A genetically based computational drug repurposing framework for rapid identification of candidate compounds: application to COVID-19.

Background: The development and approval of novel drugs are typically time-intensive and expensive. Leveraging a computational drug repurposing framework that integrates disease-relevant genetically regulated gene expression (GReX) and large longitudinal electronic medical record (EMR) databases can expedite the repositioning of existing medications. However, validating computational predictions of the drug repurposing framework remains a challenge.

Chromatin accessibility provides a window into the genetic etiology of human brain disease.

Neuropsychiatric and neurodegenerative diseases have a significant genetic component. Risk variants often affect the noncoding genome, altering cis-regulatory elements (CREs) and chromatin structure, ultimately impacting gene expression. Chromatin accessibility profiling methods, especially assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), have been used to pinpoint disease-associated SNPs and link them to affected genes and cell types in the brain.

Enhancing single-cell transcriptomics using interposed anchor oligonucleotide sequences.

Single-cell transcriptomics, which utilises barcodes and unique molecular identifiers (UMIs) for polyA+ mRNA capture, is compromised by oligonucleotide synthesis errors. To address this, we modified the oligonucleotide capture design and integrated an interposed anchor between the barcode and the UMI. This design significantly reduces the need to discard reads due to synthesis inaccuracies.

Associations between rural hospital closures and acute and post-acute care access and outcomes.

Objective: To determine whether rural hospital closures affected hospital and post-acute care (PAC) use and outcomes.

Study Setting And Design: Using a staggered difference-in-differences design, we evaluated associations between 32 rural hospital closures and changes in county-level: (1) travel distances to and lengths of stay at hospitals; (2) functional limitations at and time from hospital discharge to start of PAC episode; (3) 30-day readmissions and mortality and hospitalizations for a fall-related injury; and (4) population-level hospitalization and death rates.

Data Sources And Analytic Sample: 100% Medicare claims and home health and skilled nursing facility clinical data to identify approximately 3 million discharges for older fee-for-service Medicare beneficiaries.

Single-Nucleus Atlas of Cell-Type Specific Genetic Regulation in the Human Brain.

Genetic risk variants for common diseases are predominantly located in non-coding regulatory regions and modulate gene expression. Although bulk tissue studies have elucidated shared mechanisms of regulatory and disease-associated genetics, the cellular specificity of these mechanisms remains largely unexplored. This study presents a comprehensive single-nucleus multi-ancestry atlas of genetic regulation of gene expression in the human prefrontal cortex, comprising 5.