Identification of Prognostic Genes Associated with Asthma in Pakistan
Identification of Prognostic Genes Associated with Asthma in Pakistan
Faiza Naeem1, Muhammad Farooq Sabar1, Muhammad Usman Ghani2,*, Qurat Ul Ain1 and Qurat-ul-Ain Zafar1
ABSTRACT
Asthma is a severe bronchial inflammatory disorder with high prevalence. In the current study, a list of significantly asthma-associated genes was created to identify asthma-associated pathways and ranking of genes based on protein interactions and centrality-lethality hypothesis representing that knockdown of influential node and edge leads toward the development of the disease. This ranking allows identification of the influential protein for the targeted drug discovery and therapies. An extensive study of published articles was conducted to enlist asthma-associated genes reported significant (P-value < 0.05) in the Pakistani population. Pathway Connector (http://bioinformatics.cing.ac.cy/PathwayConnector) was used to analyze the pathways associated with genes as well as novel pathways through complimentary network analysis. Protein-protein interaction studies were conducted using String (https://string-db.org/) and genes were ranked on a centrality score basis using Cytoscape (https://cytoscape.org/index.html). IL4, IL13, IL10, IL27, ADAM33, TBXA2R, FCER1β, ORMDL3, IKZF3, LRRC3C, GSDMA, GSTP1, GC, STAT6, CD14 and ACE are asthma-associated genes, significantly reported in the Pakistani population. Pathway-connector provided a network of forty-six pathways and their complimentary-analysis provided thirteen new pathways including (hsa04658) Th1/Th2 and (hsa04659) Th17 cell differentiation pathways having STAT6, IL4, and IL13 genes having contribution in asthma. A network of appropriately matched proteins was provided by the string that was further utilized for centrality-measurement which ranked the thirteen most persuasive genes from top to bottom as IL10, IL4, ORMDL3, IL13, MS4A2, ADAM33, STAT6, GSDMA, IKZF3, LRRC3C, IL27, CD14, and ACE. This study enlightens the significantly associated asthma genes in the Pakistani population, figures out influential asthma linked pathways, and ranking of influential genes predicting their role in targeted drug discovery and therapies.
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