Molecular mechanisms underlying COPD-muscle dysfunction unveiled through a systems medicine approach. (6th October 2016)

• Record Type: Journal Article
• Authors: Marín de Mas, Igor; Fanchon, Eric; Papp, Balázs; Kalko, Susana; Roca, Josep; Cascante, Marta
• Is Part Of: Bioinformatics. Volume 33:Number 1(2017)
• Page Start: 95
• Page End: 103
• Publication Date: 2016-10-06
• Subjects: Bioinformatics -- Periodicals; Genomics -- Data processing -- Periodicals; Computational biology -- Periodicals; 572.80285
• DOI: 10.1093/bioinformatics/btw566
• Languages: English
• ISSNs: 1367-4803

Abstract

Abstract : Motivation: Skeletal muscle dysfunction is a systemic effect in one-third of patients with chronic obstructive pulmonary disease (COPD), characterized by high reactive-oxygen-species (ROS) production and abnormal endurance training-induced adaptive changes. However, the role of ROS in COPD remains unclear, not least because of the lack of appropriate tools to study multifactorial diseases. Results: We describe a discrete model-driven method combining mechanistic and probabilistic approaches to decipher the role of ROS on the activity state of skeletal muscle regulatory network, assessed before and after an 8-week endurance training program in COPD patients and healthy subjects. In COPD, our computational analysis indicates abnormal training-induced regulatory responses leading to defective tissue remodeling and abnormal energy metabolism. Moreover, we identified tnf, insr, inha and myc as key regulators of abnormal training-induced adaptations in COPD. The tnf-insr pair was identified as a promising target for therapeutic interventions. Our work sheds new light on skeletal muscle dysfunction in COPD, opening new avenues for cost-effective therapies. It overcomes limitations of previous computational approaches showing high potential for the study of other multi-factorial diseases such as diabetes or cancer. Contact: [e-mail] or [e-mail] Supplementary information: Supplementary data are available at Bioinformatics online.