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Just-in-time assembly Transcriptional and post- translational cell-cycle regulation of protein complexes Lars Juhl Jensen

Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

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Centre for Computational and Systems Biology (CoSBi), Trento, Italy, January 12, 2010.

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Page 1: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

Just-in-time assemblyTranscriptional and post-translational

cell-cycle regulation of protein complexes

Lars Juhl Jensen

Page 2: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes
Page 3: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

sequence analysis

Page 4: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

Jensen & Knudsen, Bioinformatics, 2000

Page 5: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

Jensen, Gupta et al., Journal of Molecular Biology, 2002

Page 6: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes
Page 7: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

data integration

Page 8: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

Jensen, Kuhn et al., Nucleic Acids Research, 2009

Page 9: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

Jensen & Bork, Science, 2008

Page 10: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

Campillos, Kuhn et al., Science, 2008

Page 11: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes
Page 12: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

signaling networks

Page 13: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

Linding, Jensen, Ostheimer et al., Cell, 2007

Page 14: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

text mining

Page 15: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

Pafilis, O’Donoghue, Jensen et al., Nature Biotechnology, 2009

Page 16: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

the cell cycle

Page 17: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

complex process

Page 18: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

one cell

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two cells

Page 20: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes
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regulation

Page 22: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

gene expression

Page 23: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

protein complexes

Page 24: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

phosphorylation

Page 25: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

targeted degradation

Page 26: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

gene expression

Page 27: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

cell cultures

Page 28: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

S. cerevisiae

Page 29: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes
Page 30: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

synchronization

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microarrays

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time courses

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Gauthier et al., Nucleic Acids Research, 2007

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cycling genes

Page 36: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

renormalization

Page 37: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

reanalysis

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new scoring scheme

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benchmarking

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Gauthier et al., Nucleic Acids Research, 2007

Page 41: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

protein complexes

Page 42: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

interaction data

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temporal network

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de Lichtenberg, Jensen et al., Science, 2005

Page 45: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

de Lichtenberg, Jensen et al., Science, 2005

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hypothesis

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just-in-time assembly

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de Lichtenberg, Jensen et al., Cell Cycle, 2007

Page 49: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

how can we test it?

Page 50: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

evolutionary flexibility

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reanalysis

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microarray time courses

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S. pombe

Page 54: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

H. sapiens

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A. thaliana

Page 56: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

cycling genes

Page 57: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

orthologous genes

Page 58: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

Jensen, Jensen, de Lichtenberg et al., Nature, 2006

Page 59: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

protein complexes

Page 60: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

Jensen, Jensen, de Lichtenberg et al., Nature, 2006

Page 61: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

phosphorylation

Page 62: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes
Page 63: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

CDK substrate

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low-throughput data

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high-throughput data

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NetPhosK

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correlation

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Jensen, Jensen, de Lichtenberg et al., Nature, 2006

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Jensen, Jensen, de Lichtenberg et al., Nature, 2006

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correlated changes

Page 71: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

Jensen, Jensen, de Lichtenberg et al., Nature, 2006

Page 72: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

Jensen, Jensen, de Lichtenberg et al., Nature, 2006

Page 73: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

co-evolution

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transcriptional regulation

Page 75: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

posttranslational regulation

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phosphoproteomics

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SILAC study of HeLa cells

Page 78: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

multi-block strategy

Page 79: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

Olsen, Vermeulen et al., Science Signaling, 2010

Page 80: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

cycling proteins

Page 81: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

Olsen, Vermeulen et al., Science Signaling, 2010

Page 82: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

regulation of kinases

Page 83: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

Olsen, Vermeulen et al., Science Signaling, 2010

Page 84: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

regulation by kinases

Page 85: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

Olsen, Vermeulen et al., Science Signaling, 2010

Page 86: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

evolution of cycles

Page 87: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

other periodic processes

Page 88: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

microarray time courses

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ultradian cycle

Page 90: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

S. cerevisiae

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Trachana, Jensen & Bork, EMBO Reports, 2010

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diurnal cycle

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A. thaliana

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Trachana, Jensen & Bork, EMBO Reports, 2010

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mammals

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Trachana, Jensen & Bork, EMBO Reports, 2010

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paralogous genes

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same cellular functions

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different periodic processes

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three independent lineages

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summary

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reanalysis

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integration

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high-throughput data

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biological discoveries

Page 106: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

Acknowledgments

• Just-in-time assembly– Ulrik de Lichtenberg– Thomas Skøt Jensen– Søren Brunak– Peer Bork

• Comparison with othercycling processes– Kalliopi Trachana– Peer Bork

• Proteomics– Jesper V. Olsen– Michiel Vermeulen– Anna Santamaria– Chanchal Kumar– Martin Lee Miller– Florian Gnad– Jürgen Cox– Thomas Skøt Jensen– Erich A. Nigg– Søren Brunak– Matthias Mann

Page 107: Just-in-time assembly: Transcriptional and post-translational cell-cycle regulation of protein complexes

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