Gene Set Enrichment and Pathways Analysis

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Gene Set Enrichment and Pathways Analysis
A means to quickly understand the biological
context of one or more genes
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Applications for Pathways Analysis

• Microarray data
• e.g., GenMAPP
• One or more QTL

Chr. 1
Chr. 5
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Pathway Types

• Biochemical / Metabolic
• Signaling and Cellular Processes
• Protein Interaction
• Receptor ligand
• Phosphorylation
• Gene Regulation
• Transcription factor
• Gene Networks
• Combination of the above

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Boehringer Mannheim Wall Charts
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Boehringer Mannheim Wall Charts

• Metabolic Pathways
• Cellular and Molecular Processes

Searchable at http//www.expasy.org Click on
Roche Applied Sciences Biochemical Pathways
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Major Public Pathway Resources
Related tools DAVID GenMAPP KEGG Array

• KEGG
• The Reactome Project (CSHL/EBI)
• NetPath (HPRD)
• Protein Interaction Databases
• MIPS MMPI
• BIND
• DIP
• Others
• IntAct (EBI)
• BioCarta
• The Signaling Gateway (Nature)
• NCBIs Gene Database
• BBID-Biological Biochemical Image Database

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Kyoto Encyclopedia of Genes and Genomes (KEGG)

• Metabolism
• Carbohydrate, Energy, Lipid, Nucleotide, Amino
  acid, Other amino acid, Glycan, PK/NRP,
  Cofactor/vitamin, Secondary metabolite,
  Xenobiotics
• Genetic Information Processing
• Environmental Information Processing
• Cellular Processes
• Human Diseases
• Drug Development

http//www.genome.jp/kegg
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KEGG
Scroll down to view pathways
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KEGG
Scroll down to view disease pathways
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KEGG
Type II diabetes mellitus
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KEGG
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Coloring KEGG Pathways
STEP 1 Enter data (fold change, position)
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Coloring KEGG Pathways
STEP 2 Pick pathway
Type II diabetes
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Coloring KEGG Pathways
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The Reactome Project
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The Reactome Project
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The Reactome Project
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The Reactome Project
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NetPath (HPRD)

• Part of Human Protein Reference Database

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NetPath (HRPD)
Scroll down to get protein list
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NetPath (HRPD)
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NCBI Gene (Entrez Gene)
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DAVID Bioinformatics (NIAID)

• Functional Annotation
• Maps a gene list to
• KEGG
• Gene Ontology
• and over 40 other resources
• Enrichment analysis
• Probability that the number of genes with a
  particular annotation is significant compared to
  background
• Functional annotation clustering
• Functional Classification
• Gene ID Conversion
• Gene Name Batch Viewer

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DAVID Functional Annotation
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DAVID Functional Annotation
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DAVID Functional Annotation
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DAVID Functional Annotation
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DAVID Functional Annotation
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DAVID Functional Annotation
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DAVID Functional Annotation
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DAVID Functional Annotation

• Enrichment analysis
• For example, our input list of 300 genes has 3
  members of the p53 signaling pathway. Is that
  significant given there are 40 genes in the
  genome that are part of the pathway?
• Fishers Exact Test
• p 0.008

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DAVID Functional Annotation
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DAVID Functional Annotation
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Summary

• Pathways analysis
• Quickly understand the biological context for a
  list of genes (microarray, QTL, etc.)
• Public resources
• Growing rapidly
• Ability to paint diagrams
• DAVID Bioinformatics
• Powerful resource to map genes to many resources