Conca, C. | Search bioRxiv

bioRxiv2025

Selecting methods for draft GEM generation in multicellular eukaryotes: a comparative analysis

Motivated by multiple strategies that have successfully implemented genome-scale models (GEMs) into their pipeline, several approaches have been developed for automatic generation of draft GEMs. However, most of these methods are not optimized for their use for multicellular eukaryotes and their performance for this task is unclear. In this work we present a comparative analysis of seven automated reconstruction tools (AuReMe, carveMe, Merlin, modelSEED, Pathway tools, Raven and Reconstructor) applied to three multicellular eukaryotes: the mosquito Aedes aegypti, the CHO (Chinese Hamster Ovary) cell line from Cricetulus griseus and the brown algae Ectocarpus siliculosus. Evaluation of these tools was based on metrics for network size, functionality, consistency, representation of organelle-specific functions and organism-specific metabolites, annotation quality and execution time. Finding that similarity of obtained metabolic networks is highly influenced by databases in which these methods base their predictions over phylogeny. Our works aims at providing a practical resource to guide researchers in selecting methods for draft generation tailored to organism characteristics and research goals. Author summaryGenome-scale models (GEMs) represent all the potential biochemical transformations that a specific organism can carry out based on the information encoded in its genome. Although these models are a powerful tool for analyzing omics datasets and simulating the metabolic effects of genetic modifications or changing media composition, the process of manually reconstructing a genome-scale model is complex and time-consuming. Motivated by their potential applications, several tools have been developed for the automated generation of draft GEMs, however, most of them are oriented to simpler organisms such as bacteria or single-cell eukaryotes, while their relative performance for modeling multicellular eukaryotes is unclear. In this work, we compared seven tools for draft GEMs reconstruction of three organisms: for the mosquito Aedes aegypti, the brown algae Ectocarpus siliculosus and the CHO cell line from Cricetulus griseus. Our results showed that no tool systematically outperformed others, suggesting that method selection is influenced by several factors such as organism-specific data availability and their intended application.

systems biology↗

bioRxiv2023

A look into the future: Using a transcriptomic meta-analysis of Diptera-Wolbachia systems to project the sustainability of arboviral control strategies

BackgroundAn effective strategy for arboviral control consists in transfecting Aedes aegypti mosquitoes with the intracellular bacteria Wolbachia pipientis, which reduces host viral susceptibility and spreads itself into wild populations via reproductive manipulations. However, the prospect of losing the efficacy of this strategy underscores the need for deepening the mechanistic knowledge of Diptera-Wolbachia systems and identifying relevant Wolbachia effects that could decline upon adaptation of A. aegypti transfections. A systematic comparison of publicly available Diptera-Wolbachia transcriptomic datasets could yield progress in this matter. Methodology/Principal findingsWe derived differentially expressed gene (DEG) sets from previously published Diptera-Wolbachia transcriptomic datasets, subjected them to enrichment analysis of Gene Ontology terms, and intersected the results to identify patterns of host gene/function regulation by Wolbachia. A putative farnesoic acid methyl transferase (AAEL004667) and a flavin-containing monooxygenase (AAEL000834) were consistently upregulated in transfected A. aegypti and linked to cytoplasmic incompatibility and viral susceptibility, being proposed as novel targets of study. Genes implicated in viral blocking --GNBPA1, PGRPS1, DEFC, Tf1, serine-type endopeptidases and endopeptidase inhibitors-- were consistently upregulated in transfected A. aegypti but not in native infections, indicating that they could lose responsiveness to Wolbachia over time and should be considered to keep the efficacy of arboviral control. The commonality of chitinase regulation by Wolbachia was identified and proposed as an explanation for the loss of desiccation resistance in transfected A. aegyptis eggs, which is a main obstacle for the introgression of Wolbachia in mosquito populations. Conclusions/SignificanceThe present work points out relevant gene targets to consider for arboviral control sustainability and provides new hypotheses for deepening the understanding of Diptera-Wolbachia systems. Author SummaryArboviral diseases (e.g. dengue), which are mainly transmitted by the mosquito Aedes aegypti, impose a global public health crisis. An effective strategy for controlling the spread of these diseases is to artificially infect A. aegypti populations with the bacteria Wolbachia pipientis, which reduces its capacity to transmit arboviruses. However, future adaptive changes in the novel A. aegypti-Wolbachia association could diminish the efficacy of this approach. To prevent this, it is crucial to have a solid biological understanding of Wolbachia infections and predictions about specific changes that artificial infections could undergo. By analyzing publicly available biological data from Wolbachia-infected mosquitoes and flies we were able to propose new hypotheses regarding general aspects of Wolbachia infection and to identify antiviral effects of Wolbachia in A. aegypti that could decline over time, thus providing relevant information for keeping sustainability of a key arboviral control strategy.

bioinformatics↗