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Data visualization in the post-genomics era Carol Morita Genentech, Inc. Pre-Genomics: assembling the pieces GenBank Genome project initiated Where we are today Organism Size (bp) # genes E.coli (bacteria) 4.67 million Arabidopsis (plant) 100 million 25,000 C. elegans (worm) 97 million 19,099 Drosophila (fly) 136 million 13,061 Mouse 3 billion ~40,000 Human 3 billion ~40,000 3,237 American view of the genome Entrez Genome Browser National Center for Biotechnology Information National Institutes of Health http://www.ncbi.nlm.nih.gov:80/PMGifs/Genomes/euk_g.html European view of the genome Ensembl Genome Browser European Molecular Biology Laboratory http://www.ensembl.org/ What the genomes of model organisms tell us Maturation 10 days 9 weeks 20-25 years Genome 165 million bp 3 billion bp 3 billion bp Genes 13,600 ~40,000 ~40,000 Almost every human gene has a counterpart in the mouse and some blocks of DNA are proving impossible to tell apart Human genes mapped onto mouse chromosomes If we are so similar genetically, why are we so different? Proteomics: the real work begins Definition: Description and functional characterization of the full complement of an organism’s proteins what’s at play… – Multiple proteins can be derived from one gene – Protein interactions can be complex and are poorly understood – ‘Plasticity’ of the genome – Spatial and temporal regulation Increased diversity due to alternative splicing gene A Alternative splicing • Plays an important role in: – expanding protein diversity – generating proteins with subtle or opposing functional roles – enabling an organism to respond to environmental pressures • >35% of human genes undergo alternate splicing; probably higher Complexity due to protein interactions Death Receptor Signaling pathway DNA Microarrays Microarray chips may contain 50,000 known DNA fragments on a single slide Visualizing microarray data Source: Silicon Genetics: GeneSpring Limitations of DNA microarrays • ‘snapshots’ of the DNA activity in a cell -prefer movies! • Many important biological events cannot be detected because transcription of DNA is not involved • Protein array technology is still in its infancy The curse of dimensionality Source: Klausner, 2002 Cancer Cell1, p. 3-10