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Filtering the rejection set while preserving false discovery rate control.

Eugene Katsevich1, Chiara Sabatti2, Marina Bogomolov3

  • 1Department of Statistics, University of Pennsylvania.

Journal of the American Statistical Association
|June 22, 2023
PubMed
Summary
This summary is machine-generated.

We introduce Focused BH, a method to adjust multiple testing procedures when hypotheses have structures like ICD or GO. This ensures reliable results even after filtering, maintaining false discovery rate control.

Keywords:
Gene Ontology enrichment analysisdirected acyclic graphouter nodesphenome-wide association studystructured multiple testingtree

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Area of Science:

  • Statistical methodology
  • Bioinformatics
  • Genomics

Background:

  • Hypothesis structures (e.g., ICD, GO) create redundancies in multiple testing.
  • Filtering hypothesis rejections can invalidate statistical guarantees.
  • Interpretability is hindered by redundant rejections.

Purpose of the Study:

  • To propose Focused BH, a principled method for adjusting multiple testing after applying pre-specified filters.
  • To ensure false discovery rate control when using domain-specific hypothesis structures.
  • To provide a flexible methodology applicable to various filtering scenarios.

Main Methods:

  • Developed the Focused BH methodology to incorporate pre-specified filters.
  • Provided theoretical proofs for false discovery rate control under specific conditions.
  • Conducted simulations to evaluate performance across diverse settings.

Main Results:

  • Focused BH maintains false discovery rate control, even with monotonic filters and positively dependent p-values.
  • Simulations demonstrate strong performance of Focused BH in various scenarios.
  • The method proved practical in real-world analyses using ICD and GO data.

Conclusions:

  • Focused BH offers a reliable approach to multiple testing with structured hypotheses and filtering.
  • This methodology enhances the interpretability of results without compromising statistical validity.
  • Focused BH is applicable to diverse scientific domains with structured data.