NExON-Bayes: A Bayesian approach to network estimation informed by ordinal covariates

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Main Authors: Feest, Joseph, Ruffieux, Hélène, Lingjærde, Camilla, Xi, Xiaoyue
Format: Preprint
Published: 2025
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author Feest, Joseph
Ruffieux, Hélène
Lingjærde, Camilla
Xi, Xiaoyue
author_facet Feest, Joseph
Ruffieux, Hélène
Lingjærde, Camilla
Xi, Xiaoyue
contents In heterogeneous disease settings, accounting for intrinsic sample variability is crucial for obtaining reliable and interpretable omic network estimates. However, most graphical model analyses of biomedical data assume homogeneous conditional dependence structures, potentially leading to misleading conclusions. To address this, we propose a joint Gaussian graphical model that leverages sample-level ordinal covariates (e.g., disease stage) to account for heterogeneity and improve the estimation of partial correlation structures. Our modelling framework, called NExON-Bayes, extends the graphical spike-and-slab framework to account for ordinal covariates, jointly estimating their relevance to the graph structure and leveraging them to improve the accuracy of network estimation. To scale to high-dimensional omic settings, we develop an efficient variational inference algorithm tailored to our model. Through simulations, we demonstrate that our method outperforms the vanilla graphical spike-and-slab (with no covariate information), as well as other state-of-the-art network approaches which exploit covariate information. Applying our method to reverse phase protein array data from patients diagnosed with stage I, II or III breast carcinoma, we estimate the behaviour of proteomic networks as breast carcinoma progresses. Our model provides insights not only through inspection of the estimated proteomic networks, but also of the estimated ordinal covariate dependencies of key groups of proteins within those networks, offering a comprehensive understanding of how biological pathways shift across disease stages. Availability and Implementation: A user-friendly R package for NExON-Bayes with tutorials is available on Github at github.com/jf687/NExON.
format Preprint
id arxiv_https___arxiv_org_abs_2508_21649
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle NExON-Bayes: A Bayesian approach to network estimation informed by ordinal covariates
Feest, Joseph
Ruffieux, Hélène
Lingjærde, Camilla
Xi, Xiaoyue
Methodology
In heterogeneous disease settings, accounting for intrinsic sample variability is crucial for obtaining reliable and interpretable omic network estimates. However, most graphical model analyses of biomedical data assume homogeneous conditional dependence structures, potentially leading to misleading conclusions. To address this, we propose a joint Gaussian graphical model that leverages sample-level ordinal covariates (e.g., disease stage) to account for heterogeneity and improve the estimation of partial correlation structures. Our modelling framework, called NExON-Bayes, extends the graphical spike-and-slab framework to account for ordinal covariates, jointly estimating their relevance to the graph structure and leveraging them to improve the accuracy of network estimation. To scale to high-dimensional omic settings, we develop an efficient variational inference algorithm tailored to our model. Through simulations, we demonstrate that our method outperforms the vanilla graphical spike-and-slab (with no covariate information), as well as other state-of-the-art network approaches which exploit covariate information. Applying our method to reverse phase protein array data from patients diagnosed with stage I, II or III breast carcinoma, we estimate the behaviour of proteomic networks as breast carcinoma progresses. Our model provides insights not only through inspection of the estimated proteomic networks, but also of the estimated ordinal covariate dependencies of key groups of proteins within those networks, offering a comprehensive understanding of how biological pathways shift across disease stages. Availability and Implementation: A user-friendly R package for NExON-Bayes with tutorials is available on Github at github.com/jf687/NExON.
title NExON-Bayes: A Bayesian approach to network estimation informed by ordinal covariates
topic Methodology
url https://arxiv.org/abs/2508.21649