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Using cross-species co-expression to predict metabolic interactions in microbiomes.

Robert A Koetsier1, Zachary L Reitz1, Clara Belzer2

  • 1Bioinformatics Group, Wageningen University, Wageningen, the Netherlands.

Msystems
|December 9, 2025
PubMed
Summary
This summary is machine-generated.

Cross-species gene co-expression analysis predicts microbial interactions and metabolic pathways. This data-driven approach identifies resource competition and specialized functions, guiding microbiome research.

Keywords:
antibioticscoexpressionmetabolic gene clustersynthetic community

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Area of Science:

  • Microbial Ecology
  • Systems Biology
  • Bioinformatics

Background:

  • Metabolic interactions govern microbial community structure and function.
  • Predicting these interactions computationally is crucial but often lacks mechanistic insight.
  • Existing tools often miss underlying metabolic pathways, hindering experimental validation.

Purpose of the Study:

  • To develop and validate a novel approach using cross-species co-expression to predict microbial interactions.
  • To identify specific metabolic pathways involved in competition, cross-feeding, and specialized interactions.
  • To assess the potential for discovering novel gene functions through interaction prediction.

Main Methods:

  • Applied cross-species co-expression analysis to microbial co-culture RNA-sequencing data.
  • Utilized Mucin and Diet-based Minimal Microbiome (MDb-MM) and Hitchhikers of the Rhizosphere (THOR) datasets.
  • Investigated gene and pathway co-expression patterns to infer interaction types.

Main Results:

  • Successfully predicted pathways involved in resource competition within the MDb-MM dataset.
  • Identified links between specialized functions, such as antibiotic and multidrug efflux systems in the THOR dataset.
  • Provided evidence for siderophore co-expression driving interactions in a specific microbial consortium.

Conclusions:

  • Cross-species co-expression is a feasible and data-driven method for predicting microbial interactions and underlying pathways.
  • This approach offers a valuable alternative to complex model-building, reducing bias.
  • The method facilitates the discovery of novel gene functions and informs microbiome engineering.