Clonal Decomposition and DNA Replication States Defined by Scaled Single-Cell Genome Sequencing.

Accurate measurement of clonal genotypes, mutational processes, and replication states from individual tumor-cell genomes will facilitate improved understanding of tumor evolution. We have developed DLP+, a scalable single-cell whole-genome sequencing platform implemented using commodity instruments, image-based object recognition, and open source computational methods. Using DLP+, we have generated a resource of 51,926 single-cell genomes and matched cell images from diverse cell types including cell lines, xenografts, and diagnostic samples with limited material.

Dissociation of solid tumor tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses.

Background: Single-cell RNA sequencing (scRNA-seq) is a powerful tool for studying complex biological systems, such as tumor heterogeneity and tissue microenvironments. However, the sources of technical and biological variation in primary solid tumor tissues and patient-derived mouse xenografts for scRNA-seq are not well understood.

Results: We use low temperature (6 °C) protease and collagenase (37 °C) to identify the transcriptional signatures associated with tissue dissociation across a diverse scRNA-seq dataset comprising 155,165 cells from patient cancer tissues, patient-derived breast cancer xenografts, and cancer cell lines.

Probabilistic cell-type assignment of single-cell RNA-seq for tumor microenvironment profiling.

Single-cell RNA sequencing has enabled the decomposition of complex tissues into functionally distinct cell types. Often, investigators wish to assign cells to cell types through unsupervised clustering followed by manual annotation or via 'mapping' to existing data. However, manual interpretation scales poorly to large datasets, mapping approaches require purified or pre-annotated data and both are prone to batch effects.

Active management of atrial fibrillation or flutter in emergency department patients with renal impairment is associated with a higher risk of adverse events and treatment failure.

Objective: Atrial fibrillation or flutter (AFF) patients with renal impairment have poor long-term prognosis, but their emergency department (ED) management has not been described. We investigated the association of renal impairment upon outcomes after rate or rhythm control (RRC) including ED-based adverse events (AE) and treatment failure.

Methods: This cohort study used an electrocardiogram database from two urban centres to identify consecutive AFF patients and reviewed charts to obtain comorbidities, ED management, including RRC, prespecified AE, and treatment failure.