systems biology: large-scale biomedical data mining

Systems biologyLarge-scale biomedical data mining

Lars Juhl Jensen

Phase 1association networks

who?

protein networks

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

genomic context

gene fusion

Korbel et al., Nature Biotechnology, 2004

conserved neighborhood

Korbel et al., Nature Biotechnology, 2004

phylogenetic profiles

Korbel et al., Nature Biotechnology, 2004

gene coexpression

protein interactions

Jensen & Bork, Science, 2008

genetic interactions

Beyer et al., Nature Reviews Genetics, 2007

curated knowledge

Letunic & Bork, Trends in Biochemical Sciences, 2008

>10 km

text mining

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

co-mentioning

NLPNatural Language Processing

different formats

different names

variable quality

not comparable

spread over 630 genomes

confidence scores

von Mering et al., Nucleic Acids Research, 2005

transfer by orthology

von Mering et al., Nucleic Acids Research, 2005

Frishman et al., Modern Genome Annotation, 2009

Phase 2signaling networks

what?

phosphoproteomics

kinases are unknown

sequence motifs

machine-learning methods

Miller, Jensen et al., Science Signaling, 2008

peptide assays

Miller, Jensen et al., Science Signaling, 2008

automated pipeline

Miller, Jensen et al., Science Signaling, 2008

sequence specificity

no context

network context

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

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

>2x better accuracy

context is crucial

example

DNA damage response

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

small-scale validation

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

Phase 3dynamic networks

when?

cell-cycle regulation

microarray time courses

Gauthier et al., Nucleic Acids Research, 2007

protein interactions

temporal network

de Lichtenberg, Jensen et al., Science, 2005

de Lichtenberg, Jensen et al., Science, 2005

just-in-time assembly

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

evolutionary flexibility

individual genes

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

protein complexes

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

phosphorylation

co-evolution

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

summary

data mining

specific predictions

systems properties

thank you!

AcknowledgmentsNetPhorest.info

– Rune Linding– Martin Lee Miller– Francesca Diella– Claus Jørgensen– Michele Tinti– Lei Li– Marilyn Hsiung– Sirlester A. Parker– Jennifer Bordeaux– Thomas Sicheritz-Pontén– Marina Olhovsky– Adrian Pasculescu– Jes Alexander– Stefan Knapp– Nikolaj Blom– Peer Bork– Shawn Li– Gianni Cesareni– Tony Pawson– Benjamin E. Turk– Michael B. Yaffe– Søren Brunak

STRING-DB.org– Christian von Mering– Damian Szklarczyk– Michael Kuhn– Manuel Stark– Samuel Chaffron– Chris Creevey– Jean Muller– Tobias Doerks– Philippe Julien– Alexander Roth– Milan Simonovic– Jan Korbel– Berend Snel– Martijn Huynen– Peer Bork

Reflect.ws– Sune Frankild– Heiko Horn– Evangelos Pafilis– Michael Kuhn– Nigel Brown– Reinhardt Schneider– Sean O’Donoghue

NetworKIN.info– Rune Linding– Heiko Horn– Gerard Ostheimer– Martin Lee Miller– Francesca Diella– Karen Colwill– Jing Jin– Pavel Metalnikov– Vivian Nguyen– Adrian Pasculescu– Jin Gyoon Park– Leona D. Samson– Rob Russell– Peer Bork– Michael Yaffe– Tony Pawson

Cyclebase.org– Ulrik de Lichtenberg– Thomas Skøt Jensen– Nicholas Paul Gauthier– Rasmus Wernersson– Søren Brunak

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