Molecular mechanisms underlying COPD-muscle dysfunction unveiled through a systems medicine approach

Marin de Mas, I. and Fanchon, E. and Papp, Balázs and Kalko, S. and Roca, J. (2017) Molecular mechanisms underlying COPD-muscle dysfunction unveiled through a systems medicine approach. BIOINFORMATICS, 33 (1). pp. 95-103. ISSN 1367-4803

Text deMasBioinformatics.pdf Restricted to Registered users only Download (758kB)

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: jroca@clinic.ub.es or martacascante@ub.eduSupplementary information: Supplementary data are available at Bioinformatics online.

Actions (login required)

Edit Item