Evidence map›Paper›PMID 39827261›Full record

ArticleNature communications2025

Incomplete human reference genomes can drive false sex biases and expose patient-identifying information in metagenomic data.

Caitlin Guccione, Lucas Patel, Yoshihiko Tomofuji, Daniel McDonald, Antonio Gonzalez, Gregory D Sepich-Poore, Kyuto Sonehara, Mohsen Zakeri, Yang Chen, Amanda Hazel Dilmore and 9 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. SCiMS: Sex Calling in Metagenomic Sequences.bioRxiv : the preprint server for biology · 2026
    Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. The multi-kingdom cancer microbiome.Nature microbiology · 2025
    Review
  14. Article
  15. Targeted decontamination of sequencing data with CLEAN.NAR genomics and bioinformatics · 2025
    Article
  16. Review
  17. Environmental and Maternal Imprints on Infant Gut Metabolic Programming.bioRxiv : the preprint server for biology · 2025
    Article
  18. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Caitlin Guccione *Division of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Lucas Patel *Bioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA, USA.
Yoshihiko TomofujiDepartment of Genome Informatics, Graduate School of Medicine, the University of Tokyo, Tokyo, 113-8654, Japan.
Daniel McDonaldDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Antonio GonzalezDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Gregory D Sepich-PooreShu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-3443-3715
Kyuto SoneharaDepartment of Genome Informatics, Graduate School of Medicine, the University of Tokyo, Tokyo, 113-8654, Japan.ORCID http://orcid.org/0000-0002-4536-1761
Mohsen ZakeriDepartment of Computer Science, Johns Hopkins University, Baltimore, MD, USA.
Yang ChenDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Amanda Hazel DilmoreDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Neil DamleHalıcıoğlu Data Science Institute, University of California San Diego, La Jolla, CA, USA.
Sergio E BaranziniWeill Institute for Neurosciences. Department of Neurology. University of California, San Francisco (UCSF), San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-0067-194X
George HightowerDepartment of Dermatology, University of California San Diego, La Jolla, CA, USA.
Teruaki NakatsujiDepartment of Dermatology, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-6187-2991
Richard L GalloDepartment of Dermatology, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-1401-7861
Ben LangmeadDepartment of Computer Science, Johns Hopkins University, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-2437-1976
Yukinori OkadaDepartment of Genome Informatics, Graduate School of Medicine, the University of Tokyo, Tokyo, 113-8654, Japan.ORCID http://orcid.org/0000-0002-0311-8472
Kit CurtiusDivision of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla, CA, USA. kcurtius@health.ucsd.edu.ORCID http://orcid.org/0000-0002-2678-0960
Rob KnightDepartment of Pediatrics, University of California San Diego, La Jolla, CA, USA. robknight@ucsd.edu.

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jesse Nodora · 1985 to 2026
$124.9M
Project 4 - Mechanistic studies on the role of the gut microbiome in models for Alzheimer's diseaseU19AG063744 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI ROB KNIGHT, Rima F Kaddurah-Daouk · 2019 to 2026
$54.1M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007198 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHI, NEIL C, INSEL, PAUL A · 1985 to 2024
$29.3M
San Diego Digestive Diseases Research CenterP30DK120515 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Bernd G. Schnabl · 2019 to 2026
$10.8M
Mapping host-microbe-metabolite interactions in 3D to find diet-derived enhancers of immunityDP1AT010885 · NCCIH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KNIGHT, ROB · 2019 to 2023
$5.5M
Bacterial biosensors for the prevention of gastrointestinal cancersR01CA241728 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEFF M HASTY, ROB KNIGHT · 2020 to 2026
$4.2M
Advanced Development of Informatics Technologies for Cancer Research and Management (U24 Clinical Trial Optional)U24CA248454 · NCI · NORTHERN ARIZONA UNIVERSITY · PI CAPORASO, JAMES GREGORY · 2020 to 2024
$3.7M
Multiscale modeling of spatiotemporal evolution in Barrett's esophagusR01CA270235 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Kathleen M. Curtius · 2023 to 2026
$2.3M
Efficient and scalable pangenomes with the move structureR21HG013433 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI LANGMEAD, BENJAMIN THOMAS · 2024 to 2025
$399k
AGA Research Foundation AGA Research Scholar Award AGA2022-13-05NCCIH NIH HHS DP1 AT010885NCI NIH HHS P30 CA023100NCI NIH HHS R01 CA241728NCI NIH HHS R01 CA270235NCI NIH HHS U24 CA248454NHGRI NIH HHS R21 HG013433NIA NIH HHS U19 AG063744NIDDK NIH HHS P30 DK120515NIGMS NIH HHS T32 GM007198U.S. Department of Health & Human Services | Centers for Disease Control and Prevention (CDC) CDC award 75D301-22-C-14717U.S. Department of Health & Human Services | National Institutes of Health (NIH) NIH/NIGMS T32GM007198U.S. Department of Health & Human Services | National Institutes of Health (NIH) NIH Pioneer DP1AT010885U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) NCI U24CA248454
6 · The paper itself

Abstract

As next-generation sequencing technologies produce deeper genome coverages at lower costs, there is a critical need for reliable computational host DNA removal in metagenomic data. We find that insufficient host filtration using prior human genome references can introduce false sex biases and inadvertently permit flow-through of host-specific DNA during bioinformatic analyses, which could be exploited for individual identification. To address these issues, we introduce and benchmark three host filtration methods of varying throughput, with concomitant applications across low biomass samples such as skin and high microbial biomass datasets including fecal samples. We find that these methods are important for obtaining accurate results in low biomass samples (e.g., tissue, skin). Overall, we demonstrate that rigorous host filtration is a key component of privacy-minded analyses of patient microbiomes and provide computationally efficient pipelines for accomplishing this task on large-scale datasets.

Indexed as

Genome, HumanMetagenomicsSexismComputational BiologyFecesFemaleHigh-Throughput Nucleotide SequencingHumansMaleMetagenomeMicrobiota

Identifiers

PMID39827261
PMCPMC11742726

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.