An integrative analysis to distinguish between emphysema (EML) and alpha-1 antitrypsin deficiency-related emphysema (ADL)-A systems biology approach

Lung Emphysema is an abnormal enlargement of the air sacs followed by the destruction of alveolar walls without any prominent fibrosis. This study primarily identifies the differentially expressed genes (DEGs), interactions between them, and their significant involvement in the activated signaling cascades. The dataset with ID GSE1122 (five normal lung tissue samples, five of usual emphysema, and five of alpha-1 antitrypsin deficiency-related emphysema) from the gene expression omnibus (GEO) was analyzed using the GEO2R tool. The physical association between the DEGs were mapped using the STRING tool and was visualized in the Cytoscape software. The enriched functional processes were identified with the ClueGO plugin's help from Cytoscape. Further integrative functional annotation was performed by implying the GeneGo Metacore to distinguish the enriched pathway maps, process networks, and GO processes. The results from this analysis revealed the critical signaling cascades that have been either activated or inhibited due to identified DEGs. We found the activated pathways such as immune response IL-1 signaling pathway, positive regulation of smooth muscle migration, BMP signaling pathway, positive regulation of leukocyte migration, NIK/NF-kappB signaling, and cytochrome-c oxidase activity. Finally, we mapped four crucial genes (CCL5, ALK, TAC1, CD74, and HLA-DOA) by comparing the functional annotations that could be significantly influential in emphysema molecular pathogenesis. Our study provides insights into the pathogenesis of emphysema and helps in developing potential drug targets against emphysema. 2021 Elsevier Inc.Mr. Udhaya Kumar. S, one of the authors, gratefully acknowledges the Indian Council of Medical Research (ICMR), India, for providing him a Senior Research Fellowship [ISRM/11(93)/2019]. The authors would like to thank the Vellore Institute of Technology, India, and Qatar University, Qatar, for providing the necessary research facilities and encouragement to carry out this work. The authors have declared that no conflicts of interest exist. UKS, HZ, and GPDC, contributed to designing the study and data acquisition, analysis, and interpretation. UKS, TKD, MPN, VAP, VK, DN, SY, and MR are involved in the acquisition, analysis, and interpreting of the results. UKS, MPN, TKD, MR, VAP, VK, DN, SY, and CGPD contributed to data interpretation, conducted, and drafting the manuscript. CGPD and HZ supervised the entire study and studied, acquiring, analyzing, understanding the data, and drafting the manuscript. The manuscript was reviewed and approved by all the authors. No funding agency is involved in the present study.Scopu