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Nucleic Acids Research Advance Access published online on May 25, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm254
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© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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CytoSVM: an advanced server for identification of cytokine-receptor interactions

Jin-Rui Xu1, Jing-Xian Zhang1, Bu-Cong Han1, Liang Liang1 and Zhi-Liang Ji1,2,*

1Key Laboratory for Cell Biology & Tumor Cell Engineering, the Ministry of Education of China, School of Life Sciences and 2The Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen 361005, FuJian Province, P R China

*To whom correspondence should be addressed. Tel: 86-0592-2182897; Fax: 86-0592-2181015; Email: appo{at}bioinf.xmu.edu.cn; zhiliang.ji{at}gmail.com;

Received January 23, 2007. Revised March 24, 2007. Accepted April 8, 2007.

The interactions between cytokines and their complementary receptors are the gateways to properly understand a large variety of cytokine-specific cellular activities such as immunological responses and cell differentiation. To discover novel cytokine-receptor interactions, an advanced support vector machines (SVMs) model, CytoSVM, was constructed in this study. This model was iteratively trained using 449 mammal (except rat) cytokine-receptor interactions and about 1 million virtually generated positive and negative vectors in an enriched way. Final independent evaluation by rat's data received sensitivity of 97.4%, specificity of 99.2% and the Matthews correlation coefficient (MCC) of 0.89. This performance is better than normal SVM-based models. Upon this well-optimized model, a web-based server was created to accept primary protein sequence and present its probabilities to interact with one or several cytokines. Moreover, this model was applied to identify putative cytokine-receptor pairs in the whole genomes of human and mouse. Excluding currently known cytokine-receptor interactions, total 1609 novel cytokine-receptor pairs were discovered from human genome with probability ~80% after further transmembrane analysis. These cover 220 novel receptors (excluding their isoforms) for 126 human cytokines. The screening results have been deposited in a database. Both the server and the database can be freely accessed at http://bioinf.xmu.edu.cn/software/cytosvm/cytosvm.php.

The authors wish it to be known that, in their opinion, the second and third authors contributed equally to this work.


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