RNA abundance is a powerful indicator of the state of individual cells. Single-cell RNA sequencing can reveal RNA abundance with high quantitative accuracy, sensitivity and throughput1. However, this approach captures only a static snapshot at a point in time, posing a challenge for the analysis of time-resolved phenomena such as embryogenesis or tissue regeneration. Here […]
Single-cell transcriptomics is a versatile tool for exploring heterogeneous cell populations, but as with all genomics experiments, batch effects can hamper data integration and interpretation. The success of batch-effect correction is often evaluated by visual inspection of low-dimensional embeddings, which are inherently imprecise. Here we present a user-friendly, robust and sensitive k-nearest-neighbor batch-effect test (kBET; […]
Genome-wide association studies (GWAS), relying on hundreds of thousands of individuals, have revealed >200 genomic loci linked to metabolic disease (MD). Loss of insulin sensitivity (IS) is a key component of MD and we hypothesized that discovery of a robust IS transcriptome would help reveal the underlying genomic structure of MD. Using 1,012 human skeletal […]
Mammalian gene expression is inherently stochastic1,2, and results in discrete bursts of RNA molecules that are synthesized from each allele3,4,5,6,7. Although transcription is known to be regulated by promoters and enhancers, it is unclear how cis-regulatory sequences encode transcriptional burst kinetics. Characterization of transcriptional bursting, including the burst size and frequency, has mainly relied on live-cell4,6,8 or […]
The genome is partitioned into topologically associated domains and genomic compartments with shared chromatin valence. This architecture is constrained by the DNA polymer, which precludes interactions between genes on different chromosomes. Here we report a marked divergence from this pattern of nuclear organization that occurs in mouse olfactory sensory neurons. Chromatin conformation capture using in […]