title: Signaling network of lipids as a comprehensive scaffold for omics data integration in sputum of COPD patients.
abstract: Chronic obstructive pulmonary disease (COPD) is a heterogeneous and progressive inflammatory condition that has been linked to the dysregulation of many metabolic pathways including lipid biosynthesis. How lipid metabolism could affect disease progression in smokers with COPD remains unclear. We cross-examined the transcriptomics, proteomics, metabolomics, and phenomics data available on the public domain to elucidate the mechanisms by which lipid metabolism is perturbed in COPD. We reconstructed a sputum lipid COPD (SpLiCO) signaling network utilizing active/inactive, and functional/dysfunctional lipid-mediated signaling pathways to explore how lipid-metabolism could promote COPD pathogenesis in smokers. SpLiCO was further utilized to investigate signal amplifiers, distributers, propagators, feed-forward and/or -back loops that link COPD disease severity and hypoxia to disruption in the metabolism of sphingolipids, fatty acids and energy. Also, hypergraph analysis and calculations for dependency of molecules identified several important nodes in the network with modular regulatory and signal distribution activities. Our systems-based analyses indicate that arachidonic acid is a critical and early signal distributer that is upregulated by the sphingolipid signaling pathway in COPD, while hypoxia plays a critical role in the elevated dependency to glucose as a major energy source. Integration of SpLiCo and clinical data shows a strong association between hypoxia and the upregulation of sphingolipids in smokers with emphysema, vascular disease, hypertension and those with increased risk of lung cancer.
authors.affiliation: Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. Electronic address: azimzadeh@nigeb.ac.ir.
authors.forename: Sadegh
authors.initials: S
authors.lastname: Azimzadeh Jamalkandi
authors.affiliation: Department of Computational Biology, Faculty of High Technologies, Tarbiat Modares University, Tehran, Iran; School of Biological Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran. Electronic address: mirzaie@modares.ac.ir.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mirzaie
authors.affiliation: Protein Chemistry and Proteomics Unit, Biotechnology research Center, Pasteur Institute of Iran, Tehran, Iran. Electronic address: m_jafari@pasteur.ac.ir.
authors.forename: Mohieddin
authors.initials: M
authors.lastname: Jafari
authors.affiliation: Proteomics Laboratory, Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. Electronic address: hosseinmehrani@ymail.com.
authors.forename: Hossein
authors.initials: H
authors.lastname: Mehrani
authors.affiliation: Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. Electronic address: parvinshariati@yahoo.com.
authors.forename: Parvin
authors.initials: P
authors.lastname: Shariati
authors.affiliation: Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. Electronic address: saba@nigeb.ac.ir.
authors.forename: Mahvash
authors.initials: M
authors.lastname: Khodabandeh
mesh_terms: D016208:Databases, Factual; D005260:Female; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects / Q000235:genetics / Q000378:metabolism; D013107:Sphingolipids / Q000235:genetics / Q000378:metabolism; D013183:Sputum / Q000378:metabolism*
chemical_list: D013107:Sphingolipids
keywords: COPD; Chronic obstructive pulmonary disease; Data integration; Lipid; Multi-layer; Multi-omics; Network analysis