SALARECON connects the Atlantic salmon genome to growth and feed efficiency.

Atlantic salmon (Salmo salar) is the most valuable farmed fish globally and there is much interest in optimizing its genetics and rearing conditions for growth and feed efficiency. Marine feed ingredients must be replaced to meet global demand, with challenges for fish health and sustainability. Metabolic models can address this by connecting genomes to metabolism, which converts nutrients in the feed to energy and biomass, but such models are currently not available for major aquaculture species such as salmon. We present SALARECON, a model focusing on energy, amino acid, and nucleotide metabolism that links the Atlantic salmon genome to metabolic fluxes and growth. It performs well in standardized tests and captures expected metabolic (in)capabilities. We show that it can explain observed hypoxic growth in terms of metabolic fluxes and apply it to aquaculture by simulating growth with commercial feed ingredients. Predicted limiting amino acids and feed efficiencies agree with data, and the model suggests that marine feed efficiency can be achieved by supplementing a few amino acids to plant- and insect-based feeds. SALARECON is a high-quality model that makes it possible to simulate Atlantic salmon metabolism and growth. It can be used to explain Atlantic salmon physiology and address key challenges in aquaculture such as development of sustainable feeds.

Extracting functionally accurate context-specific models of Atlantic salmon metabolism.

Constraint-based models (CBMs) are used to study metabolic network structure and function in organisms ranging from microbes to multicellular eukaryotes. Published CBMs are usually generic rather than context-specific, meaning that they do not capture differences in reaction activities, which, in turn, determine metabolic capabilities, between cell types, tissues, environments, or other conditions. Only a subset of a CBM's metabolic reactions and capabilities are likely to be active in any given context, and several methods have therefore been developed to extract context-specific models from generic CBMs through integration of omics data. We tested the ability of six model extraction methods (MEMs) to create functionally accurate context-specific models of Atlantic salmon using a generic CBM (SALARECON) and liver transcriptomics data from contexts differing in water salinity (life stage) and dietary lipids. Three MEMs (iMAT, INIT, and GIMME) outperformed the others in terms of functional accuracy, which we defined as the extracted models' ability to perform context-specific metabolic tasks inferred directly from the data, and one MEM (GIMME) was faster than the others. Context-specific versions of SALARECON consistently outperformed the generic version, showing that context-specific modeling better captures salmon metabolism. Thus, we demonstrate that results from human studies also hold for a non-mammalian animal and major livestock species.