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

Abstract

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.