An interactive lesson to kick off a course in introductory bioinformatics

2. What is bioinformatics? Morten Lindow Bioinformatics Centre University of Copenhagen

3. A big change in biology has taken place Measure the expression of a single gene in a single sample Measure the expression of all genes in many samples Before Now

4. Before  Now Find interaction partners for one protein (co immunoprecipitation -> western blot) Find interaction partners for all proteins (yeast two-hybrid – phage display)

5. Biology has become an information science GGCAAACCCTGTGATTCAGTTTGTCTGTGATTTGCTTAACCGGGATATTTCTTCTCGACCTTTATCTGATGCTGATCGTG TTAAGATAAAAAAGGCTCTTAGAGGTGTCAAAGTTGAAGTGACTCATCGAGGAAACATGCGCCGGAAGTACCGCATTTCC GGTTTGACTGCTGTGGCCACTCGGGAATTGACATTCCCAGTAGATGAAAGAAATACTCAGAAATCTGTTGTAGAATACTT CCACGAAACATATGGTTTTCGCATTCAGCACACTCAACTACCATGCTTGCAAGTTGGGAATTCTAATAGGCCTAATTACT TACCAATGGAGGTATGCAAGATTGTTGAAGGCCAGCGGTATTCCAAAAGATTGAATGAGAGACAGATCACTGCTTTGCTG AAGGTTACCTGTCAGCGCCCGATAGATCGAGAAAAAGATATCTTACAGACGGTGCAACTCAATGATTATGCTAAAGATAA TTATGCTCAAGAGTTTGGCATCAAAATAAGTACTTCTCTGGCTTCTGTTGAGGCTCGTATACTGCCTCCTCCATGGCTTA AGTACCACGAGTCTGGAAGGGAAGGGACTTGTCTGCCACAAGTTGGTCAATGGAACATGATGAATAAGAAAATGATCAAT GGTGGAACGGTGAATAATTGGATCTGCATCAACTTTTCTAGGCAAGTGCAGGACAATCTAGCGCGTACATTTTGTCAGGA ACTTGCTCAAATGTGTTACGTATCTGGCATGGCATTTAATCCGGAACCAGTCCTCCCACCAGTCAGTGCTCGCCCTGAGC AAGTAGAGAAGGTCTTGAAGACTAGATATCATGATGCCACATCAAAACTCTCCCAAGGAAAAGAAATTGATCTGCTTATT GTCATTCTGCCCGATAATAATGGATCATTATACGGTGATTTGAAACGCATATGTGAGACTGAACTCGGCATAGTCTCTCA ATGTTGCCTGACAAAGCATGTCTTTAAGATGAGCAAACAATACATGGCTAATGTTGCGCTGAAGATTAATGTGAAGGTTG GAGGAAGAAACACAGTGCTTGTTGATGCTCTATCTAGGCGGATTCCTCTAGTCAGTGATCGACCCACCATTATATTTGGT GCTGATGTTACCCACCCTCACCCTGGAGAGGATTCAAGCCCATCTATTGCTGCTGTTGTGGCATCTCAGGATTGGCCTGA AATCACTAAATATGCTGGATTAGTTTGCGCTCAAGCGCATAGGCAGGAGCTCATTCAGGATCTGTTCAAAGAGTGGAAGG ATCCTCAGAAAGGTGTGGTGACTGGTGGCATGATAAAGGAGTTGCTCATAGCCTTCCGTAGATCAACTGGGCATAAACCA CTAAGGATCATCTTCTACAGGGATGGAGTCAGTGAGGGACAATTTTACCAAGTTTTGCTCTATGAACTTGATGCCATCCG CAAGGCCTGTGCTTCGCTGGAAGCAGGTTATCAACCACCAGTGACATTTGTGGTGGTGCAGAAGCGTCATCACACGAGGC TGTTTGCTCAGAACCACAATGATCGCCATTCGGTGGACAGAAGTGGGAATATTTTACCTGGCACTGTTGTGGACTCTAAA ATCTGCCACCCTACAGAGTTTGACTTTTACCTCTGTAGTCATGCTGGTATTCAGGGCACTTCTCGACCTGCTCATTACCA CGTTCTTTGGGATGAGAACAACTTTACTGCAGATGGACTTCAATCTCTGACCAATAACTTATGTTACACGTATGCAAGAT GCACACGCTCAGTTTCAATTGTTCCCCCTGCATATTATGCACATCTAGCAGCTTTTAGGGCTCGATTCTACATGGAGCCA GAGACATCAGACAGTGGCTCAATGGCTAGTGGGAGCATGGCACGTGGAGGTGGAATGGCTGGTAGAAGCACACGCGGGCC TAATGTCAATGCTGCAGTGAGGCCACTCCCAGCTCTGAAAGAGAATGTGAAGCGTGTCATGTTCTACTGCTGAGTTGATT CACCCTCTATCTATCTTTATGACCTAAATTAATGAAGAATATCATGTATGCTTTCTAAGACTTATCGTGTGTTTGGATAT TTCATCACTCTTTCTCTATGAGTATGAGATGCTTTATGACTCTTGTTTGACAACTACTAAACTTTATTATTCAAAACAGA CTTTGATCCTTTCAAAAAAAAAAAAAAAAAAAA TAGAGAGAGAGAGAAAGATATAGAGAGAACACAGAGAGGCGAGAGCGACGTAGGGTTGGTGTTTCGTACGGATTTTCTCG GTCAATCCTAGTTTCTCCGGCGAGAGATTGCTTTTCAGGAATCATCATGGTGAGAAAGAGAAGAACGGATGCTCCATCTG AAGGAGGTGAAGGCTCTGGGTCTCGTGAAGCTGGTCCAGTCTCAGGTGGTGGACGTGGTTCACAGCGAGGTGGTTTCCAG CAGGGAGGAGGACAACACCAAGGTGGAAGGGGTTATACTCCTCAACCTCAACAGGGAGGTCGTGGTGGTCGTGGATATGG GCAACCACCACAACAGCAACAACAGTATGGAGGACCACAAGAGTACCAAGGAAGAGGAAGAGGAGGACCTCCTCATCAAG GAGGTCGAGGAGGGTATGGCGGTGGCCGTGGAGGTGGACCTTCTTCTGGACCACCGCAGAGACAATCAGTTCCCGAGCTG CATCAAGCTACCTCACCTACTTATCAAGCGGTGTCTTCTCAGCCTACACTGTCTGAGGTGAGTCCTACCCAGGTACCAGA ACCTACTGTTCTGGCTCAGCAATTTGAACAACTCTCTGTTGAACAAGGAGCTCCCAGTCAGGCAATCCAGCCTATACCGT CTTCTAGCAAGGCTTTCAAGTTTCCAATGAGGCCTGGTAAAGGACAGAGTGGAAAGCGTTGCATTGTGAAGGCTAACCAT TTCTTTGCTGAACTGCCTGATAAGGATTTGCACCATTATGATGTTACCATTACTCCGGAAGTTACATCAAGGGGTGTCAA TCGTGCTGTGATGAAACAACTTGTTGATAATTATCGTGATTCTCACCTTGGAAGTCGTCTTCCAGCGTATGATGGTCGAA AAAGTCTTTACACTGCTGGTCCACTTCCCTTTAACTCCAAGGAGTTCAGAATCAATCTTCTTGACGAAGAAGTAGGGGCT GGAGGTCAAAGACGAGAAAGGGAATTTAAAGTTGTGATCAAGCTAGTTGCACGTGCTGATCTGCATCACCTAGGAATGTT TTTGGAGGGGAAACAATCAGATGCCCCACAGGAAGCTCTGCAGGTTCTTGACATTGTTCTTCGTGAGCTGCCGACCTCTA GGTATATTCCGGTGGGCCGGTCCTTTTATTCCCCTGATATAGGAAAAAAACAATCATTGGGGGATGGCTTGGAGAGCTGG CGTGGATTCTACCAAAGCATTCGTCCTACACAGATGGGCTTATCACTCAATATTGATATGTCATCGACAGCCTTCATAGA GGCAAACCCTGTGATTCAGTTTGTCTGTGATTTGCTTAACCGGGATATTTCTTCTCGACCTTTATCTGATGCTGATCGTG TTAAGATAAAAAAGGCTCTTAGAGGTGTCAAAGTTGAAGTGACTCATCGAGGAAACATGCGCCGGAAGTACCGCATTTCC GGTTTGACTGCTGTGGCCACTCGGGAATTGACATTCCCAGTAGATGAAAGAAATACTCAGAAATCTGTTGTAGAATACTT CCACGAAACATATGGTTTTCGCATTCAGCACACTCAACTACCATGCTTGCAAGTTGGGAATTCTAATAGGCCTAATTACT TACCAATGGAGGTATGCAAGATTGTTGAAGGCCAGCGGTATTCCAAAAGATTGAATGAGAGACAGATCACTGCTTTGCTG AAGGTTACCTGTCAGCGCCCGATAGATCGAGAAAAAGATATCTTACAGACGGTGCAACTCAATGATTATGCTAAAGATAA TTATGCTCAAGAGTTTGGCATCAAAATAAGTACTTCTCTGGCTTCTGTTGAGGCTCGTATACTGCCTCCTCCATGGCTTA AGTACCACGAGTCTGGAAGGGAAGGGACTTGTCTGCCACAAGTTGGTCAATGGAACATGATGAATAAGAAAATGATCAAT GGTGGAACGGTGAATAATTGGATCTGCATCAACTTTTCTAGGCAAGTGCAGGACAATCTAGCGCGTACATTTTGTCAGGA ACTTGCTCAAATGTGTTACGTATCTGGCATGGCATTTAATCCGGAACCAGTCCTCCCACCAGTCAGTGCTCGCCCTGAGC AAGTAGAGAAGGTCTTGAAGACTAGATATCATGATGCCACATCAAAACTCTCCCAAGGAAAAGAAATTGATCTGCTTATT GTCATTCTGCCCGATAATAATGGATCATTATACGGTGATTTGAAACGCATATGTGAGACTGAACTCGGCATAGTCTCTCA ATGTTGCCTGACAAAGCATGTCTTTAAGATGAGCAAACAATACATGGCTAATGTTGCGCTGAAGATTAATGTGAAGGTTG GAGGAAGAAACACAGTGCTTGTTGATGCTCTATCTAGGCGGATTCCTCTAGTCAGTGATCGACCCACCATTATATTTGGT GCTGATGTTACCCACCCTCACCCTGGAGAGGATTCAAGCCCATCTATTGCTGCTGTTGTGGCATCTCAGGATTGGCCTGA AATCACTAAATATGCTGGATTAGTTTGCGCTCAAGCGCATAGGCAGGAGCTCATTCAGGATCTGTTCAAAGAGTGGAAGG ATCCTCAGAAAGGTGTGGTGACTGGTGGCATGATAAAGGAGTTGCTCATAGCCTTCCGTAGATCAACTGGGCATAAACCA CTAAGGATCATCTTCTACAGGGATGGAGTCAGTGAGGGACAATTTTACCAAGTTTTGCTCTATGAACTTGATGCCATCCG CAAGGCCTGTGCTTCGCTGGAAGCAGGTTATCAACCACCAGTGACATTTGTGGTGGTGCAGAAGCGTCATCACACGAGGC TGTTTGCTCAGAACCACAATGATCGCCATTCGGTGGACAGAAGTGGGAATATTTTACCTGGCACTGTTGTGGACTCTAAA ATCTGCCACCCTACAGAGTTTGACTTTTACCTCTGTAGTCATGCTGGTATTCAGGGCACTTCTCGACCTGCTCATTACCA CGTTCTTTGGGATGAGAACAACTTTACTGCAGATGGACTTCAATCTCTGACCAATAACTTATGTTACACGTATGCAAGAT GCACACGCTCAGTTTCAATTGTTCCCCCTGCATATTATGCACATCTAGCAGCTTTTAGGGCTCGATTCTACATGGAGCCA GAGACATCAGACAGTGGCTCAATGGCTAGTGGGAGCATGGCACGTGGAGGTGGAATGGCTGGTAGAAGCACACGCGGGCC TAATGTCAATGCTGCAGTGAGGCCACTCCCAGCTCTGAAAGAGAATGTGAAGCGTGTCATGTTCTACTGCTGAGTTGATT CACCCTCTATCTATCTTTATGACCTAAATTAATGAAGAATATCATGTATGCTTTCTAAGACTTATCGTGTGTTTGGATAT TTCATCACTCTTTCTCTATGAGTATGAGATGCTTTATGACTCTTGTTTGACAACTACTAAACTTTATTATTCAAAACAGA Digital genome Environment Organism Tissue Cell Intracellular signaling Current bioinformatics

8. Definition Wikipedia: ”… The terms bioinformatics and computational biology are often used interchangeably. However bioinformatics more properly refers to the creation and advancement of algorithms , computational and statistical techniques, and theory to solve formal and practical problems posed by or inspired from the management and analysis of biological data. Computational biology, on the other hand, refers to hypothesis-driven investigation of a specific biological problem using computers , carried out with experimental and simulated data, with the primary goal of discovery and the advancement of biological knowledge. “

9. Bioinformatics? Search for homologs to a protein sequence Retrieve information about a genome segment Predict the structure of an RNA molecule Build a phylogentic tree connecting a set of proteins Find differentially expressed genes using microarrays Make a model of protein-protein interactions Model the contractions of a muscle Make an equation describing a neuronal action potential Construct cardiac blood-flow model Differential equations to describe prey/predator dynamics

13. Networks between microRNAs and transcription factors In which you will learn a bit about: accessing and searching for information in bio-databases, what microRNAs are, predict RNA structure

17. Summary so far ATCTGCCACCCTACAGAGTTTGACTTTTACCTCTGTAGTCATGCTGGTATTCAGGGCACTTCTCGACCTGCTCATTACCACGTTCTTTGGGATGAGAACAACTTTACTGCAGATGGACTTCAATCTCTGACCAATAACTTATGTTACACGTATGCAAGAT Prediction of precursor structure Identify transcript miRNA gene RNA protein A microRNA

19. Summary so far ATCTGCCACCCTACAGAGTTTGACTTTTACCTCTGTAGTCATGCTGGTATTCAGGGCACTTCTCGACCTGCTCATTACCACGTTCTTTGGGATGAGAACAACTTTACTGCAGATGGACTTCAATCTCTGACCAATAACTTATGTTACACGTATGCAAGAT Prediction of binding sites Prediction of precursor structure Identify transcript miRNA gene RNA protein A microRNA

21. Prediction of microRNA targets ATCTGCCACCCTACAGAGTTTGACTTTTACCTCTGTAGTCATGCTGGTATTCAGGGCACTTCTCGACCTGCTCATTACCACGTTCTTTGGGATGAGAACAACTTTACTGCAGATGGACTTCAATCTCTGACCAATAACTTATGTTACACGTATGCAAGAT Transcriptional unit RNA ?

23. Regulatory systems ATCTGCCACCCTACAGAGTTTGACTTTTACCTCTGTAGTCATGCTGGTATTCAGGGCACTTCTCGACCTGCTCATTACCACGTTCTTTGGGATGAGAACAACTTTACTGCAGATGGACTTCAATCTCTGACCAATAACTTATGTTACACGTATGCAAGAT Maybe feedback regulation? A microRNA Regulates other RNA ( prevents them from being translated to proteins ) Transcriptional unit RNA

24. A feedback loop? miR-155 and Bach ATCTGCCACCCTACAGAGTTTGACTTTTACCTCTGTAGTCATGCTGGTATTCAGGGCACTTCTCGACCTGCTCATTACCACGTTCTTTGGGATGAGAACAACTTTACTGCAGATGGACTTCAATCTCTGACCAATAACTTATGTTACACGTATGCAAGAT BIC - mir-155 Bach2-binding sites (repressor) Bach2-proteins miR-155 “ Lack of BIC and microRNA miR-155 expression in primary cases of Burkitt lymphoma. ” Genes Chromosomes Cancer. 2006 Feb;45(2):147-53 “ These results indicate that BACH2 plays important roles in regulation of B cell development.” Oncogene. 2000 Aug 3;19(33):3739-49

26. Masters of Bioinformatics