Background: According to the World Health organization, half the world's population is at risk of contracting malaria. They estimated that in 2010 there were 219 million cases of malaria, resulting in 660,000 deaths and an enormous economic burden on the countries where malaria is endemic. The adoption of various high-throughput genomics-based techniques by malaria researchers has meant that new avenues to the study of this disease are being explored and new targets for controlling the disease are being developed. Here, we apply a novel neighborhood subnetwork alignment approach to identify the interacting elements that help regulate the cell cycle of the malaria parasite Plasmodium falciparum.Results: Our novel subnetwork alignment approach was used to compare networks in Escherichia coli and P. falciparum. Some 574 P. falciparum proteins were revealed as functional orthologs of known cell cycle proteins in E. coli. Over one third of these predicted functional orthologs were annotated as "conserved Plasmodium proteins" or "putative uncharacterized proteins" of unknown function. The predicted functionalities included cyclins, kinases, surface antigens, transcriptional regulators and various functions related to DNA replication, repair and cell division.Conclusions: The results of our analysis demonstrate the power of our subnetwork alignment approach to assign functionality to previously unannotated proteins. Here, the focus was on proteins involved in cell cycle regulation. These proteins are involved in the control of diverse aspects of the parasite lifecycle and of important aspects of pathogenesis.
Bibliographical noteFunding Information:
We thank PlasmoDB for providing access to malaria omic data. This work is supported by NIH grants GM100806, GM081068 and AI080579 to YW. KR and CH are supported by University of Minnesota Grant-in-Aid of Research, Artistry and Scholarship. We thank the Computational Biology Initiative at UTSA for providing computational support. This work received computational support from Computational System Biology Core, funded by the National Institute on Minority Health and Health Disparities (G12MD007591) from the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute on Minority Health and Health Disparities, or the National Institutes of Health.