arXiv subjects

Hélène Ruffieux

Publications and source records attributed to Hélène Ruffieux.

8 recordsLinked to original sources

arXiv2026

Modeling Time-course Gene Expression Data through Bayesian Partition Functional Principal Component Analysis

High-dimensional biomarkers such as gene expression levels are now routinely measured over time, allowing biological processes to be studied dynamically rather than through cross-sectional snapshots. However, existing methods do not adequately address the central applied challenges posed by such data: simultaneously reducing dimensionality, quantifying inter-individual variability and uncovering temporal structure shared across biomarkers. We introduce Partition Functional Principal Component Analysis (PFPCA), a Bayesian model that jointly learns shared temporal patterns and clusters variables according to their latent dynamics. PFPCA combines a mixture model with multivariate functional principal component analysis performed within each group. We develop a scalable mean-field variational algorithm for joint inference of functional principal component loadings, individual-level scores, group assignments and partition sizes. Simulations show clear gains from joint inference: PFPCA recovers both the partition and the latent functional structure more accurately than a two-step baseline. In the most challenging settings, PFPCA retrieves the true partition in 27% of replicates compared with 1% for the two-step baseline. Applied to longitudinal gene-expression data from individuals experimentally infected with H3N2 influenza virus, PFPCA identifies groups of genes with coordinated activation patterns and reveals temporal signatures associated with immune-response dynamics and symptom status.

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arXiv2026

A scalable Bayesian functional factor model for high-dimensional longitudinal molecular data

Large-scale longitudinal molecular profiling is now firmly established in biomedical research, prompted by the need to uncover coordinated biomarker trajectories reflecting the dynamics of underlying biological mechanisms and characterise patient heterogeneity in disease progression. While a range of statistical tools exist for either longitudinal modelling or high-dimensional analysis, there is no unified framework tailored to address these questions jointly. Motivated by a longitudinal COVID-19 study conducted in Cambridge hospitals, we propose a Bayesian functional factor model to address this gap. The framework combines latent factor modelling with functional principal component analysis to represent shared temporal programmes across subsets of variables while capturing individual variation through low-dimensional functional scores. We specify sparsity-inducing priors that yield interpretable factor structure and allow the effective number of factors to be inferred via overspecification. An annealed variational algorithm ensures efficient joint posterior inference at scale. The approach achieves accurate recovery of temporal structure in simulations with up to 20 000 variables. Application to the COVID-19 data reveals clinically meaningful heterogeneity in recovery dynamics through interpretable subject-level scores capturing coordinated inflammatory and immune-response pathway activity. The methodology is implemented in the R package bayesSYNC.

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arXiv2026

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

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.

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arXiv2024

Efficient Bayesian functional principal component analysis of irregularly-observed multivariate curves

The analysis of multivariate functional curves has the potential to yield important scientific discoveries in domains such as healthcare, medicine, economics and social sciences. However, it is common for real-world settings to present longitudinal data that are both irregularly and sparsely observed, which introduces important challenges for the current functional data methodology. A Bayesian hierarchical framework for multivariate functional principal component analysis is proposed, which accommodates the intricacies of such irregular observation settings by flexibly pooling information across subjects and correlated curves. The model represents common latent dynamics via shared functional principal component scores, thereby effectively borrowing strength across curves while circumventing the computationally challenging task of estimating covariance matrices. These scores also provide a parsimonious representation of the major modes of joint variation of the curves and constitute interpretable scalar summaries that can be employed in follow-up analyses. Estimation is carried out using variational inference, which combines efficiency, modularity and approximate posterior density estimation, enabling the joint analysis of large datasets with parameter uncertainty quantification. Detailed simulations assess the effectiveness of the approach in sharing information from sparse and irregularly sampled multivariate curves. The methodology is also exploited to estimate the molecular disease courses of individual patients with SARS-CoV-2 infection and characterise patient heterogeneity in recovery outcomes; this study reveals key coordinated dynamics across the immune, inflammatory and metabolic systems, which are associated with survival and long-COVID symptoms up to one year post disease onset. The approach is implemented in the R package bayesFPCA.

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arXiv2024

A modelling framework for detecting and leveraging node-level information in Bayesian network inference

Bayesian graphical models are powerful tools to infer complex relationships in high dimension, yet are often fraught with computational and statistical challenges. If exploited in a principled way, the increasing information collected alongside the data of primary interest constitutes an opportunity to mitigate these difficulties by guiding the detection of dependence structures. For instance, gene network inference may be informed by the use of publicly available summary statistics on the regulation of genes by genetic variants. Here we present a novel Gaussian graphical modelling framework to identify and leverage information on the centrality of nodes in conditional independence graphs. Specifically, we consider a fully joint hierarchical model to simultaneously infer (i) sparse precision matrices and (ii) the relevance of node-level information for uncovering the sought-after network structure. We encode such information as candidate auxiliary variables using a spike-and-slab submodel on the propensity of nodes to be hubs, which allows hypothesis-free selection and interpretation of a sparse subset of relevant variables. As efficient exploration of large posterior spaces is needed for real-world applications, we develop a variational expectation conditional maximisation algorithm that scales inference to hundreds of samples, nodes and auxiliary variables. We illustrate and exploit the advantages of our approach in simulations and in a gene network study which identifies hub genes involved in biological pathways relevant to immune-mediated diseases.

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arXiv2023

Scalable Multiple Network Inference with the Joint Graphical Horseshoe

Network models are useful tools for modelling complex associations. If a Gaussian graphical model is assumed, conditional independence is determined by the non-zero entries of the inverse covariance (precision) matrix of the data. The Bayesian graphical horseshoe estimator provides a robust and flexible framework for precision matrix inference, as it introduces local, edge-specific parameters which prevent over-shrinkage of non-zero off-diagonal elements. However, for many applications such as statistical omics, the current implementation based on Gibbs sampling becomes computationally inefficient or even unfeasible in high dimensions. Moreover, the graphical horseshoe has only been formulated for a single network, whereas interest has grown in the network analysis of multiple data sets that might share common structures. We propose (i) a scalable expectation conditional maximisation (ECM) algorithm for obtaining the posterior mode of the precision matrix in the graphical horseshoe, and (ii) a novel joint graphical horseshoe estimator, which borrows information across multiple related networks to improve estimation. We show, on both simulated and real omics data, that our single-network ECM approach is more scalable than the existing graphical horseshoe Gibbs implementation, while achieving the same level of accuracy. We also show that our joint-network proposal successfully leverages shared edge-specific information between networks while still retaining differences, outperforming state-of-the-art methods at any level of network similarity.

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arXiv2020

A global-local approach for detecting hotspots in multiple-response regression

We tackle modelling and inference for variable selection in regression problems with many predictors and many responses. We focus on detecting hotspots, i.e., predictors associated with several responses. Such a task is critical in statistical genetics, as hotspot genetic variants shape the architecture of the genome by controlling the expression of many genes and may initiate decisive functional mechanisms underlying disease endpoints. Existing hierarchical regression approaches designed to model hotspots suffer from two limitations: their discrimination of hotspots is sensitive to the choice of top-level scale parameters for the propensity of predictors to be hotspots, and they do not scale to large predictor and response vectors, e.g., of dimensions $10^3-10^5$ in genetic applications. We address these shortcomings by introducing a flexible hierarchical regression framework that is tailored to the detection of hotspots and scalable to the above dimensions. Our proposal implements a fully Bayesian model for hotspots based on the horseshoe shrinkage prior. Its global-local formulation shrinks noise globally and hence accommodates the highly sparse nature of genetic analyses, while being robust to individual signals, thus leaving the effects of hotspots unshrunk. Inference is carried out using a fast variational algorithm coupled with a novel simulated annealing procedure that allows efficient exploration of multimodal distributions.

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arXiv2017

Efficient inference for genetic association studies with multiple outcomes

Combined inference for heterogeneous high-dimensional data is critical in modern biology, where clinical and various kinds of molecular data may be available from a single study. Classical genetic association studies regress a single clinical outcome on many genetic variants one by one, but there is an increasing demand for joint analysis of many molecular outcomes and genetic variants in order to unravel functional interactions. Unfortunately, most existing approaches to joint modelling are either too simplistic to be powerful or are impracticable for computational reasons. Inspired by Richardson et al. (2010, Bayesian Statistics 9), we consider a sparse multivariate regression model that allows simultaneous selection of predictors and associated responses. As Markov chain Monte Carlo (MCMC) inference on such models can be prohibitively slow when the number of genetic variants exceeds a few thousand, we propose a variational inference approach which produces posterior information very close to that of MCMC inference, at a much reduced computational cost. Extensive numerical experiments show that our approach outperforms popular variable selection methods and tailored Bayesian procedures, dealing within hours with problems involving hundreds of thousands of genetic variants and tens to hundreds of clinical or molecular outcomes.

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