Journal
BIOSTATISTICS
Volume 23, Issue 3, Pages 860-874Publisher
OXFORD UNIV PRESS
DOI: 10.1093/biostatistics/kxab001
Keywords
Empirical Bayes; Graph-respecting partition; GraphMM; Image analysis; Local false-discovery rate; Mixture model
Funding
- NIH [1U54AI117924, R01 AG040396]
- NSF CAREER [RI 1252725]
- NSF [1740707]
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The Graph-based Mixture Model (GraphMM) is proposed for large-scale testing with graph-associated data to control local false-discovery rates. Compared to procedures that ignore the graph, GraphMM performs better when non-null cases form connected subgraphs. In a study of brain changes associated with Alzheimer's disease onset, GraphMM produces greater yield than conventional large-scale testing procedures.
For large-scale testing with graph-associated data, we present an empirical Bayes mixture technique to score local false-discovery rates (FDRs). Compared to procedures that ignore the graph, the proposed Graph-based Mixture Model (GraphMM) method gains power in settings where non-null cases form connected subgraphs, and it does so by regularizing parameter contrasts between testing units. Simulations show that GraphMM controls the FDR in a variety of settings, though it may lose control with excessive regularization. On magnetic resonance imaging data from a study of brain changes associated with the onset of Alzheimer's disease, GraphMM produces greater yield than conventional large-scale testing procedures.
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