Abstract
Heterogeneity among individual patients presents a fundamental challenge to effective treatment, since a treatment protocol working for a portion of the population often fails in others. We hypothesize that a computational pipeline integrating mathematical modeling and machine learning could be used to address this fundamental challenge and facilitate the optimization of individualized treatment protocols. We tested our hypothesis with the neuroendocrine systems controlled by the hypothalamic-pituitary-adrenal (HPA) axis. With a synergistic combination of mathematical modeling and machine learning (ML), this integrated computational pipeline could indeed efficiently reveal optimal treatment targets that significantly contribute to the effective treatment of heterogeneous individuals. What is more, the integrated pipeline also suggested quantitative information on how these key targets should be perturbed. Based on such ML revealed hints, mathematical modeling could be used to rationally design novel protocols and test their performances. We believe that this integrated computational pipeline, properly applied in combination with other computational, experimental and clinical research tools, can be used to design novel and improved treatment against a broad range of complex diseases.