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Overview Introduction Biological network data Text mining Gene Ontology Expression data basics Expression, text mining, and GO Modules and complexes Domains and conclusion Biological Network Data (Getting external stuff) Lecture Cytoscape plugins Protein interactions: types and measurement Protein association: text mining and coexpression Public data repositories Hands-on Installing Cytoscape plugins Filters A few external data resources Cytoscape Plugins available for…. Gene Ontology analysis Domain-level protein network analysis Interface to the Oracle spatial network data model Shortest-Path graph analysis algorithms Interactions Protein-protein interactions Protein-DNA interactions Associations (co-expression, text mining, etc). Protein-protein interactions Source: http://www.biocarta.com/pathfiles/h_caspasePathway.asp Measuring protein-protein interactions: Yeast Two-Hybrid Source: http://www.bioteach.ubc.ca/ Measuring protein-protein interactions Co-immunoprecipitation (Co-IP) Courtesy of Rhoded Sharan, Tel Aviv University Key points on protein interactions High false positive rate High false negative rate Currently, not much overlap between published interaction datasets Most confidence given to observed interactions with other supporting evidence. Protein-DNA interactions From: Molecular Biology of the Cell, Alberts et al., 2002 Measuring Protein-DNA Interactions ChIP-on-chip From: http://www.chiponchip.org/ Key points on protein-DNA interactions There has not been much data historically. With new technology, that is changing rapidly. The technology is still immature, and data interpretation should be done cautiously. Text mining Courtesy of Gary Bader, Memorial Sloan Kettering Cancer Center Conserved co-expression networks From: Genome Biology 2004, 5:R100 Genetic Interactions From: Nature Biotechnology 23, 561 - 566 (2005) Key points on association data An association does not imply an interaction. Compared to protein interaction data Higher false positive rate Often better coverage, lower false negative rate Always remember: interactions are context-dependent! From: de Lichtenberg et al., Science. 2005 Feb 4;307(5710):724-7 Also: Metabolic pathways Public data repositories Protein-protein interaction data BIND, DIP, MINT, MIPS, InACT, … Protein-DNA interaction data BIND, Transfac, … Metabolic pathway data BioCyc, KEGG, WIT, … Text-mining, coexpression Pre-BIND, Tmm, … Pathway data exchange formats: 1. BioPAX (supported by Cytoscape) 2. PSI-MI (supported by Cytoscape) 3. Hundreds of other formats specific to each pathway data repository (not generally supported by Cytoscape) Hands-on session Installing Cytoscape plugins Getting external data Merging networks Using filters