895d97f075/html5/thumbnails/20.jpg)
Luckily for bioinformatics…
• There are many annotated databases (i.e. DBs with experimentally verified information)
• We can relate biological macromolecules using evolution and then “steal” annotation of “neighbouring” proteins or DNA in the DB
• This works for sequence as well as structural information
• Problem we discuss in this course: how do we score the evolutionary relationships; i.e. we need to develop a measure to decide which molecules are (probably) neighbours and which are not
![Page 21: Course Sequence Analysis for Bioinformatics Master’s](https://reader036.fdocuments.net/reader036/viewer/2022062304/56813177550346895d97f075/html5/thumbnails/21.jpg)
Modern bioinformatics is closely associated with genomics
• The aim is to solve the genomics information problem
• Ultimately, this should lead to biological understanding how all the parts fit (DNA, RNA, proteins, metabolites) and how they interact (gene regulation, gene expression, protein interaction, metabolic pathways, protein signalling, etc.)