Brucellosis 2003 proceedings - PHIDIAS

Keynote Lectures
projects (localizome), etc. Such integrated maps should be valuable for a systems
biology approach to development. C. elegans is a particularly useful model organism
because of the current availability of a complete genome sequence coupled with the
fact that the major signalling pathways (i.e., Ras, Akt, Rb, p53, and DNA damage
response) are conserved in the worm. More importantly, novel interactions identified
among worm proteins can be validated through forward and reverse genetics
approaches to suggest function for novel, and in many cases, previously unknown
genes. The starting point for our work is the creation and use of the C. elegans
ORFeome, a physical collection of all expressed, protein-encoding genes cloned as
full length open reading frames (ORFs). An immediate consequence of the
ORFeome is that we are able to both verify the genome annotation and create a
resource to functionally characterize the proteome. Approximately ~12,000 ORFs
have been successfully cloned (ORFeome 1.1), of which ~4,000 correspond to genes
that have remained untouched by any cDNA or expressed sequence tag (EST).
Unexpectedly, more than 50% of predicted genes needed corrections in their intronexon
structures. Importantly, ~11,000 C. elegans proteins can now be expressed
under many conditions and characterized using various high-throughput strategies,
including large-scale interactome mapping. Coupled with other data, it appears that
at least 85% of the ~21,000 predicted C. elegans protein-encoding genes are
genuinely expressed. We suggest that similar ORFeome projects will be valuable for
other organisms. A nearly complete set of full length ORFs in multiple expression
vectors will facilitate whole-genome approaches to systems biology. Complementing
the ORFeome effort, we have recently initiated the generation of a similar resource of
all predicted promoters of C. elegans.
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Brucellosis 2003 International Research Conference