From Pharmacogenomics and Systems Biology to Personalized Care: A Framework of Systems and Dynamical Medicine

Abstract

With the integration of pharmacogenomics and systems biology, personalized medicine would be possible by switching the gear from the reductionism-based and disease-focused medical system toward a dynamical systems-based and human-centric health care. Comprehensive models are needed to represent the properties of complex adaptive systems (CASs) to elucidate the complexity in health and diseases, including the features of emergence, nonlinearity, self-organization, and adaptation. As all diseases have the dynamical elements, nonlinear time-series analyses are necessary to characterize the system dynamics at various levels to elucidate the physiological and pathological rhythms, oscillations, and feedback loops. Such analyses can help detect patterns across multiple scales in both the spatial (e.g., from molecules to cells, from organisms to psychosocial environments) and the temporal (e.g., from nanoseconds to hours, from years to decades) dimensions. Based on such understanding, systems and dynamical medicine can be developed with the emphasis on the whole systems that change over time to address the nonlinearity and interconnectivity toward a holistic and proactive care. Accurate and robust biomarkers with predictive values can be discovered to reflect the systemic conditions and disease stages. Network and dynamical models may support individualized risk analysis, presymptomatic diagnosis, precise prognosis, and integrative interventions. Systems and dynamical medicine may provide the root for the achievement of predictive, preventive, personalized, and participatory (P4) medicine.

Toward Dynamical Systems Medicine: Personalized and Preventive Strategies

“…Such interconnections also address the concept of 'nonlinearity', as many interactions do not have linear results. For instance, the continuous increase of drug dosages may lead to serious adverse effects but not better outcomes [1]. Embracing these concepts of CASs in personalized medicine would facilitate clinical practice "to bring the right interventions to the right people with the right dosages and intensities at the right time" [1].…”

“…Toward dynamical systems medicine: personalized & preventive strategies Editorial profiling from molecules to organisms, from nanoseconds to seasons [1]. The highlight of the word 'systems' in medicine may address the 'roots' of health and diseases including the attributes of emergence, nonlinearity and self-organization.…”

“…In addition, 'self-organization' and 'robustness' are the essential features of living CASs for maintaining homeostasis and disease healing [1]. The applications of such concepts can concentrate on promoting the self-adjustment of abnormal functions, rather than simply 'winning' the wars on diseases by killing viruses or cancer cells that often results in adverse reactions.…”

“…The focus of the relevant treatments would be promoting the abilities of self-regulation toward normal neuroimmune functions to relieve the oxidative-inflammatory conditions. Furthermore, the self-organization and robust activities may affect the interactions among different system levels [1]. The hierarchically organized networks are composed of interconnected genes, cells, tissues, organs, individuals and populations [6].…”

Early Prediction of Patient Mortality Based on Routine Laboratory Tests and Predictive Models in Critically Ill Patients

“…Precision medicine is based on comprehensive models with the potential to elucidate the complexity of health and diseases, including the features of emergence, nonlinearity, selforganization, and adaptation [1].…”