Yazar "Quinn, Julian M. W." seçeneğine göre listele

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    Genome-Wide Integrative Analysis Reveals Common Molecular Signatures in Blood and Brain of Alzheimer's Disease
    (Biointerface Research Applied Chemistry, 2021) Rahman, Md Rezanur; Islam, Tania; Shabjam, Md; Rana, Md Humayun Kabir; Holsinger, R. M. Damian; Quinn, Julian M. W.; Gov, Esra
    The currently utilized neuroimaging and cerebrospinal fluid-based detection of Alzheimers disease (AD) suffer several limitations, including sensitivity, specificity, and cost. Therefore, the identification of AD by analyzing blood gene expression may ameliorate the early diagnosis of the AD. We aimed to identify common genes commonly deregulated in blood and brain in AD. Comprehensive analysis of blood and brain gene expression datasets of AD, eQTL, and epigenetics data was analyzed by the integrative bioinformatics approach. The integrative analysis showed nine differentially expressed genes common to blood cells and brain (CNBD1, SUCLG2-AS1, CCDC65, PDE4D, MTMR1, C3, SLC6A15, LINC01806, and FRG1JP). Analysis of SNP and cis-eQTL data showed 18 genes; namely, HSD17B1, GAS5, RPS5, VKORC1, GLE1, WDR1, RPL12, MORN1, RAD52, SDR39U1, NPHP4, MT1E, SORD, LINC00638, MCM3AP-AS1, GSDMD, RPS9, and GNL2 were observed deregulated AD blood and brain tissues. Functional gene set enrichment analysis demonstrated a significant association of these genes in neurodegeneration-associated molecular pathways. Integrative biomolecular networks revealed dysregulation of several hub transcription factors and microRNAs in AD. Moreover, hub genes were observed associated with significant histone modification. This study detected common molecular biomarkers and pathways in blood and brain tissues in AD that may be potential biomarkers and therapeutic targets in AD.
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    Öğe
    Identification of molecular signatures and pathways to identify novel therapeutic targets in Alzheimer's disease: Insights from a systems biomedicine perspective
    (Academic Press Inc Elsevier Science, 2020) Rahman, Md Rezanur; Islam, Tania; Zaman, Toyfiquz; Shahjaman, Md; Karim, Md Rezaul; Huq, Fazlul; Quinn, Julian M. W.
    Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. However, there are no peripheral biomarkers available that can detect AD onset. This study aimed to identify the molecular signatures in AD through an integrative analysis of blood gene expression data. We used two microarray datasets (GSE4226 and GSE4229) comparing peripheral blood transcriptomes of AD patients and controls to identify differentially expressed genes (DEGs). Gene set and protein overrepresentation analysis, protein-protein interaction (PPI), DEGs-Transcription Factors (TFs) interactions, DEGs-microRNAs (miRNAs) interactions, protein-drug interactions, and protein subcellular localizations analyses were performed on DEGs common to the datasets. We identified 25 common DEGs between the two datasets. Integration of genome scale transcriptome datasets with biomolecular networks revealed hub genes (NOL6, ATF3, TUBB, UQCRC1, CASP2, SND1, VCAM1, BTF3, VPS37B), common transcription factors (FOXC1, GATA2, NFIC, PPARG, USF2, YY1) and miRNAs (mir-20a-5p, mir-93-5p, mir-16-5p, let-7b-5p, mir-7085p, mir-24-3p, mir-26b-5p, mir-17-5p, mir-193-3p, mir-186-5p). Evaluation of histone modifications revealed that hub genes possess several histone modification sites associated with AD. Protein-drug interactions revealed 10 compounds that affect the identified AD candidate biomolecules, including anti-neoplastic agents (Vinorelbine, Vincristine, Vinblastine, Epothilone D, Epothilone B, CYT997, and ZEN-012), a dermatological (Podofilox) and an immunosuppressive agent (Colchicine). The subcellular localization of molecular signatures varied, including nuclear, plasma membrane and cytosolic proteins. In the present study, it was identified blood-cell derived molecular signatures that might be useful as candidate peripheral biomarkers in AD. It was also identified potential drugs and epigenetic data associated with these molecules that may be useful in designing therapeutic approaches to ameliorate AD.