Navigation Links
Largest study of human 'interactome' reveals a novel way

Discoveries made during the first large-scale analysis of interactions between proteins in our cells hold promise for identifying new genes involved in genetic diseases, according to researchers at Johns Hopkins and the Institute of Bioinformatics (IOB) in Bangalore.

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 w 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 research institute founded by Pandey in May 2002. The Human Protein Reference Database was developed with funding from the National Institutes of Health and the Institute of Bioinformatics. Pandey serves as chief scientific advisor to the Institute of Bioinformatics. He is entitled to a share of licensing fees paid to The Johns Hopkins University by commercial entities for use of the database. The terms of these arrangements are being managed by The Johns Hopkins University in accordance with its conflict of interest policies.


Source:Johns Hopkins Medical Institutions

Related biology news :

1. Largest computational biology simulation mimics life’s most essential nanomachine
2. Largest genomic search finds genes that may contribute to autism
3. Bioartificial kidney under study at MCG
4. W.M. Keck Foundation funds study of friendly microbes
5. Yellowstone microbes fueled by hydrogen, according to U. of Colorado study
6. Genome-wide mouse study yields link to human leukemia
7. Clam embryo study shows pollutant mixture adversely affects nerve cell development
8. New imaging method gives early indication if brain cancer therapy is effective, U-M study shows
9. Same mutation aided evolution in many fish species, Stanford study finds
10. Sequencing of marine bacterium will help study of cell communication
11. Genetically modified rice in China benefits farmers health, study finds
Post Your Comments:

(Date:10/29/2015)... Oct. 29, 2015  Connected health pioneer, Joseph ... explosion of technology-enabled health and wellness, and the business ... The Internet of Healthy Things . ... smartphones even existed, Dr. Kvedar, vice president, Connected Health, ... care delivery, moving care from the hospital or doctor,s ...
(Date:10/27/2015)... Munich, Germany , ... (ASGM) automatically maps data from mobile eye tracking videos ... so that they can be quantitatively analyzed with SMI,s ... Germany , October 28-29, 2015. SMI,s Automated Semantic ... eye tracking videos created with SMI,s Eye Tracking ...
(Date:10/26/2015)... Oct. 26, 2015  Delta ID Inc., a company ... mobile and PC devices, announced its ActiveIRIS® technology powers ... NX F-02H launched by NTT DOCOMO, INC in ... the second smartphone to include iris recognition technology, after ... NX F-04G in May 2015, world,s first smartphone to ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... ANGELES and HOLLISTON, Mass. ... Technology, Inc. (Nasdaq: HART ), a biotechnology company ... that CEO Jim McGorry will present at ... December 1, 2015 at 2:30 p.m. PT. The presentation ... below) for 30 days. Management will also be available ...
(Date:11/25/2015)... , Nov. 25, 2015 /PRNewswire/ - Aeterna Zentaris ... that its business and prospects remain fundamentally strong ... Zoptrex™ (zoptarelin doxorubicin) recently received DSMB recommendation to ... completion following review of the final interim efficacy ... 2 Primary Endpoint in men with heavily pretreated ...
(Date:11/25/2015)... 25, 2015 Orexigen® Therapeutics, Inc. (Nasdaq: ... a fireside chat discussion at the Piper Jaffray 27th ... . The discussion is scheduled for Wednesday, December 2, ... .  A replay will be available for 14 days ... , Julie NormartVP, Corporate Communications and Business Development , ...
(Date:11/25/2015)... CA (PRWEB) , ... November 25, 2015 , ... ... genomics company uBiome, were featured on AngelList early in their initial angel funding ... an AngelList syndicate for individuals looking to make early stage investments in the ...
Breaking Biology Technology: