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Dynamic complex formation during the yeast cell cycle

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Lars Juhl Jensen
Lars Juhl Jensen

EMBL white seminar, European Molecular Biology Laboratory, Heidelberg, Germany, February 4, 2005

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Lars Juhl Jensen EMBL Heidelberg Dynamic complex formation during the yeast cell cycle
A qualitative model of the yeast cell cycle ,[object Object],[object Object],© Chen et al., Mol. Biol. Cell, 2004
Model generation through data integration Model generation A Parts List ,[object Object],[object Object],Dynamic data ,[object Object],[object Object],[object Object],[object Object],Connections YER001W YBR088C YOL007C YPL127C YNR009W YDR224C YDL003W YBL003C YDR225W YBR010W YKR013W … YDR097C YBR089W YBR054W YMR215W YBR071W YBL002W YGR189C YNL031C YNL030W YNL283C YGR152C …
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
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
Topology based quality scores ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Filtering by subcellular localization ,[object Object],[object Object],[object Object],[object Object]
Benchmark of published interaction sets against the MIPS curated yeast complexes ,[object Object],[object Object]
A temporal interaction network ,[object Object],[object Object],G 1 S M G 2
Relaxing the temporal interaction network
The temporal interaction network ,[object Object],[object Object],[object Object],[object Object]
Static proteins play a major role ,[object Object],[object Object]
Cdc28p and its interaction partners
Pho85p and associated cyclins ,[object Object],[object Object],[object Object]
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]
Nucleosome / bud formation module
Rediscovering the “party” hubs and “date” hubs “ Date” hubs: the hub protein interacts with different proteins at different times. “ Party” hubs: the hub protein and its interactors are expressed close in time.
Transcription is linked to phosphorylation ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Conclusions ,[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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Dynamic complex formation during the yeast cell cycle

  • 1. Lars Juhl Jensen EMBL Heidelberg Dynamic complex formation during the yeast cell cycle
  • 2.
  • 3.
  • 4. 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
  • 5. 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
  • 6.
  • 7.
  • 8.
  • 9.
  • 10. Relaxing the temporal interaction network
  • 11.
  • 12.
  • 13. Cdc28p and its interaction partners
  • 14.
  • 15.
  • 16. Assembly of the pre-replication complex
  • 17.
  • 18. Nucleosome / bud formation module
  • 19. Rediscovering the “party” hubs and “date” hubs “ Date” hubs: the hub protein interacts with different proteins at different times. “ Party” hubs: the hub protein and its interactors are expressed close in time.
  • 20.
  • 21.
  • 22.