Post-genomics: Understanding Proteomics and Protein Interaction Networks

A recent collaboration between Johns Hopkins University and the Institute of Bioinformatics in Bangalore, has produced some surprising results in protein-protein interactions. Proteins are the prime movers in the cell. Understanding how proteins interact with each other will fill in many of the gaps in our understanding of cell function--both normal and pathological.

The findings, reported in the March issue of Nature Genetics, were made using a database of more than 25,000 protein-protein interactions compiled by the Hopkins-IOB team. The result is believed to be the most detailed human "interactome" yet describing the interplay of proteins that occur in cells during health and disease.

"Genes are important because they are the blueprints for proteins, but proteins are where the action is in human life and health," says Akhilesh Pandey, M.D., Ph.D., an 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. "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," he says.

The analysis included interactions among 1,077 genes coding for proteins linked to 3,133 diseases, the researchers report. Significantly, it showed that proteins encoded by genes that are mutated in inherited disorders were likely to interact with proteins already known to cause similar disorders. In addition, the researchers disproved the long-held belief among scientists that the relative importance of a specific protein is always reflected by the number of other proteins it interacts with in the cell.

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 more than 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.

....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."

From a 2004 report in Nature, this abstract explains the goal of postgenomics:

A key aim of postgenomic biomedical research is to systematically catalogue all molecules and their interactions within a living cell. There is a clear need to understand how these molecules and the interactions between them determine the function of this enormously complex machinery, both in isolation and when surrounded by other cells. Rapid advances in network biology indicate that cellular networks are governed by universal laws and offer a new conceptual framework that could potentially revolutionize our view of biology and disease pathologies in the twenty-first century.

Here is the source for the report. Hat tip to Snowcrash at Biosingularity Blog.