A divide and conquer metacell algorithm for scalable scRNA-seq analysis

Scaling scRNA-seq to profile millions of cells is increasingly feasible. Such data is crucial for the construction of high-resolution maps of transcriptional manifolds. But current analysis strategies, in particular dimensionality reduction and two-phase clustering, offers only limited scaling and sensitivity to define such manifolds. Here we introduce Metacell-2, a recursive divide and conquer algorithm allowing efficient decomposition of scRNA-seq datasets of any size into small and cohesive groups of cells denoted as metacells. We show the algorithm outperforms current solutions in time, memory and quality. Importantly, Metacell-2 also improves outlier cell detection and rare cell type identification, as we exemplify by analysis of human bone marrow cell atlas and mouse embryonic data. Metacell-2 is implemented over the scanpy framework for easy integration in any analysis pipeline.

Olfactory Rod Cells: A Rare Cell Type in the Larval Zebrafish Olfactory Epithelium With a Large Actin-Rich Apical Projection

We report the presence of a rare cell type, the olfactory rod cell, in the developing zebrafish olfactory epithelium. These cells each bear a single actin-rich rod-like apical projection extending 5–10 μm from the epithelial surface. Live imaging with a ubiquitous Lifeact-RFP label indicates that the olfactory rods can oscillate. Olfactory rods arise within a few hours of the olfactory pit opening, increase in numbers and size during larval stages, and can develop in the absence of olfactory cilia. Olfactory rod cells differ in morphology from the known classes of olfactory sensory neuron, but express reporters driven by neuronal promoters. A sub-population of olfactory rod cells expresses a Lifeact-mRFPruby transgene driven by thesox10promoter. Mosaic expression of this transgene reveals that olfactory rod cells have rounded cell bodies located apically in the olfactory epithelium and have no detectable axon. We offer speculation on the possible function of these cells in the Discussion.

Scalpel: Information-based Dimensionality Reduction for Rare Cell Type Discovery

Single-cell RNA-sequencing (scRNA-seq) enables discovery of clinically and biologically interesting populations, but detecting rare cell types is a persistent challenge. Here we introduce Scalpel, a novel technique for extracting interpretable and maximally informative features from single-cell data, enabling population discovery, batch correction, and other downstream analyses at unprecedented resolution. On a collection of cytotoxic T-cells, Scalpel recovers subtle and biologically important populations, including gamma-delta T-cells and MAIT cells, which are invisible to standard pipelines. In multi-batched data, Scalpel effectively removes systemic batch effects, achieving robust and state-of-the-art performance. Unlike other methods, Scalpel is completely unsupervised, human-interpretable, and applicable to both continuous trajectories and clustered data, making it suitable in a wide range of analytic settings.

Olfactory rod cells: a rare cell type in the larval zebrafish olfactory epithelium with an actin-rich apical projection

We report the presence of a rare cell type, the olfactory rod cell, in the developing zebrafish olfactory epithelium. These cells each bear a single actin-rich rod-like apical projection extending about 10 μm from the epithelial surface. Live imaging with a ubiquitous Lifeact-RFP label indicates that the rods can oscillate. Olfactory rods arise within a few hours of the olfactory pit opening, increase in numbers and size during larval stages, and can develop in the absence of olfactory cilia. Olfactory rod cells differ in morphology from the known classes of olfactory sensory neuron, but express reporters driven by neuronal promoters. The cells also differ from secondary sensory cells such as hair cells of the inner ear or lateral line, or sensory cells in the taste bud, as they are not associated with established synaptic terminals. A sub-population of olfactory rod cells expresses a Lifeact-mRFPruby transgene driven by the sox10 promoter. Mosaic expression of this transgene reveals that olfactory rod cells have rounded cell bodies located apically in the olfactory epithelium.

GiniClust3: a fast and memory-efficient tool for rare cell type identification

MotivationWith the rapid development of single-cell RNA sequencing technology, it is possible to dissect cell-type composition at high resolution. A number of methods have been developed with the purpose to identify rare cell types. However, existing methods are still not scalable to large datasets, limiting their utility. To overcome this limitation, we present a new software package, called GiniClust3, which is an extension of GiniClust2 and significantly faster and memory-efficient than previous versions.ResultsUsing GiniClust3, it only takes about 7 hours to identify both common and rare cell clusters from a dataset that contains more than one million cells. Cell type mapping and perturbation analyses show that GiniClust3 could robustly identify cell clusters.AvailabilityGiniCluster3 is implemented in the open-source python package, with source code freely available through the Github (https://github.com/rdong08/GiniClust3)[email protected] informationSupplementary data are available at Bioinformatics online.