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Malaria caused by Plasmodium vivax can lead to severe morbidity and death. In addition, resistance has been reported to existing drugs in treating this malaria. Therefore, the identification of new human proteins associated with malaria is urgently needed for the development of additional drugs. In this study, we established an analysis framework to predict human- P. vivax protein associations using network topological profiles from a heterogeneous network structure of human and P. vivax, machine-learning techniques and statistical analysis. Novel associations were predicted and ranked to determine the importance of human proteins associated with malaria. With the best-ranking score, 411 human proteins were identified as promising proteins. Their regulations and functions were statistically analyzed, which led to the identification of proteins involved in the regulation of membrane and vesicle formation, and proteasome complexes as potential targets for the treatment of P. vivax malaria. In conclusion, by integrating related data, our analysis was efficient in identifying potential targets providing an insight into human-parasite protein associations. Furthermore, generalizing this model could allow researchers to gain further insights into other diseases and enhance the field of biomedical science. [ABSTRACT FROM AUTHOR]

The associations between proteins and diseases are crucial information for investigating pathological mechanisms. However, the number of known and reliable protein-disease associations is quite small. In this study, an analysis framework to infer associations between proteins and diseases was developed based on a large data set of a human protein-protein interaction network integrating an effective network search, namely, the reverse k-nearest neighbor (RkNN) search. The RkNN search was used to identify an impact of a protein on other proteins. Then, associations between proteins and diseases were inferred statistically. The method using the RkNN search yielded a much higher precision than a random selection, standard nearest neighbor search, or when applying the method to a random protein-protein interaction network. All protein-disease pair candidates were verified by a literature search. Supporting evidence for 596 pairs was identified. In addition, cluster analysis of these candidates revealed 10 promising groups of diseases to be further investigated experimentally. This method can be used to identify novel associations to better understand complex relationships between proteins and diseases. [ABSTRACT FROM AUTHOR]