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Abstract Microbial networks offer critical insights into community structure, ecological interactions and host–microbe dynamics. However, constructing reliable microbiome networks remains challenging due to variability among existing inference methods, limited overlap between inferred networks and the absence of a gold standard (a universally accepted reference for benchmarking) for validation.We developedCMiNet, an R package and interactive Shiny App(https://cminet.wid.wisc.edu) that enables consensus microbiome network construction by integrating up to 10 widely used inference algorithms.CMiNetsupports both correlation‐based and conditional dependence‐based methods and provides users with flexible options to construct individual or consensus networks across different approaches.CMiNetintegrates results from multiple inference methods through a voting strategy that retains edges supported by a user‐defined number of methods. To assess robustness, we complement this with a bootstrap analysis that quantifies edge stability under resampling. By jointly reporting method support and bootstrap confidence,CMiNetprovides a reproducible framework that explicitly communicates both agreement across methods and stability under perturbation.We appliedCMiNetto gut and soil microbiome datasets, constructing consensus networks that retained edges supported by multiple methods and confirmed by bootstrap reproducibility values. To identify disease‐associated taxa, we developed an integrative strategy that compared results across machine learning, differential abundance and network‐based approaches, ensuring that selected taxa were consistently recovered across methods. In the soil dataset, this analysis highlighted key taxa such asKtedonobacteria, Acidobacteriae, Vicinamibacteria, MB‐A2‐108, IgnavibacteriaandAnaerolineae, all of which were confirmed by multiple independent strategies.
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This content will become publicly available on January 1, 2027
A hybrid framework for disease biomarker discovery in microbiome research combining Bayesian networks, machine learning, and network-based methods
Abstract Microbiome research faces two central challenges, namely constructing reliable networks, where nodes represent microbial taxa and edges represent their associations, and identifying significant disease-associated taxa. To address the first challenge, we developed CMIMN, a novel R package that applies a Bayesian network framework based on conditional mutual information to infer microbial interaction networks. To further enhance reliability, we construct a consensus microbiome network by integrating results from CMIMN and three widely used methods, including Sparse Inverse Covariance Estimation for Ecological Association Inference (SPIEC-EASI), Semi-Parametric Rank-based correlation and partial correlation Estimation (SPRING), and Sparse Correlations for Compositional Data (SPARCC). This consensus approach, which overlays and weights edges shared across methods, reduces inconsistencies and provides a more biologically meaningful view of microbial relationships. To address the second challenge, we designed a multi-method feature selection framework that combines machine learning with network-based strategies. Our machine learning pipeline applies distinct algorithms and identifies key taxa based on their consistent importance across models. Complementing this, we employ two network-based strategies that prioritize taxa based on centrality differences between networks constructed from healthy samples and disease-affected samples, as well as a composite scoring system that ranks nodes using integrated network metrics. We applied CMIMN on soil microbiome data from potato fields affected by common scab disease. Bootstrap analysis confirmed the robustness of CMIMN, and the consensus network further improved stability and interpretability. The multi-method framework enhances confidence in identifying soil microbial taxa associated with potato disease. Notably, we identified Bacteroidota, WPS-2, and Proteobacteria at the Phylum level; Actinobacteria, AD3, Bacilli, Anaerolineae, and Ktedonobacteria at the Class level; and C0119, Defluviicoccales, Bacteroidales, and Ktedonobacterales at the Order level as key taxa associated with disease status.
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- Award ID(s):
- 2144367
- PAR ID:
- 10678431
- Publisher / Repository:
- Biology Methods and Protocols
- Date Published:
- Journal Name:
- Biology Methods and Protocols
- Volume:
- 11
- Issue:
- 1
- ISSN:
- 2396-8923
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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