Altered DNA methylation pattern contributes to differential epigenetic immune signaling in the upper respiratory airway of COVID-19 patients DOI
Melissa Govender, Jyotirmoy Das, Francis R. Hopkins

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 30, 2024

Abstract The emergence of SARS-CoV-2 has had a profound adverse impact on global health and continues to remain threat worldwide. disease spectrum COVID-19 ranges from asymptomatic fatal clinical outcomes especially in the elderly population individuals with underlying medical conditions. host immune responses cells at protein DNA levels remains largely ambiguous. In case-control study, here we explored methylation patterns upper respiratory airway determine how infection altered status requiring hospitalization for COVID-19. We performed arrays nasopharyngeal swabs inclusion/hospitalization as well 6 weeks post-inclusion. Our study reveals distinct pattern patients compared healthy controls, characterized by 317 779 differentially methylated CpGs. Notably, within transcription start sites gene body, exhibited higher number genes/CpGs elevated levels. Enrichment analysis genes highlighted associated inflammatory functions. Some -induced CpG methylations were transient, returning normal Enriched interest included IL-17A, pivotal cytokine implicated inflammation healing, NUP93, antiviral innate immunity. Further, six our data set, OAS1, CXCR5, APP, CCL20, CNR2, C3AR1, found enrichment previous studies. Additionally, RNAse1 RNAse2 emerged key regulators, while IL-18 played role various biological processes patients. Overall, results demonstrates that major modifying many this could have implications conditioning airways individual response future infections.

Language: Английский

Next generation sequencing-based transcriptome data mining for virus identification and characterization: review on recent progress and prospect DOI Creative Commons

Mohammadreza Rahimian,

Bahman Panahi

Journal of Clinical Virology Plus, Journal Year: 2024, Volume and Issue: unknown, P. 100194 - 100194

Published: Sept. 1, 2024

Language: Английский

Citations

5
Boosting edgeR (Robust) by dealing with missing observations and gene-specific outliers in RNA-Seq profiles and its application to explore biomarker genes for diagnosis and therapies of ovarian cancer DOI Creative Commons
Bandhan Sarker, Md. Matiur Rahaman, Muhammad Habibulla Alamin

et al.

Genomics, Journal Year: 2024, Volume and Issue: 116(3), P. 110834 - 110834

Published: March 26, 2024

The edgeR (Robust) is a popular approach for identifying differentially expressed genes (DEGs) from RNA-Seq profiles. However, it shows weak performance against gene-specific outliers and unable to handle missing observations. To address these issues, we proposed pre-processing of count data by combining the iLOO-based outlier detection random forest-based imputation boosting (Robust). Both simulation real analysis results showed that outperformed conventional investigate effectiveness identified DEGs diagnosis, therapies ovarian cancer (OC), selected top-ranked 12 (IL6, XCL1, CXCL8, C1QC, C1QB, SNAI2, TYROBP, COL1A2, SNAP25, NTS, CXCL2, AGT) suggested hub-DEGs guided 10 candidate drug-molecules treatment OC. Hence, our procedure might be an effective computational tool exploring potential profiles diagnosis any disease.

Language: Английский

Citations

2
Discovery of Bacterial Key Genes from 16S rRNA-Seq Profiles That Are Associated with the Complications of SARS-CoV-2 Infections and Provide Therapeutic Indications DOI Creative Commons
Md. Kaderi Kibria, Md. Ahad Ali, Muhammad Yaseen

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(4), P. 432 - 432

Published: March 28, 2024

SARS-CoV-2 infections, commonly referred to as COVID-19, remain a critical risk both human life and global economies. Particularly, COVID-19 patients with weak immunity may suffer from different complications due the bacterial co-infections/super-infections/secondary infections. Therefore, variants of alternative antibacterial therapeutic agents are required inhibit those infection-causing drug-resistant pathogenic bacteria. This study attempted explore these pathogens their inhibitors by using integrated statistical bioinformatics approaches. By analyzing 16S rRNA sequence profiles, at first, we detected five genera taxa (Bacteroides, Parabacteroides, Prevotella Clostridium, Atopobium, Peptostreptococcus) based on differentially abundant bacteria between infection control samples that significantly enriched in 23 metabolic pathways. A total 183 genes were found Then, top-ranked 10 (accB, ftsB, glyQ, hldD, lpxC, lptD, mlaA, ppsA, ppc, tamB) selected key (bKGs) protein–protein interaction (PPI) network analysis. bKG-guided eight drug molecules (Bemcentinib, Ledipasvir, Velpatasvir, Tirilazad, Acetyldigitoxin, Entreatinib, Digitoxin, Elbasvir) molecular docking. Finally, binding stability three Velpatasvir) against receptors (hldD, lptD) was investigated computing free energies dynamic (MD) simulation-based MM-PBSA techniques, respectively, be stable. findings this could useful resources for developing proper treatment plan co-/super-/secondary-infection

Language: Английский

Citations

2
Exploring bacterial key genes and therapeutic agents for breast cancer among the Ghanaian female population: Insights from In Silico analyses DOI Creative Commons
Md. Kaderi Kibria, Md. Ahad Ali, Md. Nurul Haque Mollah

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(11), P. e0312493 - e0312493

Published: Nov. 25, 2024

Breast cancer (BC) is yet a significant global health challenge across various populations including Ghana, though several studies on host-genome associated with BC have been investigated molecular mechanisms of development and progression, candidate therapeutic agents. However, little attention has given microbial genome in this regard, although alterations microbiota epigenetic modifications are recognized as substantial risk factors for BC. This study focused identifying bacterial key genes (bKGs) infections the Ghanaian population exploring potential drug molecules by targeting these bKGs through silico analyses. At first, 16S rRNA sequence data were downloaded from NCBI database comprising 520 samples patients 442 healthy controls. Analysis rRNA-Seq showed differences abundance between groups identified 26 differential genera threshold values at |log2FC|>2.0 p-value≤0.05. It was observed that two Prevotella Anaerovibria significantly upregulated others downregulated. Functional analysis based all 19 MetaCyc signaling pathways, twelve which enriched containing 165 Top-ranked 10 mdh, pykF, gapA, zwf, pgi, tpiA, pgk, pfkA, ppsA, pykA BC-causing protein-protein interaction network analysis. Subsequently, bKG-guided top ranked Digitoxin, Digoxin, Ledipasvir, Suramin, Ergotamine, Venetoclax, Nilotinib, Conivaptan, Dihydroergotamine, Elbasvir using docking The stability top-ranked three drug-target complexes (Digitoxin-pykA, Digoxin-mdh, Ledipasvir-pgi) confirmed dynamics simulation studies. Therefore, findings might be useful resources to wet-lab researchers further experimental validation therapies against

Language: Английский

Citations

1
In-silico discovery of common molecular signatures for which SARS-CoV-2 infections and lung diseases stimulate each other, and drug repurposing DOI Creative Commons
Muhammad Habibulla Alamin, Md. Matiur Rahaman,

Farzana Ferdousi

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(7), P. e0304425 - e0304425

Published: July 18, 2024

COVID-19 caused by SARS-CoV-2 is a global health issue. It yet severe risk factor to the patients, who are also suffering from one or more chronic diseases including different lung diseases. In this study, we explored common molecular signatures for which infections and stimulate each other, associated candidate drug molecules. We identified both (Asthma, Tuberculosis, Cystic Fibrosis, Pneumonia, Emphysema, Bronchitis, IPF, ILD, COPD ) causing top-ranked 11 shared genes ( STAT1 , TLR4 CXCL10 CCL2 JUN DDX58 IRF7 ICAM1 MX2 IRF9 ISG15 as hub of differentially expressed (hub-sDEGs). The gene ontology (GO) pathway enrichment analyses hub-sDEGs revealed some crucial pathogenetic processes regulatory network analysis detected 6 TFs proteins micro RNAs key transcriptional post-transcriptional factors hub-sDEGs, respectively. Then proposed guided three repurposable molecules (Entrectinib, Imatinib, Nilotinib), treatment against with This recommendation based on results obtained docking using AutoDock Vina GLIDE module Schrödinger. selected were optimized through density functional theory (DFT) observing their good chemical stability. Finally, binding stability highest-ranked receptor protein RELA top-ordered drugs Nilotinib) 100 ns dynamic (MD) simulations YASARA Desmond Schrödinger observed consistent performance. Therefore, findings study might be useful resources diagnosis therapies patients

Language: Английский

Citations

1
The association of Sirtuin1 (SIRT1) polymorphism and downregulation of STAT4 gene expression with increased susceptibility to COVID-19 infection DOI Open Access
Nora Mostafa,

May Elsherbiny Badr,

Olfat Shaker

et al.

Egyptian Journal of Basic and Applied Sciences, Journal Year: 2023, Volume and Issue: 10(1), P. 711 - 721

Published: Sept. 11, 2023

Sirtuin1 (SIRT1) is an epigenetic modulator that belongs to sirtuins family and participates in many physiologic reactions, as genomic stabilization, apoptosis, proliferation, inflammation. STAT4 (signal transducer activator of transcription 4) gene a component JAK-STAT signaling pathway, which plays key role activating cellular-mediated immune responses. The present study aimed investigate the association between SIRT1 rs12778366 SNP, expression level susceptibility COVID-19 infections well their correlation clinicopathological data.The included 100 ICU patients with severe infection age- sex-matched healthy controls. DNA was extracted. Genotyping SNP (rs12778366) performed, Total RNA extracted from PBMCs. Reverse done. levels were evaluated GAPDH internal control using real-time PCR. We found significantly higher frequency ‘C’ allele C/T genotype case vs. control. low strength (φ = 0.105 for alleles, 0.154 genotypes). This associated (P < 0.001) increased tendency lower respiratory complications. Median (FC) (Median 0.18, 95% CI 0.15–0.27) than normal value 1.0. difference statistically significant (Hodges-Lehmann location estimator 0.217, P 0.001). polymorphism decreased are correlate its phenotypic manifestations.

Language: Английский

Citations

1
Altered DNA methylation pattern contributes to differential epigenetic immune signaling in the upper respiratory airway of COVID-19 patients DOI
Melissa Govender, Jyotirmoy Das, Francis R. Hopkins

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 30, 2024

Abstract The emergence of SARS-CoV-2 has had a profound adverse impact on global health and continues to remain threat worldwide. disease spectrum COVID-19 ranges from asymptomatic fatal clinical outcomes especially in the elderly population individuals with underlying medical conditions. host immune responses cells at protein DNA levels remains largely ambiguous. In case-control study, here we explored methylation patterns upper respiratory airway determine how infection altered status requiring hospitalization for COVID-19. We performed arrays nasopharyngeal swabs inclusion/hospitalization as well 6 weeks post-inclusion. Our study reveals distinct pattern patients compared healthy controls, characterized by 317 779 differentially methylated CpGs. Notably, within transcription start sites gene body, exhibited higher number genes/CpGs elevated levels. Enrichment analysis genes highlighted associated inflammatory functions. Some -induced CpG methylations were transient, returning normal Enriched interest included IL-17A, pivotal cytokine implicated inflammation healing, NUP93, antiviral innate immunity. Further, six our data set, OAS1, CXCR5, APP, CCL20, CNR2, C3AR1, found enrichment previous studies. Additionally, RNAse1 RNAse2 emerged key regulators, while IL-18 played role various biological processes patients. Overall, results demonstrates that major modifying many this could have implications conditioning airways individual response future infections.

Language: Английский

Citations

0