Analysis of the human protein interactome and comparison with yeast, worm and fly interaction datasets

• Published in: Nature genetics Vol. 38; no. 3; pp. 285 - 293
• Main Authors: Pandey, Akhilesh, Gandhi, T K B, Zhong, Jun, Mathivanan, Suresh, Karthick, L, Chandrika, K N, Mohan, S Sujatha, Sharma, Salil, Pinkert, Stefan, Nagaraju, Shilpa, Periaswamy, Balamurugan, Mishra, Goparani, Nandakumar, Kannabiran, Shen, Beiyi, Deshpande, Nandan, Nayak, Rashmi, Sarker, Malabika, Boeke, Jef D, Parmigiani, Giovanni, Schultz, Jörg, Bader, Joel S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01-03-2006
• Subjects: Animals; Biological and medical sciences; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans Proteins - genetics; Comparative analysis; Diagnosis; Diptera; Drosophila melanogaster; Drosophila Proteins - genetics; Evolution, Molecular; Fundamental and applied biological sciences. Psychology; Genetic aspects; Genetic disorders; Genetics of eukaryotes. Biological and molecular evolution; Humans; Insects; Physiological aspects; Protein-protein interactions; Proteins; Proteome - genetics; Proteomics; Risk factors; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins - genetics; Worms; Yeast; Yeasts; United States; Human; Caenorhabditis elegans; Yeast; Analysis; Helmintha; Nemathelminthia; Invertebrata; Nematoda; Protein
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng1747

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.