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      Molecular crosstalk between COVID-19 and Alzheimer’s disease using microarray and RNA-seq datasets: A system biology approach

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          Abstract

          Objective

          Coronavirus disease 2019 (COVID-19) is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The clinical and epidemiological analysis reported the association between SARS-CoV-2 and neurological diseases. Among neurological diseases, Alzheimer’s disease (AD) has developed as a crucial comorbidity of SARS-CoV-2. This study aimed to understand the common transcriptional signatures between SARS-CoV-2 and AD.

          Materials and methods

          System biology approaches were used to compare the datasets of AD and COVID-19 to identify the genetic association. For this, we have integrated three human whole transcriptomic datasets for COVID-19 and five microarray datasets for AD. We have identified differentially expressed genes for all the datasets and constructed a protein–protein interaction (PPI) network. Hub genes were identified from the PPI network, and hub genes-associated regulatory molecules (transcription factors and miRNAs) were identified for further validation.

          Results

          A total of 9,500 differentially expressed genes (DEGs) were identified for AD and 7,000 DEGs for COVID-19. Gene ontology analysis resulted in 37 molecular functions, 79 cellular components, and 129 biological processes were found to be commonly enriched in AD and COVID-19. We identified 26 hub genes which includes AKT1, ALB, BDNF, CD4, CDH1, DLG4, EGF, EGFR, FN1, GAPDH, INS, ITGB1, ACTB, SRC, TP53, CDC42, RUNX2, HSPA8, PSMD2, GFAP, VAMP2, MAPK8, CAV1, GNB1, RBX1 , and ITGA2B. Specific miRNA targets associated with Alzheimer’s disease and COVID-19 were identified through miRNA target prediction. In addition, we found hub genes-transcription factor and hub genes-drugs interaction. We also performed pathway analysis for the hub genes and found that several cell signaling pathways are enriched, such as PI3K-AKT, Neurotrophin, Rap1, Ras, and JAK–STAT.

          Conclusion

          Our results suggest that the identified hub genes could be diagnostic biomarkers and potential therapeutic drug targets for COVID-19 patients with AD comorbidity.

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          Most cited references89

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

            In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0550-8) contains supplementary material, which is available to authorized users.
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              clusterProfiler: an R package for comparing biological themes among gene clusters.

              Increasing quantitative data generated from transcriptomics and proteomics require integrative strategies for analysis. Here, we present an R package, clusterProfiler that automates the process of biological-term classification and the enrichment analysis of gene clusters. The analysis module and visualization module were combined into a reusable workflow. Currently, clusterProfiler supports three species, including humans, mice, and yeast. Methods provided in this package can be easily extended to other species and ontologies. The clusterProfiler package is released under Artistic-2.0 License within Bioconductor project. The source code and vignette are freely available at http://bioconductor.org/packages/release/bioc/html/clusterProfiler.html.
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                Author and article information

                Contributors
                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                07 June 2023
                2023
                07 June 2023
                : 10
                : 1151046
                Affiliations
                Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology , Vellore, Tamil Nadu, India
                Author notes

                Edited by: Thirumal Kumar, D. Meenakshi Academy of Higher Education and Research, India

                Reviewed by: Prabhash Kumar Jha, Brigham and Women's Hospital, Harvard Medical School, United States; Konda Mani Saravanan, Bharath Institute of Higher Education and Research, India

                *Correspondence: S. Sajitha Lulu, ssajithalulu@ 123456vit.ac.in

                ORCID: S. Sajitha Lulu https://orcid.org/0000-0002-3392-4168

                This article was submitted to Precision Medicine, a section of the journal Frontiers in Medicine

                Article
                10.3389/fmed.2023.1151046
                10286240
                dc391708-4b21-4fe2-a0ac-405034b202ef
                Copyright © 2023 Premkumar and Sajitha Lulu.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 January 2023
                : 20 March 2023
                Page count
                Figures: 10, Tables: 5, Equations: 2, References: 90, Pages: 16, Words: 9050
                Categories
                Medicine
                Original Research

                covid-19,alzheimer’s disease,regulatory networks,comorbidity,biomarkers

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