Key gene modules and hub genes associated with pyrethroid and organophosphate resistance in Anopheles mosquitoes: a systems biology approach.

Publisher: BioMed Central Country of Publication: England NLM ID: 100965258 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2164 (Electronic) Linking ISSN: 14712164 NLM ISO Abbreviation: BMC Genomics Subsets: MEDLINE

Original Publication: London : BioMed Central, [2000-

Anopheles*/genetics ; Anopheles*/drug effects ; Insecticide Resistance*/genetics ; Pyrethrins*/pharmacology ; Systems Biology*; Animals ; Insecticides/pharmacology ; Gene Regulatory Networks ; Organophosphates/pharmacology ; Mosquito Vectors/genetics ; Mosquito Vectors/drug effects ; Kenya ; Gene Expression Profiling

Indoor residual spraying (IRS) and insecticide-treated nets (ITNs) are the main methods used to control mosquito populations for malaria prevention. The efficacy of these strategies is threatened by the spread of insecticide resistance (IR), limiting the success of malaria control. Studies of the genetic evolution leading to insecticide resistance could enable the identification of molecular markers that can be used for IR surveillance and an improved understanding of the molecular mechanisms associated with IR. This study used a weighted gene co-expression network analysis (WGCNA) algorithm, a systems biology approach, to identify genes with similar co-expression patterns (modules) and hub genes that are potential molecular markers for insecticide resistance surveillance in Kenya and Benin. A total of 20 and 26 gene co-expression modules were identified via average linkage hierarchical clustering from Anopheles arabiensis and An. gambiae, respectively, and hub genes (highly connected genes) were identified within each module. Three specific genes stood out: serine protease, E3 ubiquitin-protein ligase, and cuticular proteins, which were top hub genes in both species and could serve as potential markers and targets for monitoring IR in these malaria vectors. In addition to the identified markers, we explored molecular mechanisms using enrichment maps that revealed a complex process involving multiple steps, from odorant binding and neuronal signaling to cellular responses, immune modulation, cellular metabolism, and gene regulation. Incorporation of these dynamics into the development of new insecticides and the tracking of insecticide resistance could improve the sustainable and cost-effective deployment of interventions.
(© 2024. The Author(s).)

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Keywords: Anopheles arabiensis; Anopheles gambiae; Hub genes; Insecticide resistance; Molecular markers

0 (Pyrethrins)
0 (Insecticides)
0 (Organophosphates)

Date Created: 20240703 Date Completed: 20240703 Latest Revision: 20240706

20240706

PMC11223346

10.1186/s12864-024-10572-z

38961324