arXiv subjects

Alessia Mapelli

Publications and source records attributed to Alessia Mapelli.

3 recordsLinked to original sources

arXiv2026

Enhancing comorbidity network inference with risk-enriched health trajectories embedding

Multimorbidity poses a growing challenge for individual health, reducing quality of life and increasing treatment burden, resulting in a multiplicative impact on healthcare system management and fragmented care trajectories. Comorbidity networks could provide crucial insight into characterising multimorbidity and disease relationships. However, existing approaches to comorbidity network construction face critical limitations: they overlook temporal information by relying on cross-sectional statistics, produce biased association estimates by ignoring confounding due to shared risk factors, and fail to distinguish between direct and indirect disease associations, thereby yielding fully connected networks. To address these limitations, we develop a methodological framework for population-level disease network inference that uses individual health trajectories to learn disease associations, capturing semantic similarity and temporal co-occurrence. Sparse network estimation is achieved via Gaussian Graphical Models with Lasso regularisation, informed by prior clinical knowledge on shared risk factors derived from a dedicated confounding evaluation step. Applied to UK Biobank data comprising 24 cardiometabolic diseases and 76 risk factors, the resulting network revealed clinically meaningful disease patterns. Topological analysis identifies key pathological hubs, reveals potential actionable targets for multimorbidity management, and identifies four distinct disease communities that align with the established cardiometabolic taxonomy. Building on this community structure, we derive community-based patient representations that capture disease progression dynamics. Clustering these representations reveals four progression phenotypes with significantly different long-term survival trajectories, highlighting the potential of the framework for risk stratification and personalised care.

stat.AP↗

arXiv2026

Prior-informed conditional Gaussian graphical models: an application to protein interaction network reconstruction

Protein-protein interaction (PPI) networks, estimated from high-throughput omics data, foster biomarker discovery and precision medicine. Gaussian graphical models (GGMs) offer a principled reconstruction framework. Yet, existing applications face two limitations: they overlook the rich existing knowledge encoded in curated biological databases, and they assume a homogeneous network structure across all individuals, neglecting the influence of covariates or confounding factors on these interactions and preventing personalised representations. Even though these limitations have been addressed separately in previous work, no current approach resolves them simultaneously. We introduce a prior-informed conditional Gaussian graphical model that integrates database-derived interaction priors with covariate-dependent network modeling in a unified, scalable framework. The key methodological innovation is a structured, weighted penalty that selectively incorporates priors into population-level network estimation, while leaving context-specific perturbations entirely data-driven, as curated databases capture canonical interactions rather than disease-specific signals. Simulation studies demonstrate consistent and robust improvements in population-level network reconstruction across diverse settings, even when prior knowledge is imperfect. Applied to UK Biobank cardiometabolic proteomics (n = 49,129, p = 366 proteins), the method recovers T2D-associated network perturbations, identifying 34 network-central candidate biomarkers, several detectable only through their connectivity, not differential expression, and revealing six biologically coherent protein communities with distinct pathway enrichments spanning metabolic, cardiovascular, and cancer-related processes. Code is available at https://github.com/AlessiaMapelli/Prior-informed-conditional-GGMs.

stat.AP↗

arXiv2026

A neighbour selection approach for identifying differential networks in conditional functional graphical models

Estimating how different brain regions communicate with each other using EEG data is valuable both for medical research and clinical diagnosis. This involves quantifying the statistical dependencies among the activities of different brain areas, captured by the time-varying electric field recorded by scalp sensors. These dependencies can vary within and across individuals also in relationship with external factors such as age, mental state, or disease severity. Motivated by this problem, we propose a novel neighbor selection approach based on Gaussian functional graphical models and functional-on-functional regression to identify which brain regions interact and how interaction strength changes with individual features or covariates (e.g., age or clinical status). Our approach is fully automated and data-driven, and, in principle, can handle any number of continuous and categorical covariates simultaneously. Unlike existing approaches, it also produces results that are easy to interpret: one can directly assess whether the strength of each estimated interaction increases or decreases as the value of a given covariate varies. We evaluate our method through extensive simulation experiments and an application to real EEG data. The results demonstrate clear advantages over existing approaches, including more accurate estimation of brain connections and reduced computational cost, especially in high-dimensional settings involving a large number of brain regions and large sample sizes.

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