期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 75, 期 4, 页码 1417-1435出版社
IOS PRESS
DOI: 10.3233/JAD-200207
关键词
Alzheimer's disease; Cytoscape network analysis; Gene Ontology; microglia; neuroinflammation; PANTHER
资金
- Alzheimer's Research United Kingdom [ARUK-NAS2017A-1, ARUK-NSG2018-003]
- National Institute for Health Research University College London Hospitals Biomedical Research Centre
- National Human Genome Research Institute [U41 HG002273]
- National Eye Institute of the National Institutes of Health
- National Human Genome Research Institute of the National Institutes of Health
- National Heart, Lung, and Blood Institute of the National Institutes of Health
- National Institute on Aging of the National Institutes of Health
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health
- National Institute of General Medical Sciences of the National Institutes of Health
- National Institute of Mental Health of the National Institutes of Health
- British Heart Foundation
- MRC [MR/L023784/1, MR/L023784/2] Funding Source: UKRI
Background: Gene Ontology (GO) is a major bioinformatic resource used for analysis of large biomedical datasets, for example from genome-wide association studies, applied universally across biological fields, including Alzheimer's disease (AD) research. Objective: We aim to demonstrate the applicability of GO for interpretation of AD datasets to improve the understanding of the underlying molecular disease mechanisms, including the involvement of inflammatory pathways and dysregulated microRNAs (miRs). Methods: We have undertaken a systematic full article GO annotation approach focused on microglial proteins implicated in AD and the miRs regulating their expression. PANTHER was used for enrichment analysis of previously published AD data. Cytoscape was used for visualizing and analyzing miR-target interactions captured from published experimental evidence. Results: We contributed 3,084 new annotations for 494 entities, i.e., on average six new annotations per entity. This included a total of 1,352 annotations for 40 prioritized microglial proteins implicated in AD and 66 miRs regulating their expression, yielding an average of twelve annotations per prioritized entity. The updated GO resource was then used to re-analyze previously published data. The re-analysis showed novel processes associated with AD-related genes, not identified in the original study, such as 'gliogenesis', 'regulation of neuron projection development', or 'response to cytokine', demonstrating enhanced applicability of GO for neuroscience research. Conclusions: This study highlights ongoing development of the neurobiological aspects of GO and demonstrates the value of biocuration activities in the area, thus helping to delineate the molecular bases of AD to aid the development of diagnostic tools and treatments.
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