Search bioRxiv⌕ Search

Biology subjects

Oexle, K.

Publications and source records attributed to Oexle, K..

2 recordsLinked to original sources

Can we predict sleep health based on brain features? A large-scale machine learning study

BackgroundsSeveral correlational or group comparison evidence highlighted robust associations between sleep health and macro-scale brain organization. However, inter-individual variability is critical in such interplay. Therefore, in this study, we aimed to investigate the role of brain imaging features in predicting diverse sleep health-related characteristics at the individual subject level using the Machine Learning (ML) approach. MethodsA sample of 28,088 participants from the UK Biobank was employed to calculate 4677 structural and functional neuroimaging markers. Then, we employed them to predict self-reported insomnia symptoms, sleep duration, easiness of getting up in the morning, chronotype, daily nap, daytime sleepiness, and snoring. To assess the predictability of brain features, we built seven different linear and nonlinear ML models for each sleep health-related characteristic. ResultsWe performed extensive ML analyses that involved more than 19 years of compute time. We observed relatively low performance in predicting all sleep health-related characteristics from brain images (e.g., balanced accuracy ranging between 0.50-0.59). Across all models, the best performance achieved was 0.59, using a linear ML model to predict the ease of getting up in the morning. In fact, a similar performance was achieved with models trained solely on age and sex, indicating that these demographic factors might be the ones driving the predictions. ConclusionsThe low capability of multimodal neuroimaging markers in predicting sleep health-related characteristics, even under extensive ML optimization in a large population sample, suggests a complex relationship between sleep health and brain organization.

neuroscience↗

Intronic elements associated with insomnia and restless legs syndrome exhibit cell type-specific epigenetic features contributing to MEIS1 regulation

A highly evolutionarily conserved MEIS1 intronic region is strongly associated with restless legs syndrome (RLS) and insomnia. To understand its regulatory function, we dissected the region by analyzing chromatin accessibility, enhancer-promoter contacts, DNA methylation, and eQTLs in different human neural cell types and tissues. We observed specific activity with respect to cell type and developmental maturation, indicating a prominent role for distinct highly conserved intronic elements in forebrain inhibitory neuron differentiation. Two elements were hypomethylated in neural cells with higher MEIS1 expression, suggesting a role of enhancer demethylation in gene regulation. MEIS1 eQTLs showed a striking modular chromosomal distribution, with forebrain eQTLs clustering in intron 8/9. CRISPR interference targeting of individual elements in this region attenuated MEIS1 expression, revealing a complex regulatory interplay of distinct elements. In summary, we found that MEIS1 regulation is organized in a modular pattern. Disease-associated intronic regulatory elements control MEIS1 expression with cell type and maturation stage specificity, particularly in the inhibitory neuron lineage. The precise spatiotemporal activity of these elements likely contributes to the pathogenesis of insomnia and RLS.

genetics↗