Systems medicine and integrated care to combat chronic noncommunicable diseases

Jean Bousquet, Josep M Anto, Peter J Sterk, Ian M Adcock, Kian Fan Chung, Josep Roca, Alvar Agusti, Chris Brightling, Anne Cambon-Thomsen, Alfredo Cesario, Sonia Abdelhak, Stylianos E Antonarakis, Antoine Avignon, Andrea Ballabio, Eugenio Baraldi, Alexander Baranov, Thomas Bieber, Joël Bockaert, Samir Brahmachari, Christian Brambilla, Jacques Bringer, Michel Dauzat, Ingemar Ernberg, Leonardo Fabbri, Philippe Froguel, David Galas, Takashi Gojobori, Peter Hunter, Christian Jorgensen, Francine Kauffmann, Philippe Kourilsky, Marek L Kowalski, Doron Lancet, Claude Le Pen, Jacques Mallet, Bongani Mayosi, Jacques Mercier, Andres Metspalu, Joseph H Nadeau, Grégory Ninot, Denis Noble, Mehmet Oztürk, Susanna Palkonen, Christian Préfaut, Klaus Rabe, Eric Renard, Richard G Roberts, Boleslav Samolinski, Holger J Schünemann, Hans-Uwe Simon, Marcelo Bento Soares, Giulio Superti-Furga, Jesper Tegner, Sergio Verjovski-Almeida, Peter Wellstead, Olaf Wolkenhauer, Emiel Wouters, Rudi Balling, Anthony J Brookes, Dominique Charron, Christophe Pison, Zhu Chen, Leroy Hood, Charles Auffray, Jean Bousquet, Josep M Anto, Peter J Sterk, Ian M Adcock, Kian Fan Chung, Josep Roca, Alvar Agusti, Chris Brightling, Anne Cambon-Thomsen, Alfredo Cesario, Sonia Abdelhak, Stylianos E Antonarakis, Antoine Avignon, Andrea Ballabio, Eugenio Baraldi, Alexander Baranov, Thomas Bieber, Joël Bockaert, Samir Brahmachari, Christian Brambilla, Jacques Bringer, Michel Dauzat, Ingemar Ernberg, Leonardo Fabbri, Philippe Froguel, David Galas, Takashi Gojobori, Peter Hunter, Christian Jorgensen, Francine Kauffmann, Philippe Kourilsky, Marek L Kowalski, Doron Lancet, Claude Le Pen, Jacques Mallet, Bongani Mayosi, Jacques Mercier, Andres Metspalu, Joseph H Nadeau, Grégory Ninot, Denis Noble, Mehmet Oztürk, Susanna Palkonen, Christian Préfaut, Klaus Rabe, Eric Renard, Richard G Roberts, Boleslav Samolinski, Holger J Schünemann, Hans-Uwe Simon, Marcelo Bento Soares, Giulio Superti-Furga, Jesper Tegner, Sergio Verjovski-Almeida, Peter Wellstead, Olaf Wolkenhauer, Emiel Wouters, Rudi Balling, Anthony J Brookes, Dominique Charron, Christophe Pison, Zhu Chen, Leroy Hood, Charles Auffray

Abstract

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.

Figures

Figure 1
Figure 1
NCDs are associated with complex gene-environment interactions modulated by socio-economic determinants, psychological factors, age and gender. The products of these interactions lead to the biological expression of NCDs and further to their clinical expression with co-morbidities. A new definition of NCD phenotypes is needed to understand how a network of molecular and environmental factors can lead to complex clinical outcomes of NCDs for prevention and control.
Figure 2
Figure 2
Classical phenotypes are based on a priori ontologies (cardiovascular disease, chronic obstructive pulmonary disease (COPD) and type 2 diabetes), and new phenotypes are based on statistical modeling of all the complex components of NCD onset, persistence and prognosis.
Figure 3
Figure 3
The concept of a uniform definition for NCD severity is based on control, responsiveness to treatment and risks (short, medium and long term). A single flow chart is proposed to define severity to improve phenotype characterization for all purposes (research, clinical and public health). It is based on diagnosis, therapeutic interventions and their availability/affordability, risk factors and co-morbidities.
Figure 4
Figure 4
Iterative mathematical modeling to increase knowledge on NCDs. Various targeted or comprehensive data types are collected from samples of individuals with carefully defined phenotypes, processed using probabilistic and network analysis tools, and integrated into predictive models using a knowledge management and simulation platform, leading to the refinement of the classification of NCDs. Mechanistic hypotheses and complex biomarkers of NCDs generated through this process are then tested and validated iteratively using small then large cohorts of independent samples, providing potential diagnostic and therapeutic solutions for the general population.

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