Higher-Order Biomarkers Through Network Motif Mining: A COVID-19 Case Study

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 2, 2025

Abstract We introduce a novel approach for analyzing expression data by integrating patient-level profiles with Protein-Protein interaction network from the STRING database. Our pipeline leverages motif mining to identify recurring sets (motifs) of interacting biomolecules characterized specific patterns, providing deeper insights into underlying biological processes. applied our method publicly available dataset plasma protein measurements patients mild/moderate COVID-19 and compared features those found conventional differential analysis. Motif demonstrated better performance in classification models hierarchical clustering. Of note, they were able resolve interpatient variability during clustering, while traditional failed do so. Interestingly, these discriminatory performances achieved using smaller largely different set proteins. is highly flexible capacity integrate multiple modes presents an exciting line analysis biomarker discovery as well general biology.

Язык: Английский

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Methylation patterns of the nasal epigenome of hospitalized SARS-CoV-2 positive patients reveal insights into molecular mechanisms of COVID-19

BMC Medical Genomics, Год журнала: 2025, Номер 18(1)

Опубликована: Апрель 1, 2025

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has varied presentations from asymptomatic to death. Efforts identify factors responsible for differential COVID-19 severity include but are not limited genome wide association studies (GWAS) and transcriptomic analysis. More recently, variability in host epigenomic profiles have garnered attention, providing links severity. However, whole epigenome analysis of the tract, target tissue SARS-CoV-2, remains ill-defined. We interrogated nasal methylome pathophysiologic drivers through bisulfite sequencing (WGBS) samples positive individuals with mild presentation disease. noted DNA methylation intergenic regions low methylated (LMRs), demonstrating importance distal regulatory elements gene regulation illness. Additionally, we demonstrated pathways implicated immune cell recruitment function, inflammatory response. found significant hypermethylation FUT4 promoter implicating impaired neutrophil adhesion also identified ELF5 binding sites suggesting downregulation targets cavity as a factor phenotypic variability. This study marker response SARS-CoV-2 infection, enhancer-like playing roles. It is difficult discern whether this predisposing COVID-19, or if differences occur These may contribute severity, conversely, system respond infection

Язык: Английский

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Integrated multi-sample transcriptomic analysis of COVID-19 patients against controls using a bioinformatics pipeline

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Июнь 4, 2025

Prior coronavirus disease 2019 (COVID-19) transcriptomic studies using diverse methods for differential gene expression (DGE) profiling of specific samples yielded inconsistent results. To validate the shared molecular patterns COVID-19 across cell, tissue, and systemic levels, we conducted a systematic rank combination meta-analysis differentially expressed (DEG) profiles sourced from various sample types standardised bioinformatics pipeline consisting DESeq2, RankProd, weighted correlation network analysis (WGCNA). Consistently upregulated ISGs (including key hub IFIT2), compared with interleukins were identified in swab samples, reflecting dominant innate immune responses at viral entry point. Blood revealed functions neurological regulation, highlighting complex interplay regulation. Significant enrichment immunoglobulin-related extracellular matrix genes indicates their role host adaptive immunity long-term tissue samples. Novel GPD1 CYP4A11 related to metabolic dysregulation identified, potentially contributing severity disease. These findings portray basis progression localised effects finally tissue-specific remodelling, providing insights that may inform diagnostic therapeutic development.

Язык: Английский

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Bioinformatics and system biology approach to identify the influences among COVID-19, influenza, and HIV on the regulation of gene expression

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Март 27, 2024

Background Coronavirus disease (COVID-19), caused by SARS-CoV-2, has emerged as a infectious disease, coexisting with widespread seasonal and sporadic influenza epidemics globally. Individuals living HIV, characterized compromised immune systems, face an elevated risk of severe outcomes increased mortality when affected COVID-19. Despite this connection, the molecular intricacies linking COVID-19, influenza, HIV remain unclear. Our research endeavors to elucidate shared pathways markers in individuals concurrently infected COVID-19 influenza. Furthermore, we aim identify potential medications that may prove beneficial managing these three interconnected illnesses. Methods Sequencing data for (GSE157103), (GSE185576), (GSE195434) were retrieved from GEO database. Commonly expressed differentially genes (DEGs) identified across datasets, followed infiltration analysis diagnostic ROC on DEGs. Functional enrichment was performed using GO/KEGG Gene Set Enrichment Analysis (GSEA). Hub screened through Protein-Protein Interaction networks (PPIs) among miRNAs, transcription factors, drug chemicals, diseases, RNA-binding proteins conducted based hub genes. Finally, quantitative PCR (qPCR) expression verification undertaken selected Results The datasets revealed total 22 DEGs, majority exhibiting area under curve value exceeding 0.7. GSEA primarily highlighted signaling associated ribosomes tumors. ten included IFI44L , IFI44 RSAD2 ISG15 IFIT3 OAS1 EIF2AK2 IFI27 OASL EPSTI1 . Additionally, five crucial miRNAs (hsa-miR-8060, hsa-miR-6890-5p, hsa-miR-5003-3p, hsa-miR-6893-3p, hsa-miR-6069), essential factors (CREB1, CEBPB, EGR1, EP300, IRF1), top significant chemicals (estradiol, progesterone, tretinoin, calcitriol, fluorouracil, methotrexate, lipopolysaccharide, valproic acid, silicon dioxide, cyclosporine) identified. Conclusion This provides valuable insights into targets, pathways, biomarkers facing complex intersection HIV. These findings hold promise enhancing precision diagnosis treatment co-infected

Язык: Английский

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Thymosin α1 modulated the immune landscape of COVID-19 patients revealed by single-cell RNA and TCR sequencing

International Immunopharmacology, Год журнала: 2023, Номер 124, С. 110983 - 110983

Опубликована: Сен. 26, 2023

Язык: Английский

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Endogenous retroviruses activate MARCO-mediated inflammatory response to block retroviral infection

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 5, 2024

Abstract Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections and can profoundly affect the host antiviral innate immune response, although mechanisms by which these changes occur largely unknown. Here we report that chicken-specific ERVs exert genetic resistance to exogenous retrovirus infection. Mechanistically, activated scavenger receptor MARCO (macrophage with collagenous structure)-mediated TLR3-IL-1β inflammatory response in macrophages. Under presence MARCO, macrophages viral infection through inducing response. Conversely, lack increased replication levels attenuated MARCO-mediated ligand delivery enhances IL-1β expression is responsible for inhibition. Restoring or overcomes Our study provides new insights into molecular underlying defense against may have important implications development novel therapeutic strategies

Язык: Английский

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Virus–Host Protein Interaction Network of the Hepatitis E Virus ORF2-4 by Mammalian Two-Hybrid Assays

Viruses, Год журнала: 2023, Номер 15(12), С. 2412 - 2412

Опубликована: Дек. 12, 2023

Throughout their life cycle, viruses interact with cellular host factors, thereby influencing propagation, range, cell tropism and pathogenesis. The hepatitis E virus (HEV) is an underestimated RNA in which knowledge of the virus–host interaction network to date limited. Here, two related high-throughput mammalian two-hybrid approaches (MAPPIT KISS) were used screen for HEV-interacting proteins. Promising hits examined on protein function, involved pathway(s), relation other viruses. We identified 37 ORF2 hits, 187 ORF3 91 ORF4. Several had functions cycle distinct focused SHARPIN RNF5 as candidate ORF3, they are RLR-MAVS pathway interferon (IFN) induction during viral infections. Knocking out (KO) resulted a different IFN response upon transfection, compared wild-type cells. Moreover, infection was increased KO cells decreased In conclusion, MAPPIT KISS valuable tools study interactions, providing insights into poorly understood HEV cycle. further provide evidence new factors

Язык: Английский

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