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
Summary
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.
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.
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