Mathematical Modeling

Integrating bottom-up and top-down Systems Biology

The key is a robust and powerful mathematical modeling method. There are many challenges, including the following issues. (1) Unlike synthetic circuits, which can be designed as isolated as possible to the host, biological circuits can be highly coupled, making it hard to find circuits of the right size to model. (2) A popular way to model a circuit is to use rate equations. However, most of the required kinetic parameters are not directly measurable, especially in vivo. Thus, one has to make either educated guess or fit the parameters against data such as gene expression. This becomes an issue for large circuits with large number of parameters, making this approach prone to overfitting.

A long-standing parameter issue

This parameter problem is a long-standing issue in almost every systems biology studies. Like this famous saying, “with four parameters I can fit an elephant, and with five I can make him wiggle his trunk.”