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

http://www.geneontology.org/

GO Enrichment Analysis DAVID: http://david.abcc.ncifcrf.gov/ GOStat: http://gostat.wehi.edu.au/ EasyGO: http://bioinformatics.cau.edu.cn/easygo/ AmiGO

http://amigo.geneontology.org/cgi-bin/amigo/term_enrichment (does not use IEA)

Onto-Express & OE2GO http://vortex.cs.wayne.edu/projects.htm

GOEAST http://omicslab.genetics.ac.cn/GOEAST http://www.geneontology.org/GO.tools.shtml 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 BiologyModels 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/FTPDIP http://dip.doe-mbi.ucla.eduBIND http://bind.ca MPact/MIPS http://mips.gsf.de/services/ppi STRING http://string.embl.deMINT http://mint.bio.uniroma2.it/mintIntAct http://www.ebi.ac.uk/intactBioGRID http://www.thebiogrid.orgHPRD http://www.hprd.orgProtCom http://www.ces.clemson.edu/compbio/ProtCom3did, Interprets http://gatealoy.pcb.ub.es/3did/Pibase, Modbase http://alto.compbio.ucsf.edu/pibaseCBM ftp://ftp.ncbi.nlm.nih.gov/pub/cbmSCOPPI http://www.scoppi.org/iPfam http://www.sanger.ac.uk/Software/Pfam/iPfamInterDom http://interdom.lit.org.sgDIMA http://mips.gsf.de/genre/proj/dima/index.htmlProlinks http://prolinks.doe-mbi.ucla.edu/cgibin/functionator/pronav/Predictome http://predictome.bu.edu/

KEGG http://www.genome.jp/kegg/pathway.html/BioCyc http://www.biocyc.org/Reactome http://www.reactome.org/GenMAPP http://www.genmapp.org/BioCarta http://www.biocarta.com/

Pathguide – the pathway resource list http://www.pathguide.org/

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.