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Protein interactions Lars Juhl Jensen what is an interaction? physical interaction functional association fuzzy definitions physical interactions stable interactions transient interactions binary interactions multimeric complexes Jensen et al., Drug Discovery Today: TARGETS, 2004 spoke representation Jensen et al., Drug Discovery Today: TARGETS, 2004 matrix representation Jensen et al., Drug Discovery Today: TARGETS, 2004 interaction assays yeast two-hybrid fragment complementation affinity purification Jensen & Bork, Science, 2008 interaction databases BioGRID General Repository for Interaction Datasets DIP Database of Interacting Proteins IntAct MINT Molecular Interactions Database Exercise 1 Go to http://thebiogrid.org Query for human TYMS Find the interaction partners Check their sources Think of possible problems possibly many errors only high-throughput one assay one study functional associations guilt by association STRING Franceschini et al., Nucleic Acids Research, 2013 Exercise 2 Go to http://string-db.org Query for human TYMS Show only highest confidence Show network in confidence view Show network in evidence view genomic context operons Korbel et al., Nature Biotechnology, 2004 bidirectional promoters Korbel et al., Nature Biotechnology, 2004 gene fusion Korbel et al., Nature Biotechnology, 2004 phylogenetic profiles Korbel et al., Nature Biotechnology, 2004 a real example Cell Cellulosomes Cellulose experimental data physical interactions Jensen & Bork, Science, 2008 genetic interactions Beyer et al., Nature Reviews Genetics, 2007 gene coexpression text mining co-mentioning curated knowledge complexes pathways Letunic & Bork, Trends in Biochemical Sciences, 2008 many databases different formats different identifiers variable quality not comparable not same species hard work (graduate students) quality scores von Mering et al., Nucleic Acids Research, 2005 calibrate vs. gold standard von Mering et al., Nucleic Acids Research, 2005 homology-based transfer orthologs vs. paralogs Franceschini et al., Nucleic Acids Research, 2013 Exercise 3 Query STRING for human TYMS Show only experimental evidence Show up to 50 interaction partners Show also low-confidence links Redo exercise for mouse TYMS related web resources STITCH STRING + 300k chemicals drugs metabolites known drug targets high-throughput screens metabolic pathways Exercise 4 Go to http://stitch-db.org Query for human TYMS What is the role of thymidylate? What is the role of dUMP? What is the role of Permetrexed? general approach suite of new resources COMPARTMENTS TISSUES DISEASES curated knowledge experimental data text mining computational predictions common identifiers quality scores visualization compartments.jensenlab.org tissues.jensenlab.org thank you!
