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Modeling the dynamic assembly of cell cycle complexes from high-throughput data

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Lars Juhl Jensen
Lars Juhl Jensen

EMBO Young Investigators Programme, 3rd Symposium, European Molecular Biology Laboratory, Heidelberg, Germany, June 24-26, 2005

Technology
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Lars Juhl Jensen EMBL Heidelberg Modeling the dynamic assembly of cell cycle complexes from high-throughput data
A qualitative model of the yeast cell cycle ,[object Object],[object Object],[object Object],© Chen et al., Mol. Biol. Cell, 2004
Getting the parts list Yeast culture Microarrays Gene expression Expression profile Cho & Spellman et al. 600 periodically expressed genes (with associated peak times) that encode “dynamic proteins” The parts list New analysis
Constructing a reliable protein network ,[object Object],[object Object],[object Object],[object Object]
Extracting a cell cycle interaction network Cell cycle microarray data Physical PPI interactions with confidence scores Expand the set of proteins to include non-periodic proteins that are strongly connected to periodic proteins Raw Data Node selection List of periodically expressed proteins with peak time Interactions Require compatible compartments and high confidence Extract cell cycle network
The temporal interaction network ,[object Object],[object Object]
[object Object],[object Object],Static proteins play a major role
Cdc28p and its interaction partners
Just-in-time synthesis vs. just-in-time assembly ,[object Object],[object Object],[object Object],[object Object]
Assembly of the pre-replication complex
Network as a discovery tools ,[object Object],[object Object],[object Object]
Transcription is linked to phosphorylation ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Is it possible to predict binding affinities? ,[object Object],[object Object],[object Object],[object Object],[object Object]
Conclusions and outlook ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Acknowledgments ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Thank you!

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Modeling the dynamic assembly of cell cycle complexes from high-throughput data

  • 1. Lars Juhl Jensen EMBL Heidelberg Modeling the dynamic assembly of cell cycle complexes from high-throughput data
  • 2.
  • 3. Getting the parts list Yeast culture Microarrays Gene expression Expression profile Cho & Spellman et al. 600 periodically expressed genes (with associated peak times) that encode “dynamic proteins” The parts list New analysis
  • 4.
  • 5. Extracting a cell cycle interaction network Cell cycle microarray data Physical PPI interactions with confidence scores Expand the set of proteins to include non-periodic proteins that are strongly connected to periodic proteins Raw Data Node selection List of periodically expressed proteins with peak time Interactions Require compatible compartments and high confidence Extract cell cycle network
  • 6.
  • 7.
  • 8. Cdc28p and its interaction partners
  • 9.
  • 10. Assembly of the pre-replication complex
  • 11.
  • 12.
  • 13.
  • 14.
  • 15.