Transparency in metabolic network reconstruction enables scalable biological discovery

Reconstructing metabolic pathways has long been a focus of active research. Now, draft models can be generated from genomic annotation and used to simulate metabolic fluxes of mass and energy at the whole-cell scale. This approach has led to an explosion in the number of functional metabolic network models. However, more models have not led to expanded coverage of metabolic reactions known to occur in the biosphere. Thus, there exists opportunity to reconsider the process of reconstruction and model derivation to better support the less-scalable investigative processes of biocuration and experimentation. Realizing this opportunity to improve our knowledge of metabolism requires developing new tools that make reconstructions more useful by highlighting metabolic network knowledge limitations to guide future research.