Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
Alzheimer's disease biological domain sub-stratification enhances the precision of functional analyses.
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Cary Gregory A, Ganesh Sai Sruthi Amirtha, Heath Laura, Leal Karina, Kampmann Martin, Longo Frank M, Butler Robert R, Levey Allan L, Carter Gregory W, Wiley Jesse
Аннотация
INTRODUCTION: The Target Enablement to Accelerate Therapy Development for AD (TREAT-AD) bioinformatics pipeline employs a rank-and-organize strategy. Disease-associated genes drive enrichment of large AD-linked endophenotypes. However, these biological areas were too large to promote hypothesis development or target identification. Here we delineate subdomains that map to, and enrich, specific biological processes.
METHODS: To refine the biodomains into more focused areas, we built κ networks out of the Gene Ontology terms in the biodomain and employ shared gene annotation between terms to determine edge weights. κ-value filtration enabled us to identify data-driven subdomains, which we employed in an analysis of TREAT-AD harmonized datasets.
RESULTS: The subdomain enrichment highlights core areas of biological impairment within the biodomain space and facilitates a deeper interpretation of large-scale multiomic datasets.
DISCUSSION: The subdomain mapping of AD-risk-associated processes may facilitate an open-source, open-science shareable resource for the comparison of large datasets for the formulation of future hypotheses and identification of therapeutic targets.
METHODS: To refine the biodomains into more focused areas, we built κ networks out of the Gene Ontology terms in the biodomain and employ shared gene annotation between terms to determine edge weights. κ-value filtration enabled us to identify data-driven subdomains, which we employed in an analysis of TREAT-AD harmonized datasets.
RESULTS: The subdomain enrichment highlights core areas of biological impairment within the biodomain space and facilitates a deeper interpretation of large-scale multiomic datasets.
DISCUSSION: The subdomain mapping of AD-risk-associated processes may facilitate an open-source, open-science shareable resource for the comparison of large datasets for the formulation of future hypotheses and identification of therapeutic targets.