MAPK Signaling Pathway AnalysisESD.342 – Spring 2006AgendaThe MAPK Signaling PathwayMAPK Pathway (Directed)Network Description and InterpretationPreliminary Model – Adjacency MatrixStatistics for MAPK Reference PathwayMAPK Reference Pathway - PajekOpen Future Directions, Project Scope1MAPK Signaling Pathway AnalysisMAPK Signaling Pathway AnalysisESD.342 ESD.342 ––Spring 2006Spring 2006March 23rd, 2006Presentation by:Gergana Bounova, Michael Hanowsky and Nandan SudarsanamFaculty: Chris Magee2Agenda• Introduction• Network Description and Interpretation• Preliminary Model and Analysis• Future Directions and Scope3The MAPK Signaling Pathway• Biological Network– Signaling pathways are used to respond to external stimuli and regulate cellular activities – MAPK’s (Mitogen Activated Protein Kinase) – Transfer information through chemical reactions. • Signaling Pathway– Data Sources: The KEGG Database– System boundaries: Inputs and Outputs– Compounds and enzymes– Activation and Inhibition4MAPK Pathway (Directed)Image removed for copyright reasons.See: http://www.genome.jp/dbget-bin/get_pathway?org_name=ko_hsa&mapno=040105Network Description and Interpretation• Nodes– Proteins and metabolites – Exist at different levels of activity• Edges– Are the paths along which information flows– Express the relationship between different proteins• Activation and Inhibition• Actions are directed6Preliminary Model – Adjacency MatrixP YXZ• The key challenge is to identify the relationships between specific nodes– All relationships are bi-directional– Nodes are de-aggregated– All relationship types are equivalentP YXZ7Statistics for MAPK Reference Pathway• Adjacency matrix – 143x143• Giant component – 126 nodes• 15 disconnected components• Stats– Network diameter: 16– Mean path length: 6.2– Deg corr: -0.338– Clust Coeff: 0.0082 (GC: 0.0094)0 1000 2000 3000020406080100histogram100102104100101degreepdf100102104100101102degreecdf0 5 10 15010203040506070histogram100101102100101102degreepdf100101102100101102103degreecdfDistributions: betweenness (top), degrees (bottom)8MAPK Reference Pathway - Pajek9Open Future Directions, Project Scope• Calculate network statistics and compare to statistic tables for other (biological) systems• Identify network structure, functional modules (motifs-recurring patterns)• Compare statistics and structural properties for pathway in different evolving species•
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