Biology subjects

Ben-Kiki, O.

Publications and source records attributed to Ben-Kiki, O..

3 recordsLinked to original sources

bioRxiv2022

Metacell projection for interpretable and quantitative use of transcriptional atlases

We describe MCProj - an algorithm for analyzing query scRNA-seq data by projections over reference single cell atlases. We represent the reference as a manifold consisting of annotated metacell gene expression distributions. We then infer query metacells as mixtures of atlas distributions while correcting for technology-specific gene biases. This approach distinguishes and tags query cells that are consistent with existing atlas states from novel or artifactual behaviors that are not observed in the atlas. It also identifies significant expression differences observed in query states that are mapped coherently onto the atlas. We showcase MCProj functionality by analyzing blood gene expression from multiple sources and technologies, suggesting it as a method of choice for scRNA-seq analysis following extensive cell atlas projects.

bioinformatics↗

bioRxiv2022

Time-Aligned Hourglass Gastrulation Models in Rabbit and Mouse

The hourglass model describes the convergence of species within the same phylum to a similar body plan during development, yet the molecular mechanisms underlying this phenomenon in mammals remain poorly described. Here, we compare rabbit and mouse time-resolved differentiation trajectories to revisit this model at single cell resolution. We modeled gastrulation dynamics using hundreds of embryos sampled between gestation days 6.0-8.5, and compare the species using a new framework for time-resolved single-cell differentiation-flows analysis. We find convergence toward similar cell state compositions at E7.5, underlied by quantitatively conserved expression of 76 transcription factors, despite divergence in surrounding trophoblast and hypoblast signaling. However, we observed noticeable changes in specification timing of some lineages, and divergence of primordial germ cells programs, which in the rabbit do not activate mesoderm genes. Comparative analysis of temporal differentiation models provides a new basis for studying the evolution of gastrulation dynamics across mammals.

evolutionary biology↗

bioRxiv2021

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.

bioinformatics↗