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Published Online August 21, 2003
Science DOI: 10.1126/science.1087447

Research Articles

Submitted on May 30, 2003
Accepted on August 13, 2003

A Gene Coexpression Network for Global Discovery of Conserved Genetic Modules

Joshua M. Stuart 1, Eran Segal 2, Daphne Koller 2*, Stuart K. Kim 3*

1 Stanford Medical Informatics, 251 Campus Drive, MSOB X-215, Stanford, CA 94305-5329, USA.
2 Computer Science Department, Gates Building 1A, Stanford University, Stanford, CA 94305-9010, USA.
3 Departments of Developmental Biology and Genetics, Stanford University School of Medicine, Stanford, CA 94305-5329, USA.

* To whom correspondence should be addressed. E-mail: koller{at}cs.stanford.edu, kim{at}cmgm.stanford.edu.

To elucidate gene function on a global scale, we identified pairs of genes that are coexpressed over 3182 DNA microarrays from humans, flies, worms, and yeast. We found 22,163 such coexpression relationships, each of which has been conserved across evolution. This conservation implies that the coexpression of these gene pairs confers a selective advantage and therefore that these genes are functionally related. Many of these relationships provide strong evidence for the involvement of new genes in core biological functions such as the cell cycle, secretion, and protein expression. We experimentally confirmed the predictions implied by some of these links and identified cell proliferation functions for several genes. We assembled these links into a gene coexpression network consisting of 12 large components, and found several that were animal-specific as well as interrelationships between newly evolved and ancient modules.


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