Local graph estimation with pathwise false discovery control

Many datasets include a small set of variables, such as biomarkers or clinical outcomes, whose relationships to the broader system are of primary scientific interest. Estimating the full network of inter-variable relationships in such settings often obscures local structures around these targets, limiting interpretability. To address this fundamental problem, we introduce local graph estimation, a statistical framework for inferring substructures around target variables. We show that traditional graph estimation methods often fail to recover local structure, and present pathwise feature selection (PFS) as an effective alternative. PFS estimates local subgraphs by iteratively applying feature selection and propagating uncertainty along network paths, providing rigorous finite-sample false discovery control even in settings with mixed variable types and nonlinear dependencies. In four distinct applications spanning environmental and public health, multiomics, brain connectomics, and single-nucleus RNA sequencing, PFS recovers interpretable networks consistent with domain knowledge, highlighting its ability to uncover established mechanisms and generate novel hypotheses.

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Publication Details

Journal
Nature Communications
Published
2026-05-12
DOI
https://doi.org/10.1038/s41467-026-72796-9
Primary Topic
Functional Brain Connectivity Studies
Type
article
Field-Weighted Citation Impact
0.00

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article

Local graph estimation with pathwise false discovery control

Omar Melikechi, Noureddine Melikechi, David B. Dunson, Jeffrey W. Miller
Nature Communications
Functional Brain Connectivity Studies
article

Local graph estimation with pathwise false discovery control

Omar Melikechi, Noureddine Melikechi, David B. Dunson, Jeffrey W. Miller
article en

Abstract

Many datasets include a small set of variables, such as biomarkers or clinical outcomes, whose relationships to the broader system are of primary scientific interest. Estimating the full network of inter-variable relationships in such settings often obscures local structures around these targets, limiting interpretability. To address this fundamental problem, we introduce local graph estimation, a statistical framework for inferring substructures around target variables. We show that traditional graph estimation methods often fail to recover local structure, and present pathwise feature selection (PFS) as an effective alternative. PFS estimates local subgraphs by iteratively applying feature selection and propagating uncertainty along network paths, providing rigorous finite-sample false discovery control even in settings with mixed variable types and nonlinear dependencies. In four distinct applications spanning environmental and public health, multiomics, brain connectomics, and single-nucleus RNA sequencing, PFS recovers interpretable networks consistent with domain knowledge, highlighting its ability to uncover established mechanisms and generate novel hypotheses.

Nature Communications
University of Massachusetts Lowell (US), Harvard University (US), Duke University (US)
Foundation for the National Institutes of Health, National Institutes of Health, Office of Naval Research
Openalex Percentile: Top 5%
Functional Brain Connectivity Studies
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Local graph estimation with pathwise false discovery control — Omar Melikechi, Noureddine Melikechi, et al. · Nature Communications (2026) | TGRS Research Map | TGRS