integration of diverse large-scale datasets
TRANSCRIPT
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Integration of diverselarge-scale datasets
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Lars Juhl Jensen
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promoter analysis
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Jensen et al., Bioinformatics, 2000
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DNA structure
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genome visualization
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Pedersen et al., Journal of Molecular Biology, 2000
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microarray normalization
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Workman et al., Genome Biology, 2002
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protein function prediction
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STRING
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integrate diverse evidence
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functional interactions
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Bork et al., Current Opinion in Structural Biology, 2005
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179 proteomes
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evolution
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statistics
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(the original sin)
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prokaryotes
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genomic context methods
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gene fusion
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gene neighborhood
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phylogenetic profiles
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Cell
Cellulosomes
Cellulose
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eukaryotes
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integrate diverse datasets
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Jensen et al., Drug Discovery Today: Targets, 2004
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curated knowledge
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MIPSMunich Information center
for Protein Sequences
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KEGGKyoto Encyclopedia of Genes and Genomes
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STKESignal Transduction Knowledge Environment
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Reactome
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literature mining
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MEDLINE
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SGDSaccharomyces Genome Database
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The Interactive Fly
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OMIMOnline Mendelian Inheritance in Man
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co-mentioning
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NLPNatural Language Processing
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Gene and protein namesCue words for entity recognitionVerbs for relation extraction
[nxgene The GAL4 gene]
[nxexpr The expression of [nxgene the cytochrome genes [nxpg CYC1 and CYC7]]]is controlled by[nxpg HAP1]
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primary experimental data
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microarray expression data
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GEOGene Expression Omnibus
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physical protein interactions
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BINDBiomolecular Interaction Network Database
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MINTMolecular Interactions Database
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GRIDGeneral Repository for Interaction Datasets
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DIPDatabase of Interacting Proteins
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HPRDHuman Protein Reference Database
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problems
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many sources
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(different gene identifiers)
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many types of evidence
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questionable quality
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not directly comparable
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spread over many species
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huge synonyms lists
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calculate raw quality scores
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calibrate vs. gold standard
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KEGGKyoto Encyclopedia of Genes and Genomes
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von Mering et al., Nucleic Acids Research, 2005
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transfer based on orthology
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combine all evidence
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Bork et al., Current Opinion in Structural Biology, 2005
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cell cycle
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qualitative modeling
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Chen et al., Molecular Biology of the Cell, 2004
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Chen et al., Molecular Biology of the Cell, 2004
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synchronized cell culture
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microarray time series
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periodically expressed genes
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S. cerevisiae
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Cho et al.
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Spellman et al.
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numerous analysis methods
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Cho et al.
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Spellman et al.
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Zhao et al.
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Johansson et al.
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Luan and Li
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Lu et al.
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Ahdesmäki et al.
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Willbrand et al.
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no benchmarking
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de Lichtenberg et al., Bioinformatics, 2005
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reproducibility
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de Lichtenberg et al., Bioinformatics, 2005
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regulation vs. periodicity
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de Lichtenberg et al., Bioinformatics, 2005
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list of 600 periodic genes
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S. pombe
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several expression studies
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reproducibility
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Marguerat et al., Yeast, 2006
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name inconsistencies
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Marguerat et al., Yeast, 2006
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different analysis methods
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no benchmarking
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Marguerat et al., Yeast, 2006
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Marguerat et al., Yeast, 2006
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too many genes suggested
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Marguerat et al., Yeast, 2006
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Marguerat et al., Yeast, 2006
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averaging better than voting
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Marguerat et al., Yeast, 2006
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S. cerevisiae
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list of 600 periodic genes
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protein interaction data
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von Mering et al., Nucleic Acids Research, 2005
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de Lichtenberg et al., Science, 2005
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dynamic proteins
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static proteins
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de Lichtenberg et al., Science, 2005
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reproduces what is known
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de Lichtenberg et al., Science, 2005
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many detailed predictions
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de Lichtenberg et al., Science, 2005
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global trends
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dynamic proteins
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de Lichtenberg et al., Science, 2005
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static proteins
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de Lichtenberg et al., Science, 2005
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just-in-time assembly
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de Lichtenberg et al., Science, 2005
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de Lichtenberg et al., Science, 2005
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coordinated regulation
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periodically expressed genes
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Cdc28p substrates
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PEST degradation signals
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the human interactome
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yeast two-hybrid
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1936
13
4
4
1385
65
18465
Stelzl et al. Rual et al.
Small-scale studies
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32
0
3
4
18
4
23
Stelzl et al. Rual et al.
Small-scale studies
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62 8 39
Small-scale studies
Stelzl et al. Rual et al.
852
17
473
432
69
260
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3.5% and 21% sensitivity
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in a couple of years
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the human interactome
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100% = 1/5?
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the yeast interactome
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five years ago
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yeast two-hybrid
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1150
117
117
72
4053
118
4469
Uetz et al. Ito et al.
Small-scale studies
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162
53
34
72
180
29
338
Uetz et al. Ito et al.
Small-scale studies
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511 189 616
Small-scale studies
Uetz et al. Ito et al.
439
178
759
897
190
1347
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19% and 12% sensitivity
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the challenge
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how to get from here …
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1936
13
4
4
1385
65
18465
Stelzl et al. Rual et al.
Small-scale studies
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… to there …
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de Lichtenberg et al., Science, 2005
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Acknowledgments
• The STRING team (EMBL)– Christian von Mering– Berend Snel– Martijn Huynen– Sean Hooper– Mathilde Foglierini– Julien Lagarde– Peer Bork
• Literature mining project(EML Research)– Jasmin Saric– Rossitza Ouzounova– Isabel Rojas
• Cell cycle studies (CBS)– Ulrik de Lichtenberg– Thomas Skøt Jensen– Søren Brunak
• S. pombe cell cycle (Sanger)– Samuel Marguerat– Jürg Bähler
• Inspiration for presentation– Lawrence Lessig– Dick Clarence Hardt– Anders Gorm Pedersen
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Thank you!