title: Inference of the oxidative stress network in Anopheles stephensi upon Plasmodium infection.
abstract: Ookinete invasion of Anopheles midgut is a critical step for malaria transmission; the parasite numbers drop drastically and practically reach a minimum during the parasite's whole life cycle. At this stage, the parasite as well as the vector undergoes immense oxidative stress. Thereafter, the vector undergoes oxidative stress at different time points as the parasite invades its tissues during the parasite development. The present study was undertaken to reconstruct the network of differentially expressed genes involved in oxidative stress in Anopheles stephensi during Plasmodium development and maturation in the midgut. Using high throughput next generation sequencing methods, we generated the transcriptome of the An. stephensi midgut during Plasmodium vinckei petteri oocyst invasion of the midgut epithelium. Further, we utilized large datasets available on public domain on Anopheles during Plasmodium ookinete invasion and Drosophila datasets and arrived upon clusters of genes that may play a role in oxidative stress. Finally, we used support vector machines for the functional prediction of the un-annotated genes of An. stephensi. Integrating the results from all the different data analyses, we identified a total of 516 genes that were involved in oxidative stress in An. stephensi during Plasmodium development. The significantly regulated genes were further extracted from this gene cluster and used to infer an oxidative stress network of An. stephensi. Using system biology approaches, we have been able to ascertain the role of several putative genes in An. stephensi with respect to oxidative stress. Further experimental validations of these genes are underway.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors.forename: Jatin
authors.initials: J
authors.lastname: Shrinet
authors.affiliation: Bioinformatics Laboratory, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Umesh Kumar
authors.initials: UK
authors.lastname: Nandal
authors.affiliation: National Institute of Malaria Research, New Delhi, India.
authors.forename: Tridibes
authors.initials: T
authors.lastname: Adak
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors.forename: Raj K
authors.initials: RK
authors.lastname: Bhatnagar
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors.forename: Sujatha
authors.initials: S
authors.lastname: Sunil
mesh_terms: D000818:Animals; D000852:Anopheles / Q000235:genetics / Q000378:metabolism* / Q000469:parasitology; D004843:Epistasis, Genetic; D005260:Female; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000469:parasitology; D053263:Gene Regulatory Networks; D017344:Genes, Insect; D006790:Host-Parasite Interactions; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D007303:Insect Vectors / Q000235:genetics / Q000378:metabolism* / Q000469:parasitology; D053858:Metabolic Networks and Pathways; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010961:Plasmodium / Q000502:physiology*; D059467:Transcriptome
chemical_list: D019476:Insect Proteins