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Largest study of human 'interactome' reveals a novel way

as surprising. It showed that current rapid-testing methods for identifying protein interactions are likely to miss true interactions.

Much of the Hopkins-Bangalore work was based on information compiled in the Human Protein Reference Database (HPRD), a repository of information on protein-protein interactions collected from the published literature and stored in a format suitable for rapid study and comparison with other animal cells. HPRD was developed by the IOB and the Pandey laboratory.

"Using HPRD and several other databases, we have been able to develop a gold mine of new information for researchers seeking new ways of finding candidate genes involved in genetic diseases," Pandey says. "And our demonstration that a protein's importance is not based on the number of interactions it has with other proteins is an important conceptual breakthrough. It eliminates a blind alley that could mislead researchers investigating the roles of specific proteins in the cell."

Pandey is the chief scientific advisor to the IOB and senior author of the Nature Genetics article. The team's conceptual advance was made by comparing human data with 6,014 genes in yeast and 2,284 genes in mice whose effect on survival was known, according to Pandey. "Our much larger database on genes and proteins gave us the information to set the record straight on how to measure a protein's importance," he says.

Using this kind of comprehensive comparison of information about human and other organisms allowed Pandey's group to identify 36 previously unknown protein-protein interactions, nine of which were tested in the laboratory to verify what the analysis suggested. "We proved they were valid," Pandey says. "By linking computerized sleuthing to laboratory experiments to confirm those findings, we expect to be able to eventually fill in many blanks in human protein-protein interactions."

All the analyses were primarily carried out at the IOB, a nonprofit
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Source:Johns Hopkins Medical Institutions


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