A38B489Ad01 - Systems Biology 1 Academic year 2009 - 2010...

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Unformatted text preview: Systems Biology 1 Academic year 2009 - 2010 Systems Biology Systems Biology Phenome Phenome profiling profiling Phenome Phenome profiling profiling From microorganisms to human diseases From microorganisms to human diseases Prof. Dr. Pierre Hilson Prof. Dr. Pierre Hilson VIB Department of Plant Systems Biology VIB Department of Plant Systems Biology University of Ghent University of Ghent Academic year 2009 Academic year 2009-2010 2010 Outline- Phenome- Yeast functional genome profiling- Systematic genetic interaction mapping- Integration of phenome profiles with other data types data types- Building cancer gene/protein networks- Defining the “diseasome” Systems Biology 2 Academic year 2009 - 2010 Genome-wide phenotypic analysis ¤ Classical genetic screens ¤ Classical genetic screens – Saturated mutagenesis to isolate all the genes that, when mutated, exhibit a specific phenotype exhibit a specific phenotype – Drawback is that positional cloning or identification of a mutation is often slow and laborious often slow and laborious ¤ Reverse genetic screens – systematic approaches to identify functions for predicted genes • Insertion-based screens – Examples from yeast (transposon or recombination cassette, lof or gof) • RNA interference (RNAi) – Example from worm, fly, human and Arabidopsis Outline- Phenome- Yeast functional genome profiling- Systematic genetic interaction mapping- Integration of phenome profiles with other data types data types- Building cancer gene/protein networks- Defining the “diseasome” Systems Biology 3 Academic year 2009 - 2010 Functional profiling of the yeast genome Giaever et al (2002) Nature 418: 387 ¤ Collection of gene-deletion strains ¤ Collection of gene deletion strains ¤ Each deletion marked with a specific “molecular bar code” ¤ Quantitative assessment of fitness contribution by hybridization to high-density oligonucleotide arrays hybridization to high density oligonucleotide arrays ¤ Analysis of six well-studied conditions: – high salt, sorbitol, galactose, pH 8, minimal medium and treatment with the antifungal compound nystatin ¤ Comparison to transcription profiling experiments The gene-deletion collection ¤ Advantages Complete loss of function ( not always good! – Complete loss of function (… not always good!) – Mutated gene identified beforehand – Saturation assured (… yet, depends of the quality of the genome annotation) ¤ Construction – 5,916 gene deleted (96.5% of attempted) • 18.5% essential in glucose rich medium Giaever et al (2002) Nature 418: 387 Systems Biology 4 Academic year 2009 - 2010 Experimental design ¤ P l l l t h i i t i i l l d l ti t i ¤ Parallel growth in a mix containing all gene-deletion strains ¤ PCR amplification of molecular bar code tags from genomic DNA, with biotin-labeled primers ¤ H b idi ti t l t li l tid t ¤ Hybridization to complementary oligonucleotide arrays to quantify in a single assay the representation of each individual strain...
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This note was uploaded on 05/30/2010 for the course WE CMBIBI0200 taught by Professor Pierrehilson during the Spring '10 term at Ghent University.

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A38B489Ad01 - Systems Biology 1 Academic year 2009 - 2010...

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