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Nikolaj Blom Center for Biological Sequence Analysis BioCentrum-DTU

”Resources of Biomolecular Data: Sequences, Structures and Functionality” PhD course #27803. Nikolaj Blom Center for Biological Sequence Analysis BioCentrum-DTU Technical University of Denmark nikob @cbs.dtu.dk. Outline. Magnitudes and Scales Resources: Data Sources & Tools

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Nikolaj Blom Center for Biological Sequence Analysis BioCentrum-DTU

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  1. ”Resources of Biomolecular Data: Sequences, Structures and Functionality” PhD course #27803 Nikolaj Blom Center for Biological Sequence Analysis BioCentrum-DTU Technical University of Denmark nikob@cbs.dtu.dk

  2. Outline • Magnitudes and Scales • Resources: Data Sources & Tools • Primary DNA sources • Sequence Repositories • Structure Repositories • Functional Categorization • Integration of Databases • The Human Genome • Genome Browsers • Prediction Tools • Evaluation of Prediction Servers • Starting points • Link collections

  3. Learning Objectives • The student should be able to: • Describe differences between sequence repositories and curated databases • Describe the challenges of maintaining genome-wide biological databases • List two entry points for getting an overview of ”my gene of interest” • Describe how prediction servers may be evaluated

  4. Resources: Sources & Tools • There is A LOT OF biomolecular databases/sources • A LOT OF overlap of information/redundancy • A LOT OF TOOLS • Personal picks/preferences • User-friendliness • Update intervals • Curation efforts / error correction • Linkage to other DBs

  5. Faster than Moore’s law...

  6. Faster than Moore’s law...

  7. Human Genome Published HUGO: Nature, 15.feb.2001 Celera: Science, 16.feb.2001

  8. Magnitudes and Scales • Human genome 3,200,000,000 bp • Single basepair  full genome is 9 orders of magnitude • Genome = Football field: ~3 billion leaves of grass • Single base A T G C (or SNP) =1 leaf of grass • Genome browsing • Zooming from whole stadium to single leaf

  9. How we got the sequence • Sanger chain termination method

  10. Primary DNA sources • Trace files repositories • Single read: 500-1000 bp (~golf ball size/ jig saw puzzle) • Variable quality • WashU-Merck Human EST Project / Trace files • ”Base-calling” non-trivial G, C or nothing?

  11. Assembly is Non-trivial!

  12. Sequence repositories - GenBank et al. • GenBank / EMBL / DDBJ • Highly redundant (many versions of same gene) • Cross-updated daily • Version history is recorded • Previous sequence records can be retrieved • Contigs/HTGS (100-200 kb) finishing at different stages • DraftFinished • Includes genomic DNA, cDNA, ESTs, translated peptides

  13. Non-redundant and Curated databases • Non-redundant • Manual or automatic curation • DNA • RefSeq (NCBI; semi-automated) • Ensembl gene index (automated) • Protein • RefSeq (NCBI; semi-automated) • TrEMBL (EMBL; automated)

  14. Curated database: UniProt/SwissProt • SIB - Swiss Institute of Bioinformatics • Protein Knowledgebase / Sequence Database • Highly curated • Experimental evidence evaluated (e.g. modifications) • All 80,000 entries checked by Amos Bairoch himself ;-) • ExPASy - Expert Protein Analysis System • Proteomics tools: links + local servers

  15. Structure databases / Protein Data Bank (PDB) • X-ray , NMR biomolecular structures • Protein Data Bank (PDB) • http://www.rcsb.org/pdb/

  16. Structure databases / Protein Data Bank (PDB)

  17. Functional Categorization • Gene Ontology (GO) • Hierarchical • Controlled vocabulary

  18. Functional Categorization • Gene Ontology (GO) http://www.geneontology.org/ • Molecular Function - the tasks performed by individual gene products; examples are transcription factor and DNA helicase • Biological Process - broad biological goals, such as mitosis or purine metabolism, that are accomplished by ordered assemblies of molecular functions • Cellular Component - subcellular structures, locations, and macromolecular complexes; examples include nucleus, telomere, and origin recognition complex

  19. Integration of databases - Webs of web-sites • Links, links, links... • SRS = Sequence Retrieval System • Powerful, complex query language • BioDAS – Distributed Annotation System http://srs.ebi.ac.uk/

  20. For ’my gene’, how do I: • Get an overview of the sequence information known? (GeneCards+OMIM) • Examine the ’Genome Neighbourhood’? (Genome Browsers) • Predict protein post-translational modifications (PTMs)? (Prediction servers) • (Evaluate the value of predicted features)

  21. GeneCards http://nciarray.nci.nih.gov/cards/

  22. GeneCards-II

  23. GeneCards-III

  24. GeneCards-IV

  25. GeneCards-V

  26. Genetic/Medical Information • OMIM, Online Mendelian Inheritance in Man (NCBI) • The OMIM database is a catalog of human genes and genetic disorders • >16,000 entries (April, 2006) • Examples: cystic fibrosis, prions, amyloid precursor protein • Condensed, highly curated descriptions of genetics/disease/animal models/references

  27. OMIM-I (http://www3.ncbi.nlm.nih.gov/Omim/)

  28. OMIM-II

  29. OMIM-III

  30. For ’my gene’, how do I: • Get an overview of the sequence information known? (GeneCards+OMIM) • Examine the ’Genome Neighbourhood’? (Genome Browsers) • Predict protein post-translational modifications (PTMs)? (Prediction servers) • (Evaluate the value of predicted features)

  31. Genome Browsing • Three public • Open access • Use same genome build/assembly • NCBI (U.S.) • UCSC (Santa Cruz, U.S.) • EnsEmbl (EBI, EU) • (One private) • (Restricted, commercial; closed 2005)

  32. Celera Discovery System & Database

  33. Genome Browsers - Portals to the Genomic World • UCSC – Univ. California – Santa Cruz (U.S.) • http://genome.ucsc.edu/ • NCBI – National Center for Biotechnology Information (U.S.) • http://www.ncbi.nlm.nih.gov/Genomes/index.html • EnsEmbl – European Molecular Biology Laboratory (E.U.) • http://www.ensembl.org/

  34. UCSC – Genome Browser

  35. UCSC – Genome Browser II

  36. NCBI

  37. NCBI

  38. EnsEmbl – Genome Browser

  39. EnsEmbl – Genome Browser

  40. EnsEmbl – Genome Browser

  41. EnsEmbl – Genome Browser

  42. EnsEmbl – Genome Browser

  43. EnsEmbl – Genome Browser

  44. For ’my gene’, how do I: • Get an overview of the sequence information known? (GeneCards) • Examine the ’Genome Neighbourhood’? (Genome Browsers) • Predict protein post-translational modifications (PTMs) or Gene Structure? (Prediction servers) • ...and evaluate the reliability of prediction methods

  45. CBS Services/Toolbox http://www.cbs.dtu.dk/services/

  46. NetPhos – a prediction server http://www.cbs.dtu.dk/services/NetPhos/

  47. NetPhos – a prediction server

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