Decoding the Role of Sphingosine-1-Phosphate in Asthma and Other Respiratory System Diseases Using Next Generation Knowledge Discovery Platforms Coupled With Luminex Multiple Analyte Profiling Technology

Abstract

Sphingosine-1-phosphate (S1P) is a pleiotropic sphingolipid derived by the phosphorylation of sphingosine either by sphingosine kinase 1 (SPHK1) or SPHK2. Importantly, S1P acts through five different types of G-protein coupled S1P receptors (S1PRs) in immune cells to elicit inflammation and other immunological processes by enhancing the production of various cytokines, chemokines, and growth factors. The airway inflammation in asthma and other respiratory diseases is augmented by the activation of immune cells and the induction of T-helper cell type 2 (Th2)-associated cytokines and chemokines. Therefore, studying the S1P mediated signaling in airway inflammation is crucial to formulate effective treatment and management strategies for asthma and other respiratory diseases. The central aim of this study is to characterize the molecular targets induced through the S1P/S1PR axis and dissect the therapeutic importance of this key axis in asthma, airway inflammation, and other related respiratory diseases. To achieve this, we have adopted both high throughput next-generation knowledge discovery platforms such as SwissTargetPrediction, WebGestalt, Open Targets Platform, and Ingenuity Pathway Analysis (Qiagen, United States) to delineate the molecular targets of S1P and further validated the upstream regulators of S1P signaling using cutting edge multiple analyte profiling (xMAP) technology (Luminex Corporation, United States) to define the importance of S1P signaling in asthma and other respiratory diseases in humans.

Unraveling the Catha edulis Extract Effects on the Cellular and Molecular Signaling in SKOV3 Cells

“…WebGestalt (wGSEA) is an open-source platform ( http://webgestalt.org/ ) that facilitates a more flexible, comprehensive, and interactive functional enrichment analysis of differentially expressed proteins (DEPs) or differentially expressed genes (DEGs) ( Liao et al, 2019 ). The newest version of the wGSEA identifies 155,175 functional groups, 342 gene identifiers, and 12 major organisms with an additional option for including user-defined functional databases ( Liao et al, 2019 ; Bahlas et al, 2020 ). The DEPs or DEGs derived from medium- to large-scale omics experiments can be classified based on biological, molecular, and cellular functions using the wGSEA web tool.…”

“…The DEPs or DEGs derived from medium- to large-scale omics experiments can be classified based on biological, molecular, and cellular functions using the wGSEA web tool. To functionally classify the cathine- and cathinone-induced putative protein targets, the Over Representation Analysis (ORA) module of the wGSEA was chosen ( Supplementary Figure S1 ) , the preferred organism was Homo sapiens , and gene ontology (biological, cellular, and molecular functions) and disease databases such as OMIM, GLAD4U, and DisGeNET were selected for further downstream analyses ( Liao et al, 2019 ; Bahlas et al, 2020 ). The default parameters for the enrichment analysis such as the minimum number of IDs (5), the maximum number of IDs (2000), the Benjamini Hochberg (BH) method for computing the False Discovery (FDR) Rate ( p < 0.05), and the significance level (Top 10) were applied for each wGSEA analysis ( Bahlas et al, 2020 ).…”

“…Ingenuity Pathway Analysis (IPA) software (Qiagen Inc., MD, United States) has a cutting edge, up to date next generation knowledge base that consists of clarified scientific information from publications, databases, and other relevant resources ( Jafri et al, 2019 ; Bahlas et al, 2020 ). Here, we applied the IPA to functionally annotate the protein clusters and identified biologically significant disease-specific pathways regulated by cathine and cathinone molecular targets.…”

Deciphering Novel SARS CoV-2 specific Disease Pathways from RNA Sequencing Data of COVID-19 Infected A549 Cells and Potential Therapeutics using Next Generation Knowledge Discovery Platforms

“…Isomeric Simpli ed Molecular Input Line Entry System (SMILES) codes of Prednisolone and Withaferin-A was used in the SwissTargetPrediction tool to nd the protein targets (Bahlas et al, 2020). The ligand-based target prediction for both prednisolone and Withaferin-A was performed as described before (Bahlas et al, 2020;Kalamegam et al, 2020).…”

“…In the present study, the SwissTargetPrediction was performed for Prednisolone and Withaferin A using the canonical SMILES code. The Open Targets Platform was applied to uncover the Withaferin-A molecular targets associated with COVID-19 disease pathology (Bahlas et al, 2020;Carvalho-Silva et al, 2019;Koscielny et al, 2017). The scienti c evidence was used in the Open Targets Platform to assign a score and rank target-disease associations and help target prioritization (Carvalho-Silva et al, 2019) .…”