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

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 approximately 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.