Data visualization in the post-genomics era

Carol MoritaGenentech, Inc.

Pre-Genomics: assembling the pieces

Genome project initiated

GenBank

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

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

European view of the genome

Ensembl Genome Browser

European Molecular Biology Laboratoryhttp://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

If we are so similar genetically,why are we so different?

Human genes mapped onto mouse chromosomes

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

Source: Klausner, 2002 Cancer Cell1, p. 3-10

The curse of dimensionality