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Data visualization in the post-genomics era
Carol MoritaGenentech, Inc.
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Pre-Genomics: assembling the pieces
Genome project initiated
GenBank
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Where we are today
Organism Size (bp) # genes
E.coli (bacteria) 4.67 million 3,237
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
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American view of the genome
Entrez Genome Browser
National Center for Biotechnology InformationNational Institutes of Health
http://www.ncbi.nlm.nih.gov:80/PMGifs/Genomes/euk_g.html
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European view of the genome
Ensembl Genome Browser
European Molecular Biology Laboratoryhttp://www.ensembl.org/
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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
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If we are so similar genetically,why are we so different?
Human genes mapped onto mouse chromosomes
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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
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Increased diversity due to alternative splicing
gene A
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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
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Complexity due to protein interactions
Death Receptor Signaling pathway
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DNA Microarrays
Microarray chips may contain 50,000
known DNA fragments on a single slide
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Visualizing microarray data
Source: Silicon Genetics: GeneSpring
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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
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Source: Klausner, 2002 Cancer Cell1, p. 3-10
The curse of dimensionality