Disease specific modules and hub genes for intervention strategies: A co-expression network based approach for Plasmodium falciparum clinical isolates

•A Plasmodium falciparum weighted gene co-expression network was created.•A total of 12 severe disease specific modules were identified.•Many important biological pathways were identified.•Some of the hub genes identified encoded hypothetical proteins.•The hub genes may serve as candidates for inter...

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Published in:Infection, genetics and evolution genetics and evolution, 2015-10, Vol.35, p.96-108
Main Authors: Subudhi, Amit Kumar, Boopathi, Pon Arunachalam, Pandey, Isha, Kaur, Ramandeep, Middha, Sheetal, Acharya, Jyoti, Kochar, Sanjay K., Kochar, Dhanpat K., Das, Ashis
Format: Article
Language:English
Subjects:
Complicated malaria
Computational Biology - methods
Gene Expression
Gene Expression Profiling
Gene Expression Regulation
Gene Regulatory Networks
Humans
Malaria, Falciparum - complications
Malaria, Falciparum - parasitology
Oligonucleotide Array Sequence Analysis
Plasmodium falciparum
Plasmodium falciparum - genetics
Plasmodium falciparum - isolation & purification
Protozoan Proteins - genetics
Weighted gene co-expression network
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Summary:•A Plasmodium falciparum weighted gene co-expression network was created.•A total of 12 severe disease specific modules were identified.•Many important biological pathways were identified.•Some of the hub genes identified encoded hypothetical proteins.•The hub genes may serve as candidates for intervention strategies. Systems biology approaches that are based on gene expression and bioinformatics analysis have been successful in predicting the functions of many genes in Plasmodium falciparum, a protozoan parasite responsible for most of the deaths due to malaria. However, approaches that can provide information about the biological processes that are active in this parasite in vivo during complicated malaria conditions have been scarcely deployed. Here we report the analysis of a weighted gene co-expression based network for P. falciparum, from non-cerebral clinical complications. Gene expression profiles of 20 P. falciparum clinical isolates were utilized to construct the same. A total of 20 highly interacting modules were identified post network creation. In 12 of these modules, at least 10% of the member genes, were found to be differentially regulated in parasites from patient isolates showing complications, when compared with those from patients with uncomplicated disease. Enrichment analysis helped identify biological processes like oxidation–reduction, electron transport chain, protein synthesis, ubiquitin dependent catabolic processes, RNA binding and purine nucleotide metabolic processes as associated with these modules. Additionally, for each module, highly connected hub genes were identified. Detailed functional analysis of many of these, which have known annotated functions underline their importance in parasite development and survival. This suggests, that other hub genes with unknown functions may also be playing crucial roles in parasite biology, and, are potential candidates for intervention strategies.
ISSN:1567-1348
1567-7257
DOI:10.1016/j.meegid.2015.08.007