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Title:
Integration of Functional Genomic Information: From Yeast to Worm Abstract:
Genomic and proteomic approaches can provide hypotheses concerning
functions for the large numbers of genes predicted from genome sequences.
However, information from these approaches should be considered with caution
due to the artificial nature of standardized high-throughput assays. Although
it is possible that biological hypotheses can be formulated by integrating
functional genomic and proteomic data from various sources, it remains
a question as to what extent the data can be correlated and how such integration
can be achieved for different organisms. We developed strategies to relate
transcriptome and interactome datasets for Saccharomyces cerevisiae and
provided global evidence that genes with similar expression profiles are
more likely to encode interacting proteins. To initiate studies on how
interactome networks relate to multicellular functions and to extend data
integration for higher organisms, we have mapped a large fraction of the
Caenorhabditis elegans interactome network. More than 4000 interactions
were identified by high-throughput yeast two-hybrid screens. Together
with already described interactions and interologs predicted in silico,
our current version of the Worm Interactome (WI5) map contains ~5500 interactions.
Using this map, we generated a neighborhood of proteins essential for
early embryogenesis. It was revealed on a global scale that physical interactors
tend to exhibit correlated loss-of-function defects during early embryogenesis.
Transcriptome and phenome information were integrated with the interactome
map. Based on topological properties of the network, predictions were
made for genes that are potentially involved in early embryogenesis and
for gene pairs of shared functions during this process. In these predictions
we recapitulated published information about early embryogenesis and provided
candidate genes or gene pairs that are of highly likely to be involved
in early embryogenesis. We propose that such integration of functional
genomic information can be applied to other biological processes and to
other organisms as well. |
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© University of Notre Dame Last Updated: Friday, November 4, 2005 |
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