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Analysis of GO annotation at cluster level by H. Bjørn Nielsen Slides from Agnieszka S. Juncker The DNA Array Analysis Pipeline Question Experimental Design Array design Probe design Sample Preparation Hybridization Buy Chip/Array Image analysis Normalization Expression Index Calculation GO annotations Comparable Gene Expression Data Statistical Analysis Fit to Model (time series) Advanced Data Analysis Clustering Meta analysis PCA Classification Promoter Analysis Survival analysis Regulatory Network Gene Ontology Gene Ontology (GO) is a collection of controlled vocabularies describing the biology of a gene product in any organism There are 3 independent sets of vocabularies, or ontologies: • Molecular Function (MF) – e.g. ”DNA binding” and ”catalytic activity” • Cellular Component (CC) – e.g. ”organelle membrane” and ”cytoskeleton” • Biological Process (BP) – e.g. ”DNA replication” and ”response to stimulus” Gene Ontology structure GO structure, example 2 KEGG pathways • KEGG PATHWAYS: – collection of manually drawn pathway maps representing our knowledge on the molecular interaction and reaction networks, for a large selection of organisms • 1. Metabolism – Carbohydrate, Energy, Lipid, Nucleotide, Amino acid, Other amino acid, Glycan, PK/NRP, Cofactor/vitamin, Secondary metabolite, Xenobiotics • • • • • 2. Genetic Information Processing 3. Environmental Information Processing 4. Cellular Processes 5. Human Diseases 6. Drug Development KEGG pathway example 1 KEGG pathway example 2 Cluster analysis and GO Analysis example: • Partitioning clustering of genes into e.g. 10 clusters based on expression profiles • Assignment of GO terms to genes in clusters • Looking for GO terms overrepresented in clusters Hypergeometric test • The hypergeometric distribution arises from sampling from a fixed population. 20 white balls out of 100 balls 10 balls • We want to calculate the probability for drawing 7 or more white balls out of 10 balls given the distribution of balls in the urn Yeast cell cycle Sampling Time series experiment: Y Y Y Y Y Y Y Time Gene expression profiles: Gene1 Gene2 Time Exercise Find it on the course page