lecture24_slides

lecture24_slides - Overview of today Today: Quick review of...

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Overview of today Today: Quick review of functional analysis of clusters Introduction to protein-protein interaction networks Why are they important? How can we measure them? How are they useful? Next week: Go over Midterm #2 results More protein-protein interaction networks Quantitative analysis of networks
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How do we validate clustering results? • Biological validation (like we just saw) • Systematic comparison with established knowledge of gene function – Where can we get “established” knowledge of gene function? Answer: standardized gene function classification schemes
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Clark et al., 2005 The Gene Ont ology
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Organism-specific annotations to GO Different research groups have organized organism-specific genomic evidence (i.e. Saccharomyces Genome Database- yeast) (Borrowed liberally from the SGD website) Each gene annotation has an associated evidence code:
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Biological Process example DNA metabolism fragment
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0 5000 10000 15000 20000 December-00 December-01 December-02 December-03 December-04 December-05 December-06 December-07 December-08 Number of annotated human genes EBI GOA Biological Process annotations (non-IEA,RCA evidence codes) GO annotation progress-- human http://www.geneontology.org/GO.current.annotations.shtml
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GO annotation progress-- yeast
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Interpreting clusters from gene expression analysis “general stress response is upregulated” ? Biological interpretation Raw data
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GO enrichment analysis • Assume a cluster of n genes, chosen from N total in the genome • What is the significance of k genes overlapping with a GO term (e.g. methionine metabolism) of size M? Null hypothesis: the overlap with GO term is random, hypergeometrically distributed Solution : test the probability of observing k or more genes under the null hypothesis 1 0 1 k i n N i n M N i M value P Cluster genes GO term genes k All genes N M n
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Protein-protein interaction networks
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What else can we measure? ( adapted from Charles Mallery , http://fig.cox.miami.edu/~cmallery/150/gene/sf13x1.jpg ) Gene and protein expression Protein-protein interactions Tissue/cellular localization Genetic interactions
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What else can we measure? ( adapted from Charles Mallery , http://fig.cox.miami.edu/~cmallery/150/gene/sf13x1.jpg ) Sequence Gene and protein expression Protein-protein interactions Tissue/cellular localization Genetic interactions Samples Garber, Troyanskaya et al. Diversity of gene expression in adenocarcinoma of the lung. PNAS 2001, 98(24):13784-9. Gene expression (microarrays)
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What else can we measure? ( adapted from Charles Mallery , http://fig.cox.miami.edu/~cmallery/150/gene/sf13x1.jpg ) Sequence Gene and protein expression Protein-protein interactions Tissue/cellular localization Genetic interactions Hawoong Jeong et al. Oltvai Centrality and lethality of protein networks. Nature 411, 41-42 (2001) Protein-protein interactions Yeast PPI network:
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Hawoong Jeong et al. Oltvai Centrality and lethality of protein networks. Nature 411, 41-42 (2001) Yeast protein-protein interaction network
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Protein-protein interactions support signaling
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lecture24_slides - Overview of today Today: Quick review of...

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