QClus: a droplet filtering algorithm for enhanced snRNA-seq data quality in challenging samples.

Single-nuclei RNA sequencing remains a challenge for many human tissues, as incomplete removal of background signal masks cell-type-specific signals and interferes with downstream analyses. Here, we present Quality Clustering (QClus), a droplet filtering algorithm targeted toward challenging samples. QClus uses additional metrics, such as cell-type-specific marker gene expression, to cluster nuclei and filter empty and highly contaminated droplets, providing reliable filtering of samples with varying number of nuclei and contamination levels.

Transcriptomic and spatial dissection of human ex vivo right atrial tissue reveals proinflammatory microvascular changes in ischemic heart disease.

Cardiovascular disease plays a central role in the electrical and structural remodeling of the right atrium, predisposing to arrhythmias, heart failure, and sudden death. Here, we dissect with single-nuclei RNA sequencing (snRNA-seq) and spatial transcriptomics the gene expression changes in the human ex vivo right atrial tissue and pericardial fluid in ischemic heart disease, myocardial infarction, and ischemic and non-ischemic heart failure using asymptomatic patients with valvular disease who undergo preventive surgery as the control group. We reveal substantial differences in disease-associated gene expression in all cell types, collectively suggesting inflammatory microvascular dysfunction and changes in the right atrial tissue composition as the valvular and vascular diseases progress into heart failure.