TY - JOUR
T1 - Analysis of the human protein interactome and comparison with yeast, worm and fly interaction datasets
AU - Gandhi, T. K.B.
AU - Zhong, Jun
AU - Mathivanan, Suresh
AU - Karthick, L.
AU - Chandrika, K. N.
AU - Mohan, S. Sujatha
AU - Sharma, Salil
AU - Pinkert, Stefan
AU - Nagaraju, Shilpa
AU - Periaswamy, Balamurugan
AU - Mishra, Goparani
AU - Nandakumar, Kannabiran
AU - Shen, Beiyi
AU - Deshpande, Nandan
AU - Nayak, Rashmi
AU - Sarker, Malabika
AU - Boeke, Jef D.
AU - Parmigiani, Giovanni
AU - Schultz, Jörg
AU - Bader, Joel S.
AU - Pandey, Akhilesh
N1 - Funding Information:
A.P., J.D.B. and J.S.B. were supported by a grant from the National Institutes of Health (U54 RR020839). G.P. was supported by a grant from the National Science Foundation (NSF 034211), J.S.B. was supported by grants from the US National Institutes of Health (R41 GM073492 and R01 GM067761) and the Whitaker Foundation and S.P. was supported by the IZKF Würzburg project. The authors thank J. Eppig and C. Bult for providing knockout data from the Mouse Genome Database and B. Migeon, N. Katsanis and J. Mendell for helpful suggestions. The HPRD was developed with funding from the National Institutes of Health and the Institute of Bioinformatics.
PY - 2006/3
Y1 - 2006/3
N2 - 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.
AB - 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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U2 - 10.1038/ng1747
DO - 10.1038/ng1747
M3 - Article
C2 - 16501559
AN - SCOPUS:33644617753
SN - 1061-4036
VL - 38
SP - 285
EP - 293
JO - Nature Genetics
JF - Nature Genetics
IS - 3
ER -