Abstract
Background: Malaria causes over one million deaths annually, posing an enormous health and economic burden in endemic regions. The completion of genome sequencing of the causative agents, a group of parasites in the genus Plasmodium, revealed potential drug and vaccine candidates. However, genomics-driven target discovery has been significantly hampered by our limited knowledge of the cellular networks associated with parasite development and pathogenesis. In this paper, we propose an approach based on aligning neighborhood PPI subnetworks across species to identify network components in the malaria parasite P. falciparum.Results: Instead of only relying on sequence similarities to detect functional orthologs, our approach measures the conservation between the neighborhood subnetworks in protein-protein interaction (PPI) networks in two species, P. falciparum and E. coli. 1,082 P. falciparum proteins were predicted as functional orthologs of known transcriptional regulators in the E. coli network, including general transcriptional regulators, parasite-specific transcriptional regulators in the ApiAP2 protein family, and other potential regulatory proteins. They are implicated in a variety of cellular processes involving chromatin remodeling, genome integrity, secretion, invasion, protein processing, and metabolism.Conclusions: In this proof-of-concept study, we demonstrate that a subnetwork alignment approach can reveal previously uncharacterized members of the subnetworks, which opens new opportunities to identify potential therapeutic targets and provide new insights into parasite biology, pathogenesis and virulence. This approach can be extended to other systems, especially those with poor genome annotation and a paucity of knowledge about cellular networks.
| Original language | English (US) |
|---|---|
| Article number | S5 |
| Journal | BMC Systems Biology |
| Volume | 6 |
| Issue number | SUPPL3 |
| DOIs | |
| State | Published - Dec 17 2012 |
Bibliographical note
Funding Information:We thank PlasmoDB for providing access to malaria omic data. This work is supported by NIH grants GM100806, GM081068 and AI080579 to YW. YW is also supported by NIH grant RR013646. KR and CH are supported by University of Minnesota Grant-in-Aid of Research, Artistry and Scholarship. 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 Center for Research Resources, or the National Institutes of Health. This article has been published as part of BMC Systems Biology Volume 6 Supplement 3, 2012: Proceedings of The International Conference on Intelligent Biology and Medicine (ICIBM) - Systems Biology. The full contents of the supplement are available online at http://www.biomedcentral.com/ bmcsystbiol/supplements/6/S3.
