Network & Systems Modeling 29 June 2009 NCSU GO Workshop
GO Enrichment: the structure of the GO allows its to be queried in a hierarchical manner. use the GO DAG Structure to cluster differentially expressed gene sets determine which GO terms are statistically over- represented in the set Systems biology: study of complex interactions in biological systems integrates data from multiple experimental types develop networks describing interactions within the system GO Enrichment & Systems Biology
GO Enrichment Analysis DAVID: GOStat: EasyGO: AmiGO bin/amigo/term_enrichment (does not use IEA) bin/amigo/term_enrichment Onto-Express & OE2GO GOEAST Comparison of enrichment analysis tools : Nucleic Acids Research, 2009, Vol. 37, No. 1 1–13 (Tool_Comparison_09.pdf)
Database for Annotation, Visualization and Integrated Discovery
Species represented in Onto-Express For uploading your own annotations use OE2GO
Comparison Onto-Express, EasyGO, GOstat and DAVID Test set: 60 randomly selected chicken genes Used AgBase GO annotations as baseline annotations Vandenberg et al (BMC Bioinformatics, in review)
Systems Biology Models interactions of components in the system (dynamic). Nanduri B. and McCarthy F.M. (2007). "AgBase - a tool for systems biology in agricultural species." CAB Reviews: Perspectives in Agriculture, Veterinary Science, Nutrition and Natural Resources, 2(078):13-26.
Systems Biology Workflow Nanduri & McCarthy CAB reviews, 2008
Pathways & Networks A network is a collection of interactions Pathways are a subset of networks Network of interacting proteins that carry out biological functions such as metabolism and signal transduction All pathways are networks of interactions NOT ALL NETWORKS ARE PATHWAYS
Biological Networks Networks often represented as graphs Nodes represent proteins or genes that code for proteins Edges represent the functional links between nodes (ex regulation) Small changes in graph’s topology/architecture can result in the emergence of novel properties
Nature 411, 2001, H. Jeong, et al Yeast Protein-Protein Interaction Map
Types of interactions protein (enzyme) – metabolite (ligand) metabolic pathways protein – protein cell signaling pathways, protein complexes protein – gene genetic networks
PLoS Computational Biology March 2007, Volume 3 e42 Database/URL/FTP DIP BIND MPact/MIPS STRING MINT IntAct BioGRID HPRD ProtCom 3did, Interprets Pibase, Modbase CBM ftp://ftp.ncbi.nlm.nih.gov/pub/cbmftp://ftp.ncbi.nlm.nih.gov/pub/cbm SCOPPI iPfam InterDom DIMA Prolinks Predictomehttp://predictome.bu.edu/
KEGG BioCyc Reactome GenMAPP BioCarta Pathguide – the pathway resource list Some resources
I have interactions what next? Evaluate the quality of interactions i.e. type of method used for identification….what exactly are these methods? Visualize these interactions as a network and analyze.