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Unformatted text preview: 1 1 Introduction to Gene Set Testing Peng Liu 4/17/2008 2 What we have tested for microarray data So far for the tests we have learned (2-sample t-test, moderated t-test, SAM test, etc), we are testing each individual genes to find a list (or a rank) for the differentially expressed ones. These tests are useful in detecting individual genes but has limitations. 3 Some limitations of individual testing If we have moderate changes in gene expression, we might not be able to detect any significance after controlling the multiple testing error. Sometimes, the result might be a long list of significant genes. It is difficult to interpret the results. We might have information about functional categories of genes, individual testing does not make any use of those information. 4 Gene Set Testing Alternatively, we might want to look at sets of genes and check whether a set has interesting behavior for the microarray experiment. This problem has been referred to as gene set enrichment analysis, significance analysis of functional categories or just simply testing sets of genes. 2 5 Gene Sets The gene sets are defined based on prior knowledge from biology, such as genes from known metabolic pathways or genes sharing same transcription factor binding sites. These knowledge is organized in networks of functional categories; genes are annotated to the same category by virtue of a shared biological property. 6 Databases for Annotations There are databases that provide biological annotations for known genes, such as Gene Ontology (GO) Protein Families (Pfam) Swiss-Prot Kyoto Encyclopedia of Genes and Genomes (KEGG) 7 Gene Ontology (GO) GO terms provide one example of information that is...
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- Spring '08