Why are genome-scale models needed?

Written by Sandra Gomez Romero

Think about pets. Many people around you may have cats or dogs. Both cats and dogs need food to live, and this food has proteins, carbohydrates, fats, and vitamins that provide a nutritious diet for your pet. Even though both cats and dogs need proteins, fats, and vitamins to live a healthy life, they need different proportions of these nutrients. A cat shouldn't regularly eat dog food because, over time, their nutritional needs won't be met, which could affect their health. Additionally, even though all dogs share some nutritional requirements, they vary among dogs based on their size, age, and breed. 

Cells are the same. Even though most mammalian cells can be maintained using some common cell culture media as baseline (DMEM, Ham's F10, RPMI, etc.), these formulations must be modified depending on the species of origin and cell type. Ideally, every cell line should undergo a media optimization process to identify the optimal amino acid composition, glucose concentration, transcription factors, and vitamins that support their growth.

Currently, cell culture media optimization is done by creating many experiments where one parameter is modified at a time. For example, an array of experiments may measure which starting concentration of glucose is ideal for the cells. However, this approach is blind to the mechanism driving this cellular need, and it is costly because it requires large amounts of reagents, labor, and time to create the needed combinations.

Genome-scale models summarize all the genes in a cell and all the reactions in the cell. In this way, genome-scale models offer a bird ' s-eye view to understand how the different parts of the cell drive the nutritional requirements of the cell. 

Using genome-scale models, we can optimize and customize cell culture media for each cell type using a data-driven approach. Genome-scale models can be used to output the ideal amino acid, glucose, vitamins, and transcription factor concentrations for each cell line. Once the starting model for a species is created, these models can be modified to create customized models for each cell line, thus simplifying the cell culture media design process once the model is created for a species.

Using our pet example from above, a genome-scale model would help us create the general diet guidelines that all dog food needs. Using these guidelines as a starting point, we can then customize the model to create new formulations for different breeds and ages. In this way, the initial model can be tweaked to make food for chihuahuas, German shepherds, and senior dogs using a model-guided approach. This approach saves time and money.