Evidence map›Paper›PMID 40249811›Full record

ArticleScience advances2025

Engineering bacteriophages through deep mining of metagenomic motifs.

Phil Huss, Kristopher Kieft, Anthony Meger, Kyle Nishikawa, Karthik Anantharaman, Srivatsan Raman

Abstract read
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Phage-Based Approaches to ChronicAntibiotics (Basel, Switzerland) · 2026
    Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Pathogen-Phage Geomapping to Overcome Resistance.bioRxiv : the preprint server for biology · 2025
    Article
  12. Article
  13. Optimizing phage therapy with artificial intelligence: a perspective.Frontiers in cellular and infection microbiology · 2025
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Phil HussDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.ORCID 0000-0003-4064-9333
Kristopher KieftDepartment of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.
Anthony MegerDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.ORCID 0000-0003-4463-8471
Kyle NishikawaDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.ORCID 0000-0002-9257-0531
Karthik AnantharamanDepartment of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.ORCID 0000-0002-9584-2491
Srivatsan RamanDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.ORCID 0000-0003-2461-1589

Funding

COMPUTATIONAL FRAMEWORKS FOR PHAGE DISCOVERY, ECOLOGY, AND DYNAMICS FROM METAGENOMESR35GM143024 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI ANANTHARAMAN, KARTHIK · 2021 to 2025
$1.9M
Understanding molecular rules governing bacteriophage specificity and virulence by high-throughput mutational and metagenomic scanningR21AI156785 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI RAMAN, SRIVATSAN · 2021 to 2022
$427k
NIAID NIH HHS R21 AI156785NIGMS NIH HHS R35 GM143024
6 · The paper itself

Abstract

Bacteriophages can adapt to new hosts by altering sequence motifs through recombination or convergent evolution. Where these motifs exist and what fitness advantage they confer remains largely unknown. We report a new method, Metagenomic Sequence Informed Functional Scoring (Meta-SIFT), to find sequence motifs in metagenomic datasets to engineer phage activity. Meta-SIFT uses experimental deep mutational scanning data to create sequence profiles to mine metagenomes for functional motifs invisible to other searches. We experimentally tested ~17,000 Meta-SIFT-derived sequence motifs in the receptor binding protein of the T7 phage. The screen revealed thousands of T7 variants with novel host specificity with motifs sourced from distant families. Position, substitution, and location preferences dictated specificity across a panel of 20 hosts and conditions. To demonstrate therapeutic utility, we engineered active T7 variants against foodborne pathogen

Indexed as

BacteriophagesBacteriophage T7Genetic EngineeringMetagenomeMetagenomics

Identifiers

PMID40249811
PMCPMC12007582

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

None linked

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.