Extracting Insights From Temporal Data by Integrating Dynamic Modeling and Machine Learning

Abstract

Biological processes are dynamic. As a result, temporal analyses are necessary to fully understand the complex interactions that occurs within these systems. One example of a multifaceted biological process is restitution: the initial step in complex wound repair. Restitution is a dynamic process that depends on an elegant orchestration between damaged cells and their intact neighbors. Such orchestration enables the quick repair of the damaged area, which is essential to preserve epithelial integrity and prevent further injury. High quality dynamic data of the cellular and molecular events that make up the gastric restitution process has been documented. However, comprehensive dynamic models that connect all relevant molecular interactions to cellular behaviors are challenging to construct and experimentally validate. In order to efficiently provide feedback to ongoing experimental work, we have integrated dynamical modeling and machine learning to efficiently extract data-driven insights without incorporating detailed mechanisms. Dynamical models convert time course data into a set of static features, which are then subjected to machine learning analysis. The integrated analysis provides data-driven insights into how repair might be regulated in individual gastric organoids. We have provided a "proof of concept" of how such an analysis pipeline can be used to analyze any temporal dataset and provide timely data-driven insights.

Keywords: actin; computational model; gastric epithelium; organoids; restitution.