Taking Systems Medicine to Heart

Abstract

<p class="first" id="P1">Systems medicine is a holistic approach to deciphering the complexity of human physiology in health and disease. In essence, a living body is constituted of networks of dynamically interacting units (molecules, cells, organs, etc.) that underlie its collective functions. Declining resilience due to aging and other chronic environmental exposures drives the system to transition from a health state to a disease state; these transitions, triggered by acute perturbations or chronic disturbance, manifest as qualitative shifts in the interactions and dynamics of the disease-perturbed networks. Understanding health-to-disease transitions poses a high-dimensional nonlinear reconstruction problem that requires deep understanding of biology as well as innovation in study design, technology, and data analysis. With a focus on the principles of systems medicine, this Review discusses approaches for deciphering this biological complexity from a novel perspective, namely understanding how disease-perturbed networks function; their study provides insights into fundamental disease mechanisms. The immediate goals for systems medicine are to identify early transitions to cardiovascular (and other chronic) diseases, and to accelerate the translation of new preventive, diagnostic or therapeutic targets into clinical practice, a critical step in the development of personalized, predictive, preventive and participatory (P4) medicine. </p>