Scientists at the Institute of Bioinformatics (IOB), a three-year-old a non-profit research institute, have been able to find a novel methodology to find disease targets through a large-scale analysis of interactions between proteins in human body cells, which hold promise for identifying new genes involved in genetic diseases.

The research was initiated by Dr. Akhilesh Pandey, chief scientific advisor, Institute of Bioinformatics, who is also the assistant professor at the Institute of Genetic Medicine and the departments of biological chemistry, oncology and pathology at The Johns Hopkins University School of Medicine. The findings were made using a database of more than 25,000 protein-protein interactions compiled by the Hopkins-IOB team, which is the most detailed human "interactome" describing the interplay of proteins that occur in cells during health and disease.

"Genes are important because they are the blueprints for proteins. This ability to find links between sets of proteins involved in different genetic disorders offers a novel approach for more rapidly identifying new candidate genes involved in human diseases," informed Dr Pandey.

The analysis included interactions among 1,077 genes coding for proteins linked to 3,133 diseases, the researchers report. It showed that proteins encoded by genes that are mutated in inherited disorders are likely to interact with proteins already known to cause similar disorders.

According to Pandey, the team's comparison of almost 25,000 human, 16,000 yeast, 5,500 worm, and 25,000 fly protein-protein interactions showed that among these 70,000 links, only 16 were common to all four species.

Researchers say this low level of interactome overlap among species was surprising. It showed that current rapid-testing methods for identifying protein interactions are likely to miss true interactions.

The Hopkins-IOB work was based on information compiled in the Human Protein Reference Database (HPRD), a repository of information on protein-protein interactions stored in a format suitable for rapid study and comparison with other animal cells developed by the team. Using HPRD and several other databases, the scientists had been able to develop a gold mine of new information to find candidate genes involved in genetic diseases.

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. The larger database on genes and proteins provided clues to measure a protein's importance.

The comprehensive comparison of information about human and other organisms allowed IOB to identify 36 previously unknown protein-protein interactions, nine of which were tested in the laboratory to verify the suggested analysis.

The Human Protein Reference Database was developed with funding from the National Institutes of Health and the Institute of Bioinformatics. The Institute is allowed to a share of licensing fees paid to The Johns Hopkins University by commercial entities for use of the database and the terms of these arrangements are being managed by the former in accordance with its conflict of interest policies.

The researchers are Giovanni Parmigiani, Joel Bader and Jef Boeke from Johns Hopkins and Stefan Pinkert and Joerg Schultz from the University of Wuerzburg. Scientists from IOB are TKB Gandhi, Suresh Mathivanan, Goparani Mishra, Balamurugan Periswamy, L Karthik, KN Chandrika, S Sujatha Mohan, Salil Sharma, Nandan Deshpande, Malbika Sarkar and Kannabiran Nandakumar.