Sing the possibility that unrecognized biomarkers could be identified through a research approach that predicts functional capacity in this or other similar diseases. Along these lines, Davidsen and colleagues reported their recent findings using a systems biology approach to identify novel factors that promote skeletal muscle dysfunction in COPD 70. They analyzed differences in gene expression profiles in whole lung and hind limb skeletal muscle tissue harvested from swine exposed to chronic hypoxia, chronic cigarette smoke, or a combination of these factors to develop a genome-wide transcriptome (151,072 transcript sequences) relevant to COPD. These data were subjected to enriched KEGG pathway analyses, which, in turn, predicted that the systemic cytokines CXCL10 and CXCL9 may be important markers of dysregulated metabolic function in skeletal muscle in COPD. The investigators confirmed their hypothesis by demonstrating that circulating CXCL10/9 levels are significantly different in plasma from COPD patients as compared to healthy controls, CBIC2MedChemExpress JC-1 providing evidence in support of these factors as potential biomarkers indicative of extrapulmonary end-organ damage in chronic lung disease. The mechanistic underpinnings of lung injury responses have also been addressed using a combination of network biology strategies in order to understand better the pathways resulting in airway remodeling. In a unique experimental design, airway biopsy samples from lungs of patients exposed remotely to sulfur mustard or unexposed controls were subjected to microarray gene expression analysis and combined with genes corresponding to biological factors linked to airway remodeling identified from curated literature searches 71. From these datasets, protein-protein interaction and gene regulatory networks could be synthesized, which were ultimately merged to create functional modules. In that study,HIV-1 integrase inhibitor 2 web Author Manuscript Author Manuscript Author Manuscript Author ManuscriptWiley Interdiscip Rev Syst Biol Med. Author manuscript; available in PMC 2016 July 01.Wang et al.Pagematrix remodeling proteins, particularly matrix metalloproteinase (MMP)-9, were centrally located and well connected within the network. The observation identifying CYP11B1 (11- hydroxylase), STARD10 (steroidogenic acute regulator protein-related lipid transfer protein), and pro-fibrotic proteins (i.e., TGF-) as putative airway remodeling proteins in that analysis was consistent with findings from whole lung transcriptome analysis involving patients with pulmonary arterial hypertension 72. Moreover, these findings are in agreement with data from our laboratory 73 demonstrating activation of steroidogenesis signaling pathways, including aldosterone biosynthesis, in pulmonary vascular cells subjected to chronic hypoxia in vitro and its link to upregulation of TGF– and MMP-dependent signaling pathways that promote pulmonary vascular remodeling. Cancer biology An overarching goal of contemporary cancer therapeutics is the design of personalized drugs to match treatment targets with patients’ particular disease pathobiology. Angiogenesis and cellular plasticity are principal processes implicated in tumor growth, and, therefore, have evolved as the subject of key investigations aiming to identify targets within the framework of this personalized medicine approach. Intrinsic disorder proteins (IDPs) contain unique amino acid sequences that inhibit energetically favorable three-dimensional structures. Relati.Sing the possibility that unrecognized biomarkers could be identified through a research approach that predicts functional capacity in this or other similar diseases. Along these lines, Davidsen and colleagues reported their recent findings using a systems biology approach to identify novel factors that promote skeletal muscle dysfunction in COPD 70. They analyzed differences in gene expression profiles in whole lung and hind limb skeletal muscle tissue harvested from swine exposed to chronic hypoxia, chronic cigarette smoke, or a combination of these factors to develop a genome-wide transcriptome (151,072 transcript sequences) relevant to COPD. These data were subjected to enriched KEGG pathway analyses, which, in turn, predicted that the systemic cytokines CXCL10 and CXCL9 may be important markers of dysregulated metabolic function in skeletal muscle in COPD. The investigators confirmed their hypothesis by demonstrating that circulating CXCL10/9 levels are significantly different in plasma from COPD patients as compared to healthy controls, providing evidence in support of these factors as potential biomarkers indicative of extrapulmonary end-organ damage in chronic lung disease. The mechanistic underpinnings of lung injury responses have also been addressed using a combination of network biology strategies in order to understand better the pathways resulting in airway remodeling. In a unique experimental design, airway biopsy samples from lungs of patients exposed remotely to sulfur mustard or unexposed controls were subjected to microarray gene expression analysis and combined with genes corresponding to biological factors linked to airway remodeling identified from curated literature searches 71. From these datasets, protein-protein interaction and gene regulatory networks could be synthesized, which were ultimately merged to create functional modules. In that study,Author Manuscript Author Manuscript Author Manuscript Author ManuscriptWiley Interdiscip Rev Syst Biol Med. Author manuscript; available in PMC 2016 July 01.Wang et al.Pagematrix remodeling proteins, particularly matrix metalloproteinase (MMP)-9, were centrally located and well connected within the network. The observation identifying CYP11B1 (11- hydroxylase), STARD10 (steroidogenic acute regulator protein-related lipid transfer protein), and pro-fibrotic proteins (i.e., TGF-) as putative airway remodeling proteins in that analysis was consistent with findings from whole lung transcriptome analysis involving patients with pulmonary arterial hypertension 72. Moreover, these findings are in agreement with data from our laboratory 73 demonstrating activation of steroidogenesis signaling pathways, including aldosterone biosynthesis, in pulmonary vascular cells subjected to chronic hypoxia in vitro and its link to upregulation of TGF– and MMP-dependent signaling pathways that promote pulmonary vascular remodeling. Cancer biology An overarching goal of contemporary cancer therapeutics is the design of personalized drugs to match treatment targets with patients’ particular disease pathobiology. Angiogenesis and cellular plasticity are principal processes implicated in tumor growth, and, therefore, have evolved as the subject of key investigations aiming to identify targets within the framework of this personalized medicine approach. Intrinsic disorder proteins (IDPs) contain unique amino acid sequences that inhibit energetically favorable three-dimensional structures. Relati.
