Integration of estimated regional gene expression with neuroimaging and clinical phenotypes at biobank scale.

An understanding of human brain individuality requires the integration of data on brain organization across people and brain regions, molecular and systems scales, as well as healthy and clinical states. Here, we help advance this understanding by leveraging methods from computational genomics to integrate large-scale genomic, transcriptomic, neuroimaging, and electronic-health record data sets. We estimated genetically regulated gene expression (gr-expression) of 18,647 genes, across 10 cortical and subcortical regions of 45,549 people from the UK Biobank. First, we showed that patterns of estimated gr-expression reflect known genetic-ancestry relationships, regional identities, as well as inter-regional correlation structure of directly assayed gene expression. Second, we performed transcriptome-wide association studies (TWAS) to discover 1,065 associations between individual variation in gr-expression and gray-matter volumes across people and brain regions. We benchmarked these associations against results from genome-wide association studies (GWAS) of the same sample and found hundreds of novel associations relative to these GWAS. Third, we integrated our results with clinical associations of gr-expression from the Vanderbilt Biobank. This integration allowed us to link genes, via gr-expression, to neuroimaging and clinical phenotypes. Fourth, we identified associations of polygenic gr-expression with structural and functional MRI phenotypes in the Human Connectome Project (HCP), a small neuroimaging-genomic data set with high-quality functional imaging data. Finally, we showed that estimates of gr-expression and magnitudes of TWAS were generally replicable and that the p-values of TWAS were replicable in large samples. Collectively, our results provide a powerful new resource for integrating gr-expression with population genetics of brain organization and disease.

Unsupervised ECG Analysis: A Review.

Electrocardiography is the gold standard technique for detecting abnormal heart conditions. Automatic detection of electrocardiogram (ECG) abnormalities helps clinicians analyze the large amount of data produced daily by cardiac monitors. As thenumber of abnormal ECG samples with cardiologist-supplied labels required to train supervised machine learning models is limited, there is a growing need for unsupervised learning methods for ECG analysis. Unsupervised learning aims to partition ECG samples into distinct abnormality classes without cardiologist-supplied labels-a process referred to as ECG clustering. In addition to abnormality detection, ECG clustering has recently discovered inter and intra-individual patterns that reveal valuable information about the whole body and mind, such as emotions, mental disorders, and metabolic levels. ECG clustering can also resolve specific challenges facing supervised learning systems, such as the imbalanced data problem, and can enhance biometric systems. While several reviews exist on supervised ECG systems, a comprehensive review of unsupervised ECG analysis techniques is still lacking. This study reviews ECG clustering techniques developed mainly in the last decade. The focus will be on recent machine learning and deep learning algorithms and their practical applications. We critically review and compare these techniques, discuss their applications and limitations, and provide future research directions. This review provides further insights into ECG clustering and presents the necessary information required to adopt the appropriate algorithm for a specific application.