It’s about time: Analysing simplifying assumptions for modelling multi-step pathways in systems biology

by Niklas Korsbo, Henrik Jönsson

Thoughtful use of simplifying assumptions is crucial to make systems biology models tractable while still representative of the underlying biology. A useful simplification can elucidate the core dynamics of a system. A poorly chosen assumption can, however, either render a model too complicated for making conclusions or it can prevent an otherwise accurate model from describing experimentally observed dynamics. Here, we perform a computational investigation of sequential multi-step pathway models that contain fewer pathway steps than the system they are designed to emulate. We demonstrate when such models will fail to reproduce data and how detrimental truncation of a pathway leads to detectable signatures in model dynamics and its optimised parameters. An alternative assumption is suggested for simplifying such pathways. Rather than assuming a truncated number of pathway steps, we propose to use the assumption that the rates of information propagation along the pathway is homogeneous and, instead, letting the length of the pathway be a free parameter. We first focus on linear pathways that are sequential and have first-order kinetics, and we show how this assumption results in a three-parameter model that consistently outperforms its truncated rival and a delay differential equation alternative in recapitulating observed dynamics. We then show how the proposed assumption allows for similarly terse and effective models of non-linear pathways. Our results provide a foundation for well-informed decision making during model simplifications.

Make more money selling and advertising your products and services for free on Ominy market. Click here to start selling now

Paper source
Plos Journal

READ MORE  NOX5-induced uncoupling of endothelial NO synthase is a causal mechanism and theragnostic target of an age-related hypertension endotype

Ominy science editory team

A team of dedicated users that search, fetch and publish research stories for Ominy science.

Enable notifications of new posts OK No thanks