Meta-Analysis of Aedes aegypti Expression Datasets: Comparing Virus Infection and Blood-Fed Transcriptomes to Identify Markers of Virus Presence

Abstract

The mosquito Aedes aegypti (L.) is vector of several arboviruses including dengue, yellow fever, chikungunya, and more recently zika. Previous transcriptomic studies have been performed to elucidate altered pathways in response to viral infection. However, the intrinsic coupling between alimentation and infection were unappreciated in these studies. Feeding is required for the initial mosquito contact with the virus and these events are highly dependent. Addressing this relationship, we reinterrogated datasets of virus-infected mosquitoes with two different diet schemes (fed and unfed mosquitoes), evaluating the metabolic cross-talk during both processes. We constructed coexpression networks with the differentially expressed genes of these comparison: virus-infected versus blood-fed mosquitoes and virus-infected versus unfed mosquitoes. Our analysis identified one module with 110 genes that correlated with infection status (representing ~0.7% of the A. aegypti genome). Furthermore, we performed a machine-learning approach and summarized the infection status using only four genes (AAEL012128, AAEL014210, AAEL002477, and AAEL005350). While three of the four genes were annotated as hypothetical proteins, AAEL012128 gene is a membrane amino acid transporter correlated with viral envelope binding. This gene alone is able to discriminate all infected samples and thus should have a key role to discriminate viral infection in the A. aegypti mosquito. Moreover, validation using external datasets found this gene as differentially expressed in four transcriptomic experiments. Therefore, these genes may serve as a proxy of viral infection in the mosquito and the others 106 identified genes provides a framework to future studies.

Aedes aegypti (Diptera: Culicidae) Immune Responses with Different Feeding Regimes Following Infection by the Entomopathogenic Fungus Metarhizium anisopliae

“…Immune activation may be a protective mechanism to combat potential invading microbes after the ingestion of a highly nutritional diet such as blood [57]. Moreover, it has been reported that pathogens present in the blood meal caused an enhanced production of immune effector molecules [55,58]. The interactions between insects and entomopathogenic fungi is complex [31,59].…”

Systems biology analysis of publicly available transcriptomic data reveals a critical link between AKR1B10 gene expression, smoking and occurrence of lung cancer

“…All The heatmap was generated in R via the heatmap.2 function from the gplots package, using the "scale = "row" switch to Z-score standardize the rows [31]. PCA was performed in order to compare and visualize the expression values of all genes to estimate the variance of the global gene expression with the function prcomp a native package in R. The decision trees were employed to validate and identify the minimal gene set that correctly classifies the smokers from nonsmokers from the 22-gene signature [32]. To estimate the decision tree models accuracy, we performed a 10-fold cross validation.…”

“…The validation set was used to test the classifier performance. The sensibility and specificity were measured from the confusion matrix and visualized in the receiver-operating characteristic curve (ROC) [32]. Accuracy was evaluated by area under the curve of ROC plot.…”

Mosquito Innate Immunity

“…Upregulation of antioxidant response proteins takes place upon the consumption of a blood meal [ 14 , 17 ]. Additionally, a blood meal elicits an immune response in the mosquito; however, it has been observed that if a blood meal is infected with a pathogen, there is an enhanced surge of immune effector molecules [ 18 , 19 , 20 , 21 , 22 , 23 ]. Specifically, there is a tissue-specific regulation of these effector molecules, as seen in mosquito genera such as Anopheles and Aedes [ 24 , 25 ].…”