Nature Genetics 38, 285 - 293 (2006)
Published online: 24 February 2006; | doi:10.1038/ng1747
Analysis of the human protein interactome and comparison with yeast, worm and fly interaction datasetsT K B Gandhi1, Jun Zhong2, Suresh Mathivanan1, L Karthick1, K N Chandrika1, S Sujatha Mohan1, Salil Sharma1, 2, Stefan Pinkert3, Shilpa Nagaraju1, Balamurugan Periaswamy1, Goparani Mishra1, Kannabiran Nandakumar1, Beiyi Shen2, Nandan Deshpande1, Rashmi Nayak1, Malabika Sarker1, Jef D Boeke5, 6, Giovanni Parmigiani4, Jörg Schultz3, Joel S Bader5, 7
& Akhilesh Pandey2, 41
Institute of Bioinformatics, International Technology Park, Bangalore 560 066, India. 2
McKusick-Nathans Institute of Genetic Medicine and the Departments of Biological Chemistry and Pathology, Johns Hopkins University, Baltimore, Maryland 21205, USA. 3
Department of Bioinformatics, Biozentrum, University Würzburg, Am Hubland, 97074 Würzburg, Germany. 4
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland 21205, USA. 5
The High Throughput Biology Center, Johns Hopkins University, Baltimore, Maryland 21205, USA. 6
Department of Molecular Biology and Genetics, Johns Hopkins University, Baltimore, Maryland 21205, USA. 7
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Correspondence should be addressed to Akhilesh Pandey pandey@jhmi.edu We present the first analysis of the human proteome with regard to interactions between proteins. We also compare the human interactome with the available interaction datasets from yeast (Saccharomyces cerevisiae), worm (Caenorhabditis elegans) and fly (Drosophila melanogaster). Of >70,000 binary interactions, only 42 were common to human, worm and fly, and only 16 were common to all four datasets. An additional 36 interactions were common to fly and worm but were not observed in humans, although a coimmunoprecipitation assay showed that 9 of the interactions do occur in humans. A re-examination of the connectivity of essential genes in yeast and humans indicated that the available data do not support the presumption that the number of interaction partners can accurately predict whether a gene is essential. Finally, we found that proteins encoded by genes mutated in inherited genetic disorders are likely to interact with proteins known to cause similar disorders, suggesting the existence of disease subnetworks. The human interaction map constructed from our analysis should facilitate an integrative systems biology approach to elucidating the cellular networks that contribute to health and disease states.
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