Rahul A. Jonas | Search arXiv

arXiv2026

Prediction bias in biological ageing models

Biological ageing markers have attracted growing interest, with models estimating age from organ imaging or blood biomarkers. An estimated age above chronological age or the age-specific population expectation is assumed to reflect accelerated ageing and poorer health. Previous research has supported this assumption through positive associations between disease and age gaps or acceleration. However, in this study, we identified a widespread health-dependent prediction bias in ageing markers that affects their key interpretation and application. Specifically, we investigated five ageing markers derived from retinal images, brain MRI, chest radiographs, abdominal CT, and blood tests, and evaluated them using association analyses. We observed the well-recognised phenomenon of regression to the mean (RTM) in the four organ-image based markers, whereby estimated ages were shifted towards the mean age of the training cohort. More importantly, we revealed that the strength of RTM varied with health status, with stronger RTM in unhealthy than in healthy individuals. This differential RTM introduced a health-dependent prediction bias that persisted after calibration and systematically altered associations across age subgroups, suggesting that whole cohort associations may not reflect those observed within individual age subgroups. Additionally, we showed that the tested ageing markers, including PhenoAge derived from blood biomarkers, had limited ability to distinguish health status at the individual level. These findings call for careful interpretation of biological ageing markers and their use in clinical studies, and highlight the need for further development and validation before these ageing markers can reliably inform individual health assessments.

q-bio.QM↗

arXiv2026

oculomix: Hierarchical Sampling for Retinal-Based Systemic Disease Prediction

Oculomics - the concept of predicting systemic diseases, such as cardiovascular disease and dementia, through retinal imaging - has advanced rapidly due to the data efficiency of transformer-based foundation models like RETFound. Image-level mixed sample data augmentations, such as CutMix and MixUp, are frequently used for training transformers, yet these techniques perturb patient-specific attributes, such as medical comorbidity and clinical factors, since they only account for images and labels. To address this limitation, we propose a hierarchical sampling strategy, Oculomix, for mixed sample augmentations. Our method is based on two clinical priors. First (exam level), images acquired from the same patient at the same time point share the same attributes. Second (patient level), images acquired from the same patient at different time points have a soft temporal trend, as morbidity generally increases over time. Guided by these priors, our method constrains the mixing space to the patient and exam levels to better preserve patient-specific characteristics and leverages their hierarchical relationships. The proposed method is validated using ViT models on a five-year prediction of major adverse cardiovascular events (MACE) in a large ethnically diverse population (Alzeye). We show that Oculomix consistently outperforms image-level CutMix and MixUp by up to 3% in AUROC, demonstrating the necessity and value of the proposed method in oculomics.

cs.LG↗