just-in-time assembly: transcriptional and post-translational cell-cycle regulation of protein...
DESCRIPTION
Centre for Computational and Systems Biology (CoSBi), Trento, Italy, January 12, 2010.TRANSCRIPT
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Just-in-time assemblyTranscriptional and post-translational
cell-cycle regulation of protein complexes
Lars Juhl Jensen
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sequence analysis
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Jensen & Knudsen, Bioinformatics, 2000
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Jensen, Gupta et al., Journal of Molecular Biology, 2002
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data integration
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Jensen, Kuhn et al., Nucleic Acids Research, 2009
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Jensen & Bork, Science, 2008
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Campillos, Kuhn et al., Science, 2008
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signaling networks
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Linding, Jensen, Ostheimer et al., Cell, 2007
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text mining
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Pafilis, O’Donoghue, Jensen et al., Nature Biotechnology, 2009
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the cell cycle
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complex process
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one cell
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two cells
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regulation
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gene expression
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protein complexes
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phosphorylation
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targeted degradation
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gene expression
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cell cultures
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S. cerevisiae
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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
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renormalization
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reanalysis
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new scoring scheme
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benchmarking
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Gauthier et al., Nucleic Acids Research, 2007
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protein complexes
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interaction data
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temporal network
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de Lichtenberg, Jensen et al., Science, 2005
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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
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how can we test it?
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evolutionary flexibility
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reanalysis
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microarray time courses
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S. pombe
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H. sapiens
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A. thaliana
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cycling genes
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orthologous genes
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Jensen, Jensen, de Lichtenberg et al., Nature, 2006
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protein complexes
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Jensen, Jensen, de Lichtenberg et al., Nature, 2006
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phosphorylation
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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
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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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co-evolution
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transcriptional regulation
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posttranslational regulation
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phosphoproteomics
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SILAC study of HeLa cells
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multi-block strategy
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Olsen, Vermeulen et al., Science Signaling, 2010
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cycling proteins
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Olsen, Vermeulen et al., Science Signaling, 2010
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regulation of kinases
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Olsen, Vermeulen et al., Science Signaling, 2010
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regulation by kinases
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Olsen, Vermeulen et al., Science Signaling, 2010
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evolution of cycles
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other periodic processes
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microarray time courses
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ultradian cycle
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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
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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
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larsjuhljensen