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Functional profiling of the S. cerevisiae genome

Functional profiling of the S. cerevisiae genome. Exploring genetic interactions and networks with yeast Charlie Boone et al. G Giaever, et al. What is the question of Giaever’s paper? What are they looking at? Why is this genomics instead of genetics? What is Boone’s review about?.

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Functional profiling of the S. cerevisiae genome

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  1. Functional profiling of the S. cerevisiae genome Exploring genetic interactions and networks with yeast Charlie Boone et al G Giaever, et al

  2. What is the question of Giaever’s paper? • What are they looking at? • Why is this genomics instead of genetics? • What is Boone’s review about?

  3. What are the advantages of knocking out all genes compared with a classical genetics approach? • Mutant phenotype reflects a deletion, i.e. complete loss of function • This is “reverse genetics” – so you know the gene that is affected ahead of time • In contrast to random mutagenesis, mutant “saturation” of the genome is assured.

  4. What are the important components of this deletion cassette?

  5. Using the entire library at once From Boone, Exploring genetic networks

  6. First results • Deleted 5916 genes (96.5% of those attempted) • 1105 (18.7%) were essential (only 57% of these known before) • 17% of non-essential ORFs encoded new proteins • 82% of essential genes had human homologs

  7. What would you conclude from this?

  8. Where’s the data? • http://genomics.lbl.gov/YeastFitnessData • 15% show slow growth in YPD at 30oC. • There is a continuous range of growth defects 12% to 90% of wt

  9. What is the question? What are the conclusions? What is the relationship between expression under a particular condition and fitness of a deletion mutant under that condition? Fitness effects do not correlate with extremes in gene expression.

  10. Observe and Pay Attention They found 673 genes (15%) involved in morphology. These were grouped into 7 classes. Clumped and elongated – enriched for cell growth, division, and DNA synthesis. Round – enriched for protein synthesis genes and defective for bud site selection.

  11. What else can we think of doing? Functional profiling has been cited 1,272 times

  12. What did Guri do this year?

  13. Mitochondrial mutants are often important in human disease – how would you use the deletion set to find these?

  14. Andreas Wagner – using these datasets to understand living systems

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