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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Applied Bioinformatics, Spring 2011