Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

Nature Communications
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. nature communications
  3. articles
  4. article
Local graph estimation with pathwise false discovery control
Download PDF
Download PDF
  • Article
  • Open access
  • Published: 12 May 2026

Local graph estimation with pathwise false discovery control

  • Omar Melikechi  ORCID: orcid.org/0000-0003-1052-73001,
  • David B. Dunson1,
  • Noureddine Melikechi2 &
  • …
  • Jeffrey W. Miller3 

Nature Communications (2026) Cite this article

  • 2514 Accesses

  • 2 Altmetric

  • Metrics details

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Cancer epidemiology
  • Cancer genomics
  • Machine learning
  • Probabilistic data networks
  • Statistical methods

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.

Similar content being viewed by others

High-plex imaging of RNA and proteins at subcellular resolution in fixed tissue by spatial molecular imaging

Article 06 October 2022

Mapping human tissues with highly multiplexed RNA in situ hybridization

Article Open access 20 March 2024

Epigenetically conferred ring-stage survival in Plasmodium falciparum against artemisinin treatment

Article Open access 28 August 2025

Acknowledgements

D.B.D. and O.M. were supported in part by funding from Merck & Co. and the National Institutes of Health (NIH) grant R01ES035625. D.B.D. was supported in part by the Office of Naval Research grant N000142412626. J.W.M. and O.M. were supported in part by the Collaborative Center for X-linked Dystonia Parkinsonism (CCXDP). J.W.M. was supported in part by NIH grant R01CA240299. N.M. declares no relevant funding.

Author information

Authors and Affiliations

  1. Department of Statistical Science, Duke University, Durham, NC, USA

    Omar Melikechi & David B. Dunson

  2. Kennedy College of Sciences, University of Massachusetts Lowell, Lowell, MA, USA

    Noureddine Melikechi

  3. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Jeffrey W. Miller

Authors
  1. Omar Melikechi
    View author publications

    Search author on:PubMed Google Scholar

  2. David B. Dunson
    View author publications

    Search author on:PubMed Google Scholar

  3. Noureddine Melikechi
    View author publications

    Search author on:PubMed Google Scholar

  4. Jeffrey W. Miller
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Omar Melikechi.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary information (download PDF )

Transparent Peer Review file (download PDF )

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Melikechi, O., Dunson, D.B., Melikechi, N. et al. Local graph estimation with pathwise false discovery control. Nat Commun (2026). https://doi.org/10.1038/s41467-026-72796-9

Download citation

  • Received: 22 August 2025

  • Accepted: 24 April 2026

  • Published: 12 May 2026

  • DOI: https://doi.org/10.1038/s41467-026-72796-9

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Download PDF

Advertisement

Explore content

  • Research articles
  • Reviews & Analysis
  • News & Comment
  • Videos
  • Collections
  • Subjects
  • Follow us on Facebook
  • Follow us on X
  • Sign up for alerts
  • RSS feed

About the journal

  • Aims & Scope
  • Editors
  • Journal Information
  • Open Access Fees and Funding
  • Calls for Papers
  • Editorial Values Statement
  • Journal Metrics
  • Editors' Highlights
  • Contact
  • Editorial policies
  • Top Articles

Publish with us

  • For authors
  • For Reviewers
  • Language editing services
  • Open access funding
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

Nature Communications (Nat Commun)

ISSN 2041-1723 (online)

nature.com footer links

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2026 Springer Nature Limited

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer