Identification of Hub Genes and Potential Biomarkers for Childhood Asthma by Utilizing an Established Bioinformatic Analysis Approach

Santri, Ichtiarini Nurullita; Irham, Lalu Muhammad; Djalilah, Gina Noor; Perwitasari, Dyah Aryani; Wardani, Yuniar; Phiri, Yohane Vincent Abero; Adikusuma, Wirawan

doi:10.3390/biomedicines10092311

Cited by 11 publications

(3 citation statements)

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“…These include certain HLA family genes, PTPRC, and PTPRJ. These latter two genes are protein tyrosine phosphatases that have been described as master regulators that are differentially expressed in transcriptomic studies of children with severe asthma [34,37]. These genes have also been shown by others to be regulated by DNA methylation and our study is the rst to identify the differential methylation of these genes to be associated with asthma severity.…”

Section: Discussionmentioning

confidence: 63%

Differences in the DNA Methylome of T cells in Adults With Asthma of Varying Severity

Liao,

Cavalcante,

Waller

et al. 2024

Preprint

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Background DNA methylation plays a critical role in asthma development, but differences in DNA methylation among adults with varying asthma severity or asthma endotypes are less well-defined. Objective To examine how DNA methylomic patterns differ among adults with asthma based on asthma severity and airway inflammation. Methods Peripheral blood T cells from 35 adults with asthma in Beijing, China were serially collected over time (130 samples total) and analyzed for global DNA methylation using the Illumina MethylationEPIC Array. Differential methylation was compared among subjects with varying airway inflammation and severity, as measured by fraction of exhaled nitric oxide, forced expiratory volume in one second (FEV1), and Asthma Control Test (ACT) scores. Results Significant differences in DNA methylation were noted among subjects with different degrees of airway inflammation and asthma severity. These differences in DNA methylation were annotated to genes that were enriched in pathways related to asthma or T cell function and included gene ontology categories related to MHC class II assembly, T cell activation, interleukin (IL)-1, and IL-12. Genes related to P450 drug metabolism, glutathione metabolism, and developmental pathways were also differentially methylated in comparisons between subjects with high vs low FEV1 and ACT. Notable genes that were differentially methylated based on asthma severity included RUNX3, several members of the HLA family, AGT, PTPRC, PTPRJ, and several genes downstream of the JAK2 and TNF signaling pathway. Conclusion These findings demonstrate how adults with asthma of varying severity possess differences in peripheral blood T cell DNA methylation that contribute to the phenotype and severity of their overall disease.

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Section: Discussionmentioning

confidence: 63%

Differences in the DNA Methylome of T cells in Adults With Asthma of Varying Severity

Liao,

Cavalcante,

Waller

et al. 2024

Preprint

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show abstract

“…In our study, 10 biomarkers (POSTN, CPA3, CCL26, SERPINB2, CLCA1, TPSAB1, TPSB2, MUC5B, BPIFA1, and CST1) were identified as the highest-ranked hub targets; these findings are in agreement with previous research on hub genes in adult asthma (CPA3, CTSG, POSTN, CLCA1, HDC, and MUC5B) [ 23 ]. In addition, interleukins, especially IL6 and IL4, were suggested as prospective biomarkers of childhood asthma [ 24 ]. Such findings will enable us to better understand the occurrence of asthma.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic Analysis of Key Regulatory Genes in Adult Asthma and Prediction of Potential Drug Candidates

et al. 2023

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Asthma is a common chronic disease that is characterized by respiratory symptoms including cough, wheeze, shortness of breath, and chest tightness. The underlying mechanisms of this disease are not fully elucidated, so more research is needed to identify better therapeutic compounds and biomarkers to improve disease outcomes. In this present study, we used bioinformatics to analyze the gene expression of adult asthma in publicly available microarray datasets to identify putative therapeutic molecules for this disease. We first compared gene expression in healthy volunteers and adult asthma patients to obtain differentially expressed genes (DEGs) for further analysis. A final gene expression signature of 49 genes, including 34 upregulated and 15 downregulated genes, was obtained. Protein–protein interaction and hub analyses showed that 10 genes, including POSTN, CPA3, CCL26, SERPINB2, CLCA1, TPSAB1, TPSB2, MUC5B, BPIFA1, and CST1, may be hub genes. Then, the L1000CDS2 search engine was used for drug repurposing studies. The top approved drug candidate predicted to reverse the asthma gene signature was lovastatin. Clustergram results showed that lovastatin may perturb MUC5B expression. Moreover, molecular docking, molecular dynamics simulation, and computational alanine scanning results supported the notion that lovastatin may interact with MUC5B via key residues such as Thr80, Thr91, Leu93, and Gln105. In summary, by analyzing gene expression signatures, hub genes, and therapeutic perturbation, we show that lovastatin is an approved drug candidate that may have potential for treating adult asthma.

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“…These networks incorporate hemorrhoid-associated genes from diverse databases, providing valuable understanding of the genetic foundation of hemorrhoids, and proposing encouraging implications for the detection of feasible diagnostic biomarkers and improved therapeutic approaches. The detection of novel biomarkers is critical for classifying patients, foretelling therapeutic responses, and evaluating prognosis ( Santri et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated genomic network analysis revealed potential of a druggable target for hemorrhoid treatment

Adikusuma,

Firdayani,

Irham

et al. 2023

Saudi Pharmaceutical Journal

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Identification of Hub Genes and Potential Biomarkers for Childhood Asthma by Utilizing an Established Bioinformatic Analysis Approach

Cited by 11 publications

References 50 publications

Differences in the DNA Methylome of T cells in Adults With Asthma of Varying Severity

Differences in the DNA Methylome of T cells in Adults With Asthma of Varying Severity

Bioinformatic Analysis of Key Regulatory Genes in Adult Asthma and Prediction of Potential Drug Candidates

Integrated genomic network analysis revealed potential of a druggable target for hemorrhoid treatment

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