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11/18/05 "Omics" Experimental Approaches

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  1. 11/18/05"Omics" Experimental Approaches D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  2. Bioinformatics Seminars Nov 18 Fri 12:10BCB Seminarin E164 Lago Using P-Values for the Planning and Analysis of Microarray Experiments Dan Nettleton, Stat D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  3. Protein Structure PredictionGenome Analysis Mon Protein 3' structure prediction Wed Genome analysis & genome projects Comparative genomics; ENCODE, SNPs, HapMaps, medical genomics Thur Lab Protein structure prediction, SNPs Fri Experimental approaches: microarrays, proteomics, metabolomics, medical genomics D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  4. Reading Assignment (Fri & after break) • Mount Bioinformatics • Chp 13 Microarray Analysis http://www.bioinformaticsonline.org/ch/ch13/index.html • Ck Errata: http://www.bioinformaticsonline.org/help/errata2.html D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  5. BCB 544 Additional Readings • Required: • Human HapMap (Nature 437, Oct 27, 2005) • Commentary (437:1233) http://www.nature.com/nature/journal/v437/n7063/full/4371233a.html • News & Views (437: 1241) http://www.nature.com/nature/journal/v437/n7063/full/4371241a.html • Optional: • Article (437:1299) A haplotype map of the human genome The International HapMap Consortium D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  6. Review last lecture & New:Genomics D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  7. Genomics - for excellent overview lectures, see these posted by NHGRI & Pevsner: • 1- Genomic sequencing • Mapping and Sequencing CTGA2005Lecture1.pdf • Eric Green, NHGRI • 2- Human genome project • The Human Genome 2005-10-19_ch17.pdf • Jonathan Pevsner, Kennedy Krieger Institute • 3- SNPs • Studying Genetic Variation II: Computational Techniques • Jim Mullikin, NHGRICTGA2005Lecture13.pdf • 4- Comparative Genomics • Comparative Sequence Analysis • Elliott Margulies, NHGRI CTGA2005Lecture8.pdf D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  8. 1- Genomic sequencingMany thanks to:Eric Green, NHGRI for the following slides extracted from his lecture on:Mapping and SequencingCTGA2005Lecture1.pdf D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  9. Genomic Sequencing - Brief Review E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  10. Comparison of Sequenced Genome Sizes E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  11. Comparison of Genetic & Physical Maps E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  12. STSs: Provide common markers for "linking" genetic & physical maps E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  13. With complete genomes (now), why bother to generate physical maps? E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  14. Genomic sequencing requires assembly of sequences obtained from DNA cloned in vectors E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  15. Advances in DNA Sequencing Technology E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  16. Sequencing Method #1: Gilbert-Maxim "Chemical Degradation" E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  17. Sequencing Method #2: Sanger "Di-deoxy Chain Termination" E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  18. Automated Sequencing for Genome Projects: Sanger method - with improvements Another recent improvement: rapid & high resolution separation of fragments in capillaries instead of gels (E Yeung,Ames Lab, ISU) E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  19. Human Genome Sequencing • Two approaches: • Public (government) - International Consortium • (6 countries, NIH-funded in US) • "Hierarchical" cloning & BAC-by-BAC sequencing • Map-based assembly • Private (industry) - Celera (Craig Ventner) • Whole genome random "shotgun" sequencing • Computational assembly • (took advantage of public maps & sequences,too) • Guess which human genome they sequenced? Craig's D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  20. "Hierarchical" BAC-by-BAC Shotgun Sequencing E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  21. Whole-Genome "Shotgun" Sequencing E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  22. "Hierarchical" Subcloning Strategy E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  23. "Shotgun" Sequencing Stategy E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  24. Computational Assembly of Shotgun Sequences E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  25. Either Strategy: Sequence "Finishing" = Hard !! E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  26. 1st Eukaryotic Genome Sequence: S. cerevisiae E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  27. 1st Animal Genome Sequence: C. elegans E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  28. Timetable for Human Genome Sequencing: Faster than expected! E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  29. 1st Draft Human Genome - "Finished" in 2001 E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  30. Public Sequencing - International Consortium E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  31. "Finishing" the Human Genome - continues… E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  32. "Complete" Human Genome Sequence - What next? E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  33. Interpreting the Human Genome Sequence E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  34. Comparative Genomics: now with entire genomic sequences E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  35. Comparing Genomes: Functional Elements E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  36. ENCODE Project E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  37. ENCODE - Web Sites E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  38. Eric Green's Genomic Sequencing Challenges (2005 List) E Green 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  39. 2- Human Genome ProjectMany thanks to:Jonathan Pevsner Kennedy Krieger Institutefor the following slides extracted from his lecture on:The Human Genome2005-10-19_ch17.pdf D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  40. J Pevsner 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  41. Human Genome Sequence - Where is it? J Pevsner 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  42. Human Genome Project: What have we learned? J Pevsner 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  43. Human Genome Project: What have we learned? J Pevsner 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  44. Human Genome Project: What have we learned? J Pevsner 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  45. Human Genome Project: What have we learned? J Pevsner 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  46. Human Genome Project: What have we learned? J Pevsner 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  47. Human Genome Project: What have we learned? J Pevsner 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  48. Human Genome Project: What have we learned? J Pevsner 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  49. Human Genome Project: What have we learned? J Pevsner 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches

  50. Human Genome Project: What have we learned? J Pevsner 2005 D Dobbs ISU - BCB 444/544X: "Omics" - Experimental Approaches