Framework for study
The first study, lead-authored by the CCSB's Kavitha Venkatesan, PhD, offers a framework for gauging the quality of current maps of the interactome in human cells. The maps draw on three sources of information about protein interactions: high throughput yeast two-hybrid (HT-Y2H) procedures, which use robotic equipment to screen thousands of proteins to see which bind to each other (the binding switches on a "reporter" gene that can be chemically detected); compilations of published studies on small numbers of protein interactions; and studies that predict interactions based on computational techniques. While each approach is useful, it isn't clear whether small-scale experiments provide better data than high volume screenings (as some studies have suggested), whether the interactions detected in experiments actually occur in living cells, and whether existing maps depict a small- or large-sized chunk of the entire interactome.
All experimental techniques generate some false positives -- in which interactions are "detected" that haven't really taken place -- and false negatives in which interactions that have occurred fail to be found. To weed them out, the new framework examines experimental methods from the standpoint of precision, sensitivity, and completeness. "The framework approach takes as standards interactions reported in multiple studies of high quality, and then verifies those standards against results obtained by other techniques," says Venkatesan.
Using the framework, the Dana-Farber team found that each technique captures only 20-30 percent of all the interactions within cells. That led them to determine that the human interactome contains about 130,000 interactions, a small minority of which have been mapped so far.
The second study offers researchers a tool kit for determining whether a newly discovered
|Contact: Bill Schaller|
Dana-Farber Cancer Institute