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An integrative systems biology approach to understanding pulmonary diseases

An integrative systems biology approach to understanding pulmonary diseases
An integrative systems biology approach to understanding pulmonary diseases
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.
0012-3692
1410-1416
Auffray, Charles
16fdf8f6-e7bc-4559-b6b6-d425160867c6
Adcock, Ian M.
427153bc-3b8b-4066-aa4e-5bc41a6c36dd
Chung, Kian Fan
dc062fa0-b6c4-4b03-a0c2-917904e0ea2a
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Pison, Christophe
bfba3ceb-2af8-44b6-bb55-daeebffa24f3
Sterk, Peer J.
7225114a-6103-4f4a-b3e3-afae9d9e55de
Auffray, Charles
16fdf8f6-e7bc-4559-b6b6-d425160867c6
Adcock, Ian M.
427153bc-3b8b-4066-aa4e-5bc41a6c36dd
Chung, Kian Fan
dc062fa0-b6c4-4b03-a0c2-917904e0ea2a
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Pison, Christophe
bfba3ceb-2af8-44b6-bb55-daeebffa24f3
Sterk, Peer J.
7225114a-6103-4f4a-b3e3-afae9d9e55de

Auffray, Charles, Adcock, Ian M., Chung, Kian Fan, Djukanovic, Ratko, Pison, Christophe and Sterk, Peer J. (2010) An integrative systems biology approach to understanding pulmonary diseases. Chest, 137 (6), 1410-1416. (doi:10.1378/chest.09-1850). (PMID:20525651)

Record type: Article

Abstract

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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Published date: June 2010

Identifiers

Local EPrints ID: 185153
URI: http://eprints.soton.ac.uk/id/eprint/185153
ISSN: 0012-3692
PURE UUID: edc4528e-da77-455b-b5a2-566709e2ca65
ORCID for Ratko Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612

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Date deposited: 09 May 2011 14:53
Last modified: 26 Nov 2019 02:07

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