Network Medicine and Systems Biology Considerations to Understand Sex Differences in Lung Disease

Abstract

AbstractMen and women have different manifestations of major lung diseases including chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), and pulmonary hypertension. Examples of sex differences in different molecular data types have been observed (genetic, transcriptomic, epigenetic, metabolomic), but few studies have harnessed the power of network medicine and systems biology to unravel the complexity of sex differences in lung disease. Men and women respond differently to environmental exposures, likely capturing both gender (societal constructs) and sex (biologic) effects relevant to the lung. Data collection on gender and gender identity has not been routine in genomic studies but must be performed to develop the most comprehensive precision-based network medicine approaches to lung disease. Each layer contributing to complex networks manifests the aggregate influence of gender- and sex-specific signatures, and these should be systemically evaluated. Many emergent properties and biologic pathways uncovered by sex-specific network analyses would be missed by single omic-type analyses alone. Common approaches in precision medicine have generally not considered sex and gender as key organizing principles. Leveraging “big data” will provide the most advanced insights into sex and gender differences in lung health, resilience, and disease.KeywordsSexGenderGeneticsGenomicsEpigeneticsNetworksNetwork medicineSystems biology