A new computational workflow to guide personalized drug therapy

Objective: Computational models are at the forefront of the pursuit of personalized medicine thanks to their descriptive and predictive abilities. In the presence of complex and heterogeneous data, patient stratification is a prerequisite for effective precision medicine, since disease development is often driven by individual variability and unpredictable environmental events. Herein, we present GreatNector workflow as a valuable tool for (i) the analysis and clustering of patient-derived longitudinal data, and (ii) the simulation of the resulting model of patient-specific disease dynamics.Methods: GreatNectoris designed by combining an analytic strategy composed of CONNECTOR, a data-driven framework for the inspection of longitudinal data, and an unsupervised methodology to stratify the subjects with GreatMod, a quantitative modeling framework based on the Petri Net formalism and its generalizations. Results: To illustrate GreatNectorcapabilities, we exploited longitudinal data of four immune cell populations collected from Multiple Sclerosis patients. Our main results report that the T-cell dynamics after alemtuzumab treatment separate non-responders versus responders patients, and the patients in the non-responders group are characterized by an increase of the Th17 concentration around 36 months.Conclusion: GreatNectoranalysis was able to stratify individual patients into three model meta-patients whose dynamics suggested insight into patient-tailored interventions.

Automated summary

GreatNector workflow is a valuable tool for analyzing and clustering patient-derived longitudinal data, as well as simulating the resulting model of patient-specific disease dynamics. The analysis was able to stratify individual patients into three model meta-patients, providing insight into patient-tailored interventions. The results showed that T-cell dynamics after alemtuzumab treatment separate non-responders versus responders patients, with non-responders group characterized by an increase of the Th17 concentration around 36 months.