Cardiovascular health interacts with cognitive and mental health in complex ways, yet little is known about the phenotypic and genetic links of heart-brain systems. We quantified heart-brain connections using multiorgan magnetic resonance imaging (MRI) data from more than 40,000 subjects. Heart MRI traits displayed numerous association patterns with brain gray matter morphometry, white matter microstructure, and functional networks. We identified 80 associated genomic loci ( P < 6.09 × 10 −10 ) for heart MRI traits, which shared genetic influences with cardiovascular and brain diseases. Genetic correlations were observed between heart MRI traits and brain-related traits and disorders. Mendelian randomization suggests that heart conditions may causally contribute to brain disorders. Our results advance a multiorgan perspective on human health by revealing heart-brain connections and shared genetic influences.
As an anatomical extension of the brain, the retina of the eye is synaptically connected to the visual cortex, establishing physiological connections between the eye and the brain. Despite the unique opportunity retinal structures offer for assessing brain disorders, less is known about their relationship to brain structure and function. Here we present a systematic cross-organ genetic architecture analysis of eye-brain connections using retina and brain imaging endophenotypes. Novel phenotypic and genetic links were identified between retinal imaging biomarkers and brain structure and function measures derived from multimodal magnetic resonance imaging (MRI), many of which were involved in the visual pathways, including the primary visual cortex. In 65 genomic regions, retinal imaging biomarkers shared genetic influences with brain diseases and complex traits, 18 showing more genetic overlaps with brain MRI traits. Mendelian randomization suggests that retinal structures have bidirectional genetic causal links with neurological and neuropsychiatric disorders, such as Alzheimer's disease. Overall, cross-organ imaging genetics reveals a genetic basis for eye-brain connections, suggesting that the retinal images can elucidate genetic risk factors for brain disorders and disease-related changes in intracranial structure and function.
Muilti-modality data are ubiquitous in biology, especially that we have entered the multi-omics era, when we can measure the same biological object (cell) from different aspects (omics) to provide a more comprehensive insight into the cellular system. When dealing with such multi-omics data, the first step is to determine the correspondence among different modalities. In other words, we should match data from different spaces corresponding to the same object. This problem is particularly challenging in the single-cell multi-omics scenario because such data are very sparse with extremely high dimensions. Secondly, matched single-cell multi-omics data are rare and hard to collect. Furthermore, due to the limitations of the experimental environment, the data are usually highly noisy. To promote the single-cell multi-omics research, we overcome the above challenges, proposing a novel framework to align and integrate single-cell RNA-seq data and single-cell ATAC-seq data. Our approach can efficiently map the above data with high sparsity and noise from different spaces to a low-dimensional manifold in a unified space, making the downstream alignment and integration straightforward. Compared with the other state-of-the-art methods, our method performs better in both simulated and real single-cell data. The proposed method is helpful for the single-cell multi-omics research. The improvement for integration on the simulated data is significant.
Motivation We have entered the multi-omics era and can measure cells from different aspects. Hence, we can get a more comprehensive view by integrating or matching data from different spaces corresponding to the same object. However, it is particularly challenging in the single-cell multi-omics scenario because such data are very sparse with extremely high dimensions. Though some techniques can be used to measure scATAC-seq and scRNA-seq simultaneously, the data are usually highly noisy due to the limitations of the experimental environment. Results To promote single-cell multi-omics research, we overcome the above challenges, proposing a novel framework, contrastive cycle adversarial autoencoders, which can align and integrate single-cell RNA-seq data and single-cell ATAC-seq data. Con-AAE can efficiently map the above data with high sparsity and noise from different spaces to a coordinated subspace, where alignment and integration tasks can be easier. We demonstrate its advantages on several datasets. Availability Zenodo link: https://zenodo.org/badge/latestdoi/368779433 github: https://github.com/kakarotcq/Con-AAE. Supplementary information Supplementary data are available at Bioinformatics online.
Motivation Recently, machine learning models have achieved tremendous success in prioritizing candidate genes for genetic diseases. These models are able to accurately quantify the similarity among disease and genes based on the intuition that similar genes are more likely to be associated with similar diseases. However, the genetic features these methods rely on are often hard to collect due to high experimental cost and various other technical limitations. Existing solutions of this problem significantly increase the risk of overfitting and decrease the generalizability of the models. Results In this work, we propose a graph neural network (GNN) version of the Learning under Privileged Information paradigm to predict new disease gene associations. Unlike previous gene prioritization approaches, our model does not require the genetic features to be the same at training and test stages. If a genetic feature is hard to measure and therefore missing at the test stage, our model could still efficiently incorporate its information during the training process. To implement this, we develop a Heteroscedastic Gaussian Dropout algorithm, where the dropout probability of the GNN model is determined by another GNN model with a mirrored GNN architecture. To evaluate our method, we compared our method with four state-of-the-art methods on the Online Mendelian Inheritance in Man dataset to prioritize candidate disease genes. Extensive evaluations show that our model could improve the prediction accuracy when all the features are available compared to other methods. More importantly, our model could make very accurate predictions when >90% of the features are missing at the test stage. Availability and implementation Our method is realized with Python 3.7 and Pytorch 1.5.0 and method and data are freely available at: https://github.com/juanshu30/Disease-Gene-Prioritization-with-Privileged-Information-and-Heteroscedastic-Dropout.
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