The Human Interactome: Published, but not Complete

It has been said that the journey of a thousand miles begins with a single step. Functional genomicists took that proverbial step earlier this month when a group led by Erich Wanker, of Berlin?s Max Delbruck Center for Molecular Medicine, reported the first yeast two-hybrid-derived human interactome (or protein-protein interaction) network in the September 1 online issue of Cell.Wanker was one of three researchers working on a first draft human interactome identified by Alison McCook in our August 1 cover story. The other researchers were Marc Vidal, of the Dana-Farber Cancer Institute, Boston, and Joel Bader, of Johns Hopkins University, Baltimore. "More than 25 million protein pairs (4456 baits × 5632 preys) were examined, and 3269 interactions among 1064 baits and 1075 preys were identified," the authors write. Assessment of data quality using independent biochemical approaches like coimmunoprecipitation suggests more than 60% of the interactions are biologically real.The final network (after removing duplicate bait-prey/prey-bait pairs) contains 3186 unique interactions between 1705 proteins; 911 of those interactions are deemed high-confidence by virtue of homology with known interactions in other organisms, or by having both members share Gene Ontology annotations, for instance.I asked Akhilesh Pandey, an assistant professor at Johns Hopkins University, who directs the Human Protein Reference Database, what he thinks of the recent announcement. When Alison interviewed him for her story, he said: "The day [the human interactome] is going to be declared done by any one group, it's going to be a big story. But the next day, we won't be much better off."Pandey says he stands by this statement. ?If the message is that the interactome has been done, nothing could be further from the truth,? he says. The current study?s output represents but a fraction of all the human protein-protein interactions published in the literature and archived in HPRD and other databases, he says. (HPRD currently contains 27,330 human interactions). And it represents a drop in the ocean of all possible human protein-protein interactions, he adds: ?If there are 20,000 to 30,000 unique genes in humans, the depth we have achieved so far ? is infinitesimal.? For that matter, he notes, the worm and fly interactomes (published in late 2003 and early 2004) are also not yet finished ? a point Vidal stressed when I interviewed him for an article we published on interactome research in 2004. The real significance, Pandey concludes, is that this is the first time so many human interactions have been mapped at once. ?These are the initial larger-scale studies to look at the human interactions systematically using one method, yeast two-hybrid. It is nothing less and nothing more.?Pandey just returned from a joint Cold Spring Harbor Laboratory/Wellcome Trust Conference on Interactome Networks, the first meeting of its kind, he says. ?This is a community that is really not yet a community. So [the goal of the meeting] was to come up with ideas and bounce them around and start a concrete project? It was to develop a critical mass of people who share a common interest ? to map a human interactome.?At the meeting, he says, researchers began laying the groundwork for moving to the next phase of human interactome work. Let?s make sure to follow up on that, lest this technical tour de force remain little more than a curiosity. In the meantime, I look forward to seeing Vidal?s and Bader?s human interactome maps in the months ahead.

The Human Interactome: Published, but not Complete

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