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Highly perturbed ge...
Highly perturbed genes and hub genes associated with type 2 diabetes in different tissues of adult humans : a bioinformatics analytic workflow
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- De Silva, Kushan (författare)
- Monash University,Monash Univ, Fac Med Nursing & Hlth Sci, Monash Ctr Hlth Res & Implementat, Sch Publ Hlth & Prevent Med, Clayton, Vic 3168, Australia.
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- Demmer, Ryan T (författare)
- University of Minnesota,Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.;Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
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- Jönsson, Daniel (författare)
- Malmö universitet,Malmö University,Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups,Odontologiska fakulteten (OD),Lund Univ, Dept Clin Sci, S-21428 Malmo, Sweden
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- Mousa, Aya (författare)
- Monash University,Monash Univ, Fac Med Nursing & Hlth Sci, Monash Ctr Hlth Res & Implementat, Sch Publ Hlth & Prevent Med, Clayton, Vic 3168, Australia.
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- Forbes, Andrew (författare)
- Monash University,Monash Univ, Fac Med Nursing & Hlth Sci, Sch Publ Hlth & Prevent Med, Biostat Unit,Div Res Methodol, Melbourne, Vic 3004, Australia.
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- Enticott, Joanne (författare)
- Monash University,Monash Univ, Fac Med Nursing & Hlth Sci, Monash Ctr Hlth Res & Implementat, Sch Publ Hlth & Prevent Med, Clayton, Vic 3168, Australia.
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Monash University Monash Univ, Fac Med Nursing & Hlth Sci, Monash Ctr Hlth Res & Implementat, Sch Publ Hlth & Prevent Med, Clayton, Vic 3168, Australia (creator_code:org_t)
- 2022-07-05
- 2022
- Engelska.
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Ingår i: Functional & Integrative Genomics. - : Springer Science and Business Media LLC. - 1438-793X .- 1438-7948. ; 22:5, s. 1003-1029
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Type 2 diabetes (T2D) has a complex etiology which is not yet fully elucidated. The identification of gene perturbations and hub genes of T2D may deepen our understanding of its genetic basis. We aimed to identify highly perturbed genes and hub genes associated with T2D via an extensive bioinformatics analytic workflow consisting of five steps: systematic review of Gene Expression Omnibus and associated literature; identification and classification of differentially expressed genes (DEGs); identification of highly perturbed genes via meta-analysis; identification of hub genes via network analysis; and downstream analysis of highly perturbed genes and hub genes. Three meta-analytic strategies, random effects model, vote-counting approach, and p value combining approach, were applied. Hub genes were defined as those nodes having above-average betweenness, closeness, and degree in the network. Downstream analyses included gene ontologies, Kyoto Encyclopedia of Genes and Genomes pathways, metabolomics, COVID-19-related gene sets, and Genotype-Tissue Expression profiles. Analysis of 27 eligible microarrays identified 6284 DEGs (4592 downregulated and 1692 upregulated) in four tissue types. Tissue-specific gene expression was significantly greater than tissue non-specific (shared) gene expression. Analyses revealed 79 highly perturbed genes and 28 hub genes. Downstream analyses identified enrichments of shared genes with certain other diabetes phenotypes; insulin synthesis and action-related pathways and metabolomics; mechanistic associations with apoptosis and immunity-related pathways; COVID-19-related gene sets; and cell types demonstrating over- and under-expression of marker genes of T2D. Our approach provided valuable insights on T2D pathogenesis and pathophysiological manifestations. Broader utility of this pipeline beyond T2D is envisaged.
Ämnesord
- NATURVETENSKAP -- Biologi -- Genetik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology (hsv//eng)
Nyckelord
- COVID-19
- Computational Biology
- Diabetes Mellitus, Type 2/genetics
- Humans
- Insulin
- Meta-Analysis as Topic
- Systematic Reviews as Topic
- Workflow
- Differential gene expression
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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