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Translating Basic Research Into Clinical Practice |

An Integrative Systems Biology Approach to Understanding Pulmonary Diseases

Charles Auffray, PhD; Ian M. Adcock, PhD; Kian Fan Chung, MD; Ratko Djukanovic, MD; Christophe Pison, MD, PhD; Peter J. Sterk, MD, PhD
Author and Funding Information

From the Functional Genomics and Systems Biology for Health (Dr Auffray), CNRS Institute of Biological Sciences, Villejuif, France; the Department of Airways Disease (Drs Adcock and Chung), National Heart and Lung Institute, Imperial College London, London, England; the Southampton NIHR Respiratory Biomedical Research Unit (Dr Djukanovic), University of Southampton School of Medicine, Southampton, England; Fundamental and Applied Bioenergetics (Dr Pison), Inserm U884, Joseph Fourier University of Grenoble, St Martin d’Hères and Pulmonary Division, Grenoble University Hospital, La Tronche, France; and the Department of Respiratory Medicine (Dr Sterk), Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.

Correspondence to: Charles Auffray, Functional Genomics and Systems Biology for Health, CNRS Institute of Biological Sciences, 7 rue Guy Moquet-BP8, 94801 Villejuif cedex, France; e-mail: auffray@vjf.cnrs.fr


The subject of this review was presented by Charles Auffray and Ratko Djukanovic at the ATS 2009 International Conference in San Diego, CA, on May 20, 2009.

Funding/Support: The authors are members of the U-BIOPRED Consortium (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) supported by the Innovative Medicines Initiative (IMI), a partnership between the European Union and the European Federation of Pharmaceutical Industry Associations (EFPIA).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestpubs.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;137(6):1410-1416. doi:10.1378/chest.09-1850
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Chronic inflammatory pulmonary diseases such as COPD and asthma are highly prevalent and associated with a major health burden worldwide. Despite a wealth of biologic and clinical information on normal and pathologic airway structure and function, the primary causes and mechanisms of disease remain to a large extent unknown, preventing the development of more efficient diagnosis and treatment. We propose to overcome these limitations through an integrative systems biology research strategy designed to identify the functional and regulatory pathways that play central roles in respiratory pathophysiology, starting with severe asthma. This approach relies on global genome, transcriptome, proteome, and metabolome data sets collected in cross-sectional patient cohorts with high-throughput measurement platforms and integrated with biologic and clinical data to inform predictive multiscale models ranging from the molecular to the organ levels. Working hypotheses formulated on the mechanisms and pathways involved in various disease states are tested through perturbation experiments using model simulation combined with targeted and global technologies in cellular and animal models. The responses observed are compared with those predicted by the initial models, which are refined to account better for the results. Novel perturbation experiments are designed and tested both computationally and experimentally to arbitrate between competing hypotheses. The process is iterated until the derived knowledge allows a better classification and subphenotyping of severe asthma using complex biomarkers, which will facilitate the development of novel diagnostic and therapeutic interventions targeting multiple components of the molecular and cellular pathways involved. This can be tested and validated in prospective clinical trials.


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