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

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.
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Supplementary information: Supplementary data are available at Bioinformatics online.

Source: Bioinformatics - December 28, 2016 Category: Bioinformatics Authors: Marin de Mas, I., Fanchon, E., Papp, B., Kalko, S., Roca, J., Cascante, M. Tags: SYSTEMS BIOLOGY Source Type: research