On the reconstruction of the Mus musculus genome-scale metabolic network model

Genome-scale metabolic modeling is a systems-based approach that attempts to capture the metabolic complexity of the whole cell, for the purpose of gaining insight into metabolic function and regulation. This is achieved by organizing the metabolic components and their corresponding interactions into a single context. The reconstruction process is a challenging and laborious task, especially during the stage of manual curation. For the mouse genome-scale metabolic model, however, we were able to rapidly reconstruct a compartmentalized model from well-curated metabolic databases online. The prototype model was comprehensive. Apart from minor compound naming and compartmentalization issues, only nine additional reactions without gene associations were added during model curation before the model was able to simulate growth in silico. Further curation led to a metabolic model that consists of 1399 genes mapped to 1757 reactions, with a total of 2037 reactions compartmentalized into the cytoplasm and mitochondria, capable of reproducing metabolic functions inferred from literatures. The reconstruction is made more tractable by developing a formal system to update the model against online databases. Effectively, we can focus our curation efforts into establishing better model annotations and gene-protein-reaction associations within the core metabolism, while relying on genome and proteome databases to build new annotations for peripheral pathways, which may bear less relevance to our modeling interest.