Mining heterogeneous data: Understanding systems at the level of complexes and networks

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Mining heterogeneous data Understanding systems at the level of complexes and networks Lars Juhl Jensen

Transcript of Mining heterogeneous data: Understanding systems at the level of complexes and networks

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Mining heterogeneous dataUnderstanding systems at the level of complexes and networks

Lars Juhl Jensen

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the cell cycle

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grow and divide

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one cell

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two cells

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four phases

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G1 phase

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growth

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S phase

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DNA replication

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G2 phase

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growth

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M phase

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cell division

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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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scoring scheme

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shape

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magnitude

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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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S. cerevisiae

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Jensen & Bork, Science, 2008

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high error rate

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scoring scheme

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von Mering et al., Nucleic Acids Research, 2005

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calibrate against KEGG

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quality threshold

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temporal network

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time of peak mRNA level

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time of protein synthesis

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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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evolution

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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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reanalysis

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cycling genes

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same algorithm

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cross-species comparison

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orthologous genes

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sequence similarity

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

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protein complexes

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DNA polymerases

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

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all cell-cycle complexes

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

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time of peak mRNA level

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time of action

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just-in-time assembly

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generalize to metabolism

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linear pathways

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deoxynucleotide synthesis

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just-in-time flux

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cell-cycle phenotypes

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H. sapiens

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siRNA screen

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comparison with expression

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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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bias

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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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layers of regulation

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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 insights

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Acknowledgments

Thomas Skøt JensenUlrik de Lichtenberg

Søren BrunakPeer Bork

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larsjuhljensen

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