bioRxiv Science⌕ Search

Biology subjects

Huels, A.

Publications and source records attributed to Huels, A..

5 recordsLinked to original sources

Adversarial random forests for omics synthesis

Data availability is critical for understanding complex disease pathways and developing robust predictive models. Although high-throughput omics technologies have improved insight into disease mechanisms, data acquisition from inaccessible tissues such as the central nervous system remains a major limitation, causing small sample sizes and complicating early prediction of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Generative modeling has emerged as a powerful approach for synthesizing data to support downstream clustering and prediction with small sample size, but existing methods rarely handle high-dimensional tabular omics data effectively. Adversarial random forests (ARFs) provide a well-performing framework for tabular data generation but are not designed for high-dimensional settings. To address this limitation, we introduce high-dimensional ARF (h-ARF), an extension of ARF optimized for integrated clinical and high-dimensional omics data. Using benchmarks across nine datasets and eight performance metrics, we show that h-ARF better preserves both feature distributions, and downstream clustering and prediction utilities compared with ARFs. The method is implemented in the open-source R package harf, available on CRAN.

bioinformatics↗

Epigenetic and brain age across development: Performance and associations in the MIND consortium

Understanding how biological age measures perform across development lays the groundwork for investigations into lifespan trajectories of healthy aging. We provide the most comprehensive assessment of epigenetic and brain age models across development (birth to 24 years; [≤]20,917 observations across 15 cohorts), evaluating how these models associate with chronological age and with each other, and how these associations change across development. Chronological age-prediction accuracy of epigenetic and brain age models was modest and varied substantially. Accuracy improved with age and stabilized by middle childhood. Few brain and fewer epigenetic clocks performed stably and well across all developmental stages. Performance was better when age range and tissue corresponded between training and testing data. Associations between epigenetic-brain age residuals were small, and changed little across development, tissues or clock generation. Given this developmentally dynamic system of epigenetic-brain age performances and associations, we give key recommendations to improve developmental research in this field.

neuroscience↗

A healthy childhood environment helps to combat inherited susceptibility to obesity

ObjectivesTo investigate the degree by which the inherited susceptibility to obesity is modified by environmental factors during childhood and adolescence. DesignCohort study with repeated measurements of diet, lifestyle factors and anthropometry. SettingThe pan-European IDEFICS/I.Family cohort Participants8,609 repeated observations from 3,098 children aged 2 to 16 years, examined between 2007 and 2014. Main outcome measuresBody mass index (BMI) and waist circumference. Genome-wide polygenic risk scores (PRS) to capture the inherited susceptibility of obesity were calculated using summary statistics from independent genome-wide association studies of BMI. Gene-environment interactions of the PRS with sociodemographic (European region, socioeconomic status) and lifestyle factors (diet, screen time, physical activity) were estimated. ResultsThe PRS was strongly associated with BMI (r2 = 0.11, p-value = 7.9 x 10-81) and waist circumference (r2 = 0.09, p-value = 1.8 x 10-71) in our cohort. The associations with BMI increased from r2=0.03 in 3-year olds to r2=0.18 in 14-year olds and associations with waist circumference from r2=0.03 to r2=0.14. Being in the top decile of the PRS distribution was associated with 3.63 times higher odds for obesity (95% confidence interval (CI): [2.57, 5.14]). We observed significant interactions with demographic and lifestyle factors for BMI as well as waist circumference. The risk of becoming obese among those with higher genetic susceptibility was ~38% higher in children from Southern Europe (BMI: p-interaction = 0.0066, Central vs. Southern Europe) and ~61% higher in children with a low parental education (BMI: p-interaction = 0.0012, low vs. high). Furthermore, the risk was attenuated by a higher intake of dietary fiber (BMI: p-interaction=0.0082) and shorter screen times (BMI: p-interaction=0.018). ConclusionsOur results highlight that a healthy childhood environment might partly offset a genetic predisposition to obesity during childhood and adolescence.

genetics↗

Brain DNA Methylation Patterns in CLDN5 Associated With Cognitive Decline

ObjectiveCognitive decline is a hallmark of dementia; however, the brain epigenetic signature of cognitive decline is unclear. We investigated the associations between brain tissue-based DNA methylation and cognitive trajectory. MethodsWe performed a brain epigenome-wide association study of cognitive trajectory in 636 participants from the Religious Order Study and the Rush Memory and Aging Project (ROS/MAP) using DNA methylation profiles of the dorsal lateral prefrontal cortex (dPFC). To maximize our power to detect epigenetic associations, we used the recently developed Gene Association with Multiple Traits (GAMuT) test to analyze the five measured cognitive domains simultaneously. ResultsWe found an epigenome-wide association for differential methylation of sites in the Claudin-5 (CLDN5) locus and cognitive trajectory (p-value x 9.96 x 10-7), which was robust to adjustment for cell type proportions (p-value = 8.52 x 10-7). This association was primarily driven by association with declines in episodic (p-value = 4.65 x 10-6) and working memory (p-value = 2.54 x 10-7). This association between methylation in CLDN5 and cognitive decline was independent of beta-amyloid and neurofibrillary tangle pathology and present in participants with low levels of neuropathology. In addition, only 13-31% of the association between methylation and cognitive decline was mediated through levels of neuropathology, whereas the major part of the association was independent of it. InterpretationWe identified methylation in CLDN5 as new epigenetic factor associated with cognitive trajectory. Higher levels of methylation in CLDN5 were associated with faster cognitive decline implicating the blood brain barrier in maintenance of cognitive trajectory.

genetics↗

Benefits of improved air quality on aging lungs. Impacts of genetics and obesity

IntroductionThe beneficial effect of improving air quality on lung function in the elderly remains unclear. We examined associations between decline in air pollutants and lung function and effect modifications by genetics and BMI in elderly German women.\n\nMethodsData were analysed from the prospective SALIA cohort study (N=601). Spirometry was conducted at baseline (1985-1994; 55 years), in 2007-2010 and in 2012-2013. Air pollution concentrations at home addresses were determined for each time point using land-use regression models. GLI z-scores were calculated. Weighted genetic risk scores (GRS) were determined from lung function-related risk alleles and used to investigate interactions with improved air quality. Adjusted linear mixed models were fitted.\n\nResultsAir pollution levels decreased substantially during the study period. Reduction of air pollution was associated with an increase of z-scores for FEV1 and FEV1/FVC. For a decrease of 10 g/m3 in NO2, the z-score for FEV1 increased by 0.14 (95%CI: 0.01; 0.26). However, with an increasing number of lung function-related risk alleles, the benefit from improved air quality decreased (GRSxNO2-interaction:p=0.029). Interactions with BMI were not significant.\n\nConclusionsReduction of air pollution is associated with a relative improvement of lung function in elderly women, but also depends on their genetic make-up.

epidemiology↗