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GCB/CIS 535 Microarray Topics John Tobias November 15 th, 2004
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Overview Similarity / Clustering Applications Gene List Annotation Statistical Significance of Over Representation Public Data Formats and Databases
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Overview Similarity / Clustering Applications Gene List Annotation Statistical Significance of Over Representation Public Data Formats and Databases
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Sample Clustering Quality Control Class Discovery
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Similarity to Pattern of Interest Can use real or hypothetical gene Rank all other genes by similarity
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Hierarchical Clustering Group by expression No clear number of clusters Can define clusters by “pruning tree”
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Binning by Expression K-means Clustering Self Organizing Maps QT Clustering
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Binning By Expression K-means and SOM Groups genes into pre-determined number of clusters K-means Self Organizing Map
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Comparing Clusters Another Look Hierarchical tree trimmed to 6 clusters K-means 6 clusters Coincidence between two methods
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Binning By Expression QT Clustering Control quality and minimum size of clusters Genes may remain unclustered
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Overview Similarity / Clustering Applications Gene List Annotation Statistical Significance of Over Representation Public Data Formats and Databases
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The Gene Ontology (GO) http://www.geneontology.org/ Network of defined biological terms Three main branches Biological Process Molecular Function Cellular Component
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Gene List Annotation Pathways Functional Groups Affymetrix GeneSpring DAVID GoMiner GenMapp http://apps1.niaid.nih.gov/david/
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Identifiers to Knowledge
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Ingenuity Pathway Analysis http://www.ingenuity.co m Curated Interaction and Pathway Database Mine literature as it relates to gene list Associate function with both gene lists and interaction networks
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Overview Similarity / Clustering Applications Gene List Annotation Statistical Significance of Over Representation Public Data Formats and Databases
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Gene List Overlap with Pathways GeneSpring EASE S+ArrayAnalyzer
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Over Representation Genes on array - pathway X or O - overall 50/50 Does a gene list over represent one of the pathways? Fisher Exact Test
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EASE Expression Analysis Systematic Explorer http://david.niaid.nih. gov/david Statistical analysis of category over- representation Many choices of category lists available
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EASE Output
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Overview Similarity / Clustering Applications Gene List Annotation Statistical Significance of Over Representation Public Data Formats and Databases
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MGED Microarray Gene Expression Data (MGED) Society Organization devoted to facilitation of sharing microarray data CBIL group at UPenn key contributors Focus on standards for microarray data annotation and exchange Creation of software and databases
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MIAME Minimum Information About a Microarray Experiment required to interpret and verify the results Required by many journals Explicit guidelines for: Sample description Experimental design Array technology Protocols Analytical methods
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Public Microarray Databases ArrayExpress (EBI) http://www.ebi.ac.uk/arrayexpress/ GEO (NCBI) http://www.ncbi.nlm.nih.gov/geo/ CIBEX (NIG) http://cibex.nig.ac.jp/
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Contact Information Penn Bioinformatics Core - 13th Floor Blockley Hall John Tobias - 1314 - jtobias@pcbi.upenn.edu Reserve Computers http://core.pcbi.upenn.edu/
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