1. Bioinformatics For MNW 2 nd Year Jaap Heringa FEW/FALW Integrative Bioinformatics Institute VU (IBIVU) heringa@cs.vu.nl, www.cs.vu.nl/~ibivu, Tel. 47649, Rm R4.41

2. Current Bioinformatics Unit Jens Kleinjung (1/11/02) Victor Simosis – PhD (1/12/02) Radek Szklarczyk - PhD (1/01/03)

3. Bioinformatics course 2nd year MNW spring 2003 Pattern recognition –Supervised/unsupervised learning –Types of data, data normalisation, lacking data –Search image –Similarity/distance measures –Clustering –Principal component analysis –Discriminant analysis

4. Bioinformatics course 2nd year MNW spring 2003 Protein –Folding –Structure and function –Protein structure prediction –Secondary structure –Tertiary structure –Function –Post-translational modification –Prot.-Prot. Interaction -- Docking algorithm –Molecular dynamics/Monte Carlo

5. Bioinformatics course 2nd year MNW spring 2003 Sequence analysis –Pairwise alignment –Dynamic programming (NW, SW, shortcuts) –Multiple alignment –Combining information –Database/homology searching (Fasta, Blast, Statistical issues-E/P values)

6. Bioinformatics course 2nd year MNW spring 2003 Gene structure and gene finding algorithms Genomics –Expression data, Nucleus to ribosome, translation, etc. –Proteomics, Metabolomics, Physiomics –Databases DNA, EST Protein sequence (SwissProt) Protein structure (PDB) Microarray data Proteomics Mass spectrometry/NMR/X-ray

7. Bioinformatics course 2nd year MNW spring 2003 Bioinformatics method development Programming and scripting languages Web solutions Computational issues –NP-complete problems –CPU, memory, storage problems –Parallel computing Bioinformatics method usage/application Molecular viewers (RasMol, MolMol, etc.)

8. 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

9. Mathematics Statistics Computer Science Informatics Biology Molecular biology Medicine Chemistry Physics Bioinformatics

10. “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)

11. 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)

12. Bioinformatics in the olden days (Cont.) Evolution was studied and methods created –Phylogenetic reconstruction (clustering – NJ method

13. But then the big bang….

14. The Human Genome -- 26 June 2000

15. Dr. Craig Venter Celera Genomics -- Shotgun method Sir John Sulston Human Genome Project

16. Human DNA There are about 3bn (3  10 9 ) nucleotides in the nucleus of almost all of the trillions (3.5  10 12 ) 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 ~10 22 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

17. 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).

18. 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.) More in the next lecture…