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Gene Ontology (GO) Project geneontology/ Jane Lomax

Gene Ontology (GO) Project http://www.geneontology.org/ Jane Lomax There is a lot of biological research output You’re interested in which genes control in mesoderm development… You get 6752 results! How will you ever find what you want? time Defense response Immune response

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Gene Ontology (GO) Project geneontology/ Jane Lomax

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  1. Gene Ontology (GO) Project http://www.geneontology.org/ Jane Lomax

  2. There is a lot of biological research output

  3. You’re interested in which genes control inmesoderm development…

  4. You get 6752 results! How will you ever find what you want?

  5. time Defense response Immune response Response to stimulus Toll regulated genes JAK-STAT regulated genes Puparial adhesion Molting cycle hemocyanin Amino acid catabolism Lipid metobolism Peptidase activity Protein catabloism Immune response Immune response Toll regulated genes control attacked Microarray data shows changed expression of thousands of genes. How will you spot the patterns? Bregje Wertheim at the Centre for Evolutionary Genomics, Department of Biology, UCL and Eugene Schuster Group, EBI.

  6. Scientists work hard

  7. There are lots of papers to read http://www.teamtechnology.co.uk/f-scientist.jpg

  8. More papers… http://www.teamtechnology.co.uk/f-scientist.jpg

  9. more and more and more… http://www.teamtechnology.co.uk/f-scientist.jpg

  10. Help! more and more and more! http://www.teamtechnology.co.uk/f-scientist.jpg

  11. The Gene Ontology provides a way to capture and represent biological all this knowledge in a computable form

  12. The Gene Ontology

  13. GO browser

  14. Search on ‘mesoderm development’ mesoderm development

  15. Definition of mesoderm development Gene products involved in mesoderm development

  16. GO can be used to help analyse microarray data

  17. Microarray process: • Treat samples • Collect mRNA • Label • Hybridize • Scan • Normalize • Select differentially regulated genes • Understand the biological phenomena involved

  18. Traditional analysis • gene by gene basis • requires literature searching • time-consuming

  19. Gene 1 Apoptosis Cell-cell signaling Protein phosphorylation Mitosis … Gene 2 Growth control Mitosis Oncogenesis Protein phosphorylation … Gene 3 Growth control Mitosis Oncogenesis Protein phosphorylation … Gene 4 Nervous system Pregnancy Oncogenesis Mitosis … Gene 100 Positive ctrl. of cell prolif Mitosis Oncogenesis Glucose transport … Traditional analysis

  20. GO:0006915 : apoptosis Using GO annotations • But by using GO annotations, this work has already been done

  21. Grouping by process Mitosis Gene 2 Gene 5 Gene45 Gene 7 Gene 35 … Glucose transport Gene 7 Gene 3 Gene 6 … Apoptosis Gene 1 Gene 53 Positive ctrl. of cell prolif. Gene 7 Gene 3 Gene 12 … Growth Gene 5 Gene 2 Gene 6 …

  22. GO for microarray analysis • Annotations give ‘function’ label to genes • Ask meaningful questions of microarray data e.g. • genes involved in the same process, same/different expression patterns?

  23. How does the Gene Ontology work?

  24. GO structure • GO isn’t just a flat list of biological terms • terms are related within a hierarchy

  25. gene A GO structure

  26. GO structure • This means genes can be grouped according to user-defined levels • Allows broad overview of gene set or genome

  27. How does GO work? What information might we want to capture about a gene product?

  28. How does GO work? What information might we want to capture about a gene product? • What does the gene product do?

  29. How does GO work? What information might we want to capture about a gene product? • What does the gene product do? • Where and when does it act?

  30. How does GO work? What information might we want to capture about a gene product? • What does the gene product do? • Where and when does it act? • Why does it perform these activities?

  31. GO structure • GO terms divided into three parts: • cellular component • molecular function • biological process

  32. Cellular Component • where a gene product acts

  33. Cellular Component

  34. Cellular Component

  35. Cellular Component • Enzyme complexes in the component ontology refer to places, not activities.

  36. Molecular Function • activities or “jobs” of a gene product glucose-6-phosphate isomerase activity

  37. Molecular Function insulin binding insulin receptor activity

  38. Molecular Function drug transporter activity

  39. Molecular Function • A gene product may have several functions; a function term refers to a reaction or activity, not a gene product • Sets of functions make up a biological process

  40. cell division Biological Process a commonly recognized series of events

  41. Biological Process transcription

  42. Biological Process regulation of gluconeogenesis

  43. Biological Process limb development

  44. Biological Process courtship behavior

  45. Ontology Structure • Terms are linked by two relationships • is-a  • part-of 

  46. cell membrane chloroplast mitochondrial chloroplast membrane membrane is-a part-of Ontology Structure

  47. Ontology Structure • Ontologies are structured as a hierarchical directed acyclic graph (DAG) • Terms can have more than one parent and zero, one or more children

  48. Ontology Structure cell membrane chloroplast mitochondrial chloroplast membrane membrane Directed Acyclic Graph (DAG) - multiple parentage allowed

  49. Anatomy of a GO term unique GO ID id: GO:0006094 name: gluconeogenesis namespace: process def: The formation of glucose from noncarbohydrate precursors, such as pyruvate, amino acids and glycerol. [http://cancerweb.ncl.ac.uk/omd/index.html] exact_synonym: glucose biosynthesis xref_analog: MetaCyc:GLUCONEO-PWY is_a: GO:0006006 is_a: GO:0006092 term name ontology definition synonym database ref parentage

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