1. Bioinformatics for Human Biologists Rasmus Wernersson, Associate Professor Center for Biological Sequence Analysis, DTU [ raz@cbs.dtu.dk - http://www.cbs.dtu.dk/~raz/ ]

2. Course outline MondayTuesdayWednesdayThursdayFriday Introduction Evolution & biological information DATA DNA (GenBank) Protein (UniProt) Methods Pairwise alignment BLAST DATA Protein structure (PDB) Methods PyMOL PSI-Blast Methods Multiple alignment Phylogenetic trees DATA Full genome data Methods UCSC Genome browser Prediction methods.

3. DTU survival guide

4. This is a hands-on course The major part of the course is computer exercises We get to use the actual methods We get to use “live” online database Reporting: –Short “log book” on each exercise

5. Everything is linked from the course programme

6. On evolution and sequences Background information

7. Classification: Linnaeus Carl Linnaeus 1707-1778

8. Classification: Linnaeus Hierarchical system –Kingdom –Phylum –Class –Order –Family –Genus –Species

9. Classification depicted as a tree

10. No “mixed” animals Source: www.dr.dk/olinewww.dr.dk/oline

11. Classification depicted as a tree SpeciesGenusFamilyOrderClass

12. Comparison of limbs Image source: http://evolution.berkeley.edu

13. Theory of evolution Charles Darwin 1809-1882

14. Phylogenetic basis of systematics Linnaeus: Ordering principle is God. Darwin: Ordering principle is shared descent from common ancestors. Today, systematics is explicitly based on phylogeny.

15. Natural Selection: Darwin’s four postulates More young are produced each generation than can survive to reproduce. Individuals in a population vary in their characteristics. Some differences among individuals are based on genetic differences. Individuals with favorable characteristics have higher rates of survival and reproduction. Evolution by means of natural selection Presence of ”design-like” features in organisms: Quite often features are there “for a reason”

16. Evolution at the sequence level

17. About DNA DNA contains the recipes of how to make protein / enzymes. Every time a cells divides it’s DNA is duplicated, and each daughter cell gets a copy.

18. The DNA alphabet The information in the DNA is written in a four letter code: A, T, G, C. The DNA can be “sequenced” and the result stored in a computer file. ATGGCCCTGTGGAT

19. DNA is always written 5’  3’ 5’ AGCC 3’ 3’ TCGG 5’ 5’ ATGGCCAGGTAA 3’ DNA backbone: http://en.wikipedia.org/wiki/DNA (Deoxy)ribose: http://en.wikipedia.org/ Ribose 1 23 4 5 Deoxyribose 1 23 4 5 5’ 3’ 5’ 3’

20. ATGGCCCTGTGGATGCG Can DNA be changed?

21. ATGGCCCTGTGGATGCG ATGGCCCTATGGATGCG Can DNA be changed?

22. A history of mutations ATGGCCCTGTGTATGCG ATGGCAATGTGGATGCA ATGGCCCTGTGGATGCG ATGGCCCCGTGGATGCG ATGTCCCCGTGGATGCG ATGGCCCCGTGGAACCG Time

23. Species1: ATGGCAATGTGGATGCA Species2: ATGGCCCCGTGGAACCG Species3: ATGTCCCCGTGGATGCG “DNA alignment” 3 6 5

24. Real life example: Alignment Insulin from 7 different species Homo:ATGGCCCTGTGGATGCGCCTCCTGCCCCTGCTGGCGCTGCTGGCCCTCTGGGGACCTGACCCAGCCGCAGCCTTTGTGAA Pan:ATGGCCCTGTGGATGCGCCTCCTGCCCCTGCTGGTGCTGCTGGCCCTCTGGGGACCTGACCCAGCCTCGGCCTTTGTGAA Sus:ATGGCCCTGTGGACGCGCCTCCTGCCCCTGCTGGCCCTGCTGGCCCTCTGGGCGCCCGCCCCGGCCCAGGCCTTCGTGAA Ovis:ATGGCCCTGTGGACACGCCTGGTGCCCCTGCTGGCCCTGCTGGCACTCTGGGCCCCCGCCCCGGCCCACGCCTTCGTCAA Canis:ATGGCCCTCTGGATGCGCCTCCTGCCCCTGCTGGCCCTGCTGGCCCTCTGGGCGCCCGCGCCCACCCGAGCCTTCGTTAA Mus:ATGGCCCTGTTGGTGCACTTCCTACCCCTGCTGGCCCTGCTTGCCCTCTGGGAGCCCAAACCCACCCAGGCTTTTGTCAA Gallus:ATGGCTCTCTGGATCCGATCACTGCCTCTTCTGGCTCTCCTTGTCTTTTCTGGCCCTGGAACCAGCTATGCAGCTGCCAA

25. Real life example: Tree

26. Interpretation of Multiple Alignments Conserved features assumed to be important for functionality For instance: conserved pairs of cysteines indicate possible disulphide bridge

27. Darwin: all organisms are related through descent with modification Prediction: similar molecules have similar functions in different organisms Protein synthesis carried out by very similar RNA-containing molecular complexes (ribosomes) that are present in all known organisms Sequences are related

28. Sequences are related, II Related oxygen- binding proteins in humans