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

Area of Science:

• Systems Biology
• Metabolic Engineering
• Computational Biology

Background:

• Genome-scale metabolic models (GEMs) are crucial for biological discovery and metabolic engineering.
• Existing automated GEM reconstruction methods are often not optimized for multicellular eukaryotes, with unclear performance.
• Evaluating these tools for eukaryotic systems is essential for advancing research.

Purpose of the Study:

• To comparatively analyze seven automated reconstruction tools for generating draft GEMs in multicellular eukaryotes.
• To assess tool performance based on network properties, functional representation, and annotation quality.
• To guide researchers in selecting appropriate tools for eukaryotic GEM reconstruction.

Main Methods:

• Seven automated reconstruction tools (AuReMe, CarveMe, merlin, ModelSEED, Pathway Tools, RAVEN, Reconstructor) were applied.
• The tools were tested on three multicellular eukaryotes: Aedes aegypti, CHO cell line (Cricetulus griseus), and Ectocarpus siliculosus.
• Evaluation metrics included network size, functionality, consistency, eukaryotic features, annotation quality, and execution time.

Main Results:

• Significant differences were observed among the tools in terms of functionality and representation of eukaryotic features.
• A trade-off exists between model functionality and the accurate representation of compartmentalization and organism-specific metabolism.
• No single tool demonstrated superiority across all evaluated metrics for eukaryotic GEM reconstruction.

Conclusions:

• The performance of automated GEM reconstruction tools varies considerably for multicellular eukaryotes.
• Researchers must consider a trade-off between model comprehensiveness and the accurate depiction of eukaryotic-specific biological processes.
• This comparative analysis provides a resource for selecting the most suitable tool based on specific research objectives and organism characteristics.