Biological pathways Bing Zhang Department of Biomedical Informatics Vanderbilt University [email protected] Biological pathway A biological pathway is a series of actions among molecules in a cell that leads to a certain product or a change in a cell. Different types of biological pathways Signal transduction pathways Gene regulation pathways Metabolic pathways 2 Applied Bioinformatics, Spring 2011 Outline Pathway databases Pathway assembly and editing Pathway mapping and enrichment analysis 3 Applied Bioinformatics, Spring 2011 Selected pathway databases KEGG Kyoto Encyclopedia of Genes and Genomes http://www.genome.jp/kegg/pathway.html Reactome Ontario Institute for Cancer Research, Cold Spring Harbor Laboratory, New York University School of Medicine and The European Bioinformatics Institute http://www.reactome.org/ WikiPathways University of Maastricht and UCSF http://www.wikipathways.org/ 4 Applied Bioinformatics, Spring 2011 KEGG: data model Molecular building blocks KEGG GENES: genes and proteins generated by genome sequencing projects KEGG ORTHOLOGY: orthology (KO) groups KEGG COMPOUND: small molecules KEGG REACTIONS: biochemical reactions KEGG PATHWAY: pathway maps Created in a general way to be applicable to all organisms, in terms of the orthologs defined by KO groups Organism-specific pathways can be generated by converting KO groups to gene identifiers in a given organism 5 Applied Bioinformatics, Spring 2011 KEGG: TCA cycle 6 Applied Bioinformatics, Spring 2011 Reactome: data model Entities Nucleic acids, small molecules, proteins (with or without modifications), and macromolecular complexes Reactions Chemical transformations of classical biochemistry Transport from one compartment to another Interaction to form a complex Generalized data model allows the capture of different biological processes Human centric, can be extended to other species through orthology- based inferences 7 Applied Bioinformatics, Spring 2011 Reactome: TCA cycle 8 Applied Bioinformatics, Spring 2011 WikiPathways: open curation model Pico et al. Plos Biol 2008 9 Applied Bioinformatics, Spring 2011 WikiPathways: TCA cycle 10 Applied Bioinformatics, Spring 2011 WikiPathway: pathway editing http://wikipathways.org/index.php/Help:Tutorial 11 Applied Bioinformatics, Spring 2011 Selected pathway assembly and editing tools PathVisio Cell designer http://www.pathvisio.org/ http://www.celldesigner.org/ 12 Applied Bioinformatics, Spring 2011 Build your own pathways Viswanathan et al. PLoS Comput Biol, 2008 13 Applied Bioinformatics, Spring 2011 Pathway-based analyses 14 Applied Bioinformatics, Spring 2011 WebGestaltWebGestalt: Web-based Gene Set Analysis Toolkit 8 organisms 132 ID types http://bioinfo.vanderbilt.edu/ webgestalt 73,986 functional groups Zhang et.al. Nucleic Acids Res. 33:W741, 2005 Duncan et al. BMC Bioinformatics. 11(Suppl 4) :P10, 2010 15 CSHL Proteomics Course, 07/30/2010 WebGestalt KEGG pathway enrichment analysis 16 Applied Bioinformatics, Spring 2011 WebGestalt WikiPathways enrichment analysis 17 Applied Bioinformatics, Spring 2011 Summary Pathway databases KEGG Reactome WikiPathways Pathway assembly and editing WikiPathways/PathVisio Cell designer Pathway mapping and enrichment analysis KEGG Reactome WebGestalt Applied Bioinformatics, Spring 2011 Exercise Data set: james_west_2005_hne_6h_60vs0.txt Array platform: affy_hg_u133_plus_2 54675 probe sets Two groups (HNE0 and HNE60, three replicates in each group) Limma moderated t-test, FDR<0.01 james_west_2005_hne_6h_60vs0_limma_both.txt: 937 differentially expressed probe sets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pplied Bioinformatics, Spring 2011 .