title: Module-based subnetwork alignments reveal novel transcriptional regulators in malaria parasite Plasmodium falciparum.
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.
authors.affiliation: Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Cai
authors.forename: Changjin
authors.initials: C
authors.lastname: Hong
authors.forename: Jianying
authors.initials: J
authors.lastname: Gu
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Lilburn
authors.forename: Rui
authors.initials: R
authors.lastname: Kuang
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Wang
mesh_terms: D042002:Chromatin Assembly and Disassembly; D002874:Chromosome Mapping; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D018503:Genome, Protozoan; D023281:Genomics; D010963:Plasmodium falciparum / Q000235:genetics* / Q000378:metabolism; D060066:Protein Interaction Maps; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional; D016415:Sequence Alignment; D049490:Systems Biology
chemical_list: D015800:Protozoan Proteins