Comparative Interactomics

By creating maps of the body's complex molecular inter­actions, Trey Ideker is providing new ways to find drugs.

By Jon Cohen

This article is the first in a series of 10 stories we're running over two weeks, covering today's most significant (and just plain cool) emerging technologies. It's part of our annual "10 Emerging Technologies" report, which appears in the March/April print issue of Technology Review.

Biomedical research these days seems to be all about the "omes": genomes, proteomes, metabolomes. Beyond all these lies the mother of all omes -- or maybe just the ome du jour: the interactome. Every cell hosts a vast array of interactions among genes, RNA, metabolites, and proteins. The impossibly complex map of all these interactions is, in the language of systems biology, the interactome.

Trey Ideker, a molecular biotechnologist by way of electrical engineering, has recently begun comparing what he calls the "circuitry" of the interactomes of different species. "It's really an incremental step in terms of the concepts, but it's a major leap forward in that we can gather and analyze completely new types of information to characterize biological systems," says Ideker, who runs the Laboratory for Integrative Network Biology at the University of California, San Diego. "I think it's going to be cool to map out the circuitry of all these cells."

Beyond the cool factor, Ideker and other leaders in the nascent field of interactomics hope that their work may help uncover new drugs, improve existing drugs by providing a better understanding of how they work, and even lead to computerized models of toxicity that could replace studies now conducted on animals. "Disease and drugs are about pathways," Ideker says.

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Ideker made a big splash in the field in 2001 while still a graduate student with Leroy Hood at the Institute for Systems Biology in Seattle. In a paper for Science, Ideker, Hood, and coworkers described in startling detail how yeast cells use sugar. They presented a wiring-like diagram illustrating everything from the suite of genes involved, to the protein-protein interactions, to how perturbing the system altered different biochemical pathways. "His contribution was really special," says geneticist Marc Vidal of the Dana-Farber Cancer Institute in Boston, who introduced the concept that interactomes can be conserved between species. "He came up with one of the first good visualization tools."

Last November, Ideker's team turned heads by reporting in Nature that it had aggregated in one database all the available protein-protein interactomes of yeast, the fruit fly, the nematode worm, and the malaria-causing parasite Plasmodium falciparum. Though there's nothing particularly novel about comparing proteins across species, Ideker's lab is one of the few that has begun hunting for similarities and differences between the protein-protein interactions of widely different creatures. It turns out that the interactomes of yeast, fly, and worm include interactions called protein complexes that have some similarities between them. This conservation across species indicates that the interactions may serve some vital purpose. But Plasmodium, oddly, shares no protein complexes with worm or fly and only three with yeast. "For a while, we struggled to figure out what was going wrong with our analysis," says Ideker. After rechecking their data, Ideker and his team concluded that Plasmodium probably just had a somewhat different interactome.