A Gene-Coexpression Network for Global Discovery of Conserved Genetic Modules

Joshua M. Stuart, Eran Segal, Daphne Koller, Stuart K. Kim

Science · 2003 · 2.4K citations · 25 references

TL;DR

The study aims to elucidate gene function globally by identifying coexpressed gene pairs across 3,182 microarrays from humans, flies, worms, and yeast. The authors identified these coexpressed pairs from multiple species and assembled them into a gene‑coexpression network that revealed animal‑specific components and links between newly evolved and ancient modules. The analysis uncovered 22,163 evolutionarily conserved coexpression relationships, indicating functional linkage, revealing new genes involved in core processes such as cell cycle and secretion, experimentally confirming several predictions, and identifying animal‑specific network components that connect novel and ancient modules.

Abstract

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. Manyof 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 experimentallyconfirmed the predictions implied bysome of these links and identified cell proliferation functions for several genes. By assembling these links into a gene-coexpression network, we found several components that were animal-specific as well as interrelationships between newly evolved and ancient modules.

References

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