scVI-tools (single-cell variational inference tools) is a package for end-to-end analysis of single-cell omics data primarily developed and maintained by the Yosef Lab at UC Berkeley. scvi-tools has two components
- Interface for easy use of a range of probabilistic models for single-cell omics (e.g., scVI, scANVI, totalVI).
- Tools to build new probabilistic models, which are powered by PyTorch, PyTorch Lightning, and Pyro.
Spatial transcriptomic studies are becoming increasingly common and large, posing important statistical and computational challenges for many analytic tasks. Here, we present SPARK-X, a non-parametric method for rapid and effective detection of spatially expressed genes in large spatial transcriptomic studies.
SPARK-X not only produces effective type I error control and high power but also brings orders of magnitude computational savings. We apply SPARK-X to analyze three large datasets, one of which is only analyzable by SPARK-X. In these data, SPARK-X identifies many spatially expressed genes including those that are spatially expressed within the same cell type, revealing new biological insights.
Cell2location is a principled Bayesian model that can resolve fine-grained cell types in spatial transcriptomic data and create comprehensive cellular maps of diverse tissues. Cell2location accounts for technical sources of variation and borrows statistical strength across locations, thereby enabling the integration of single cell and spatial transcriptomics with higher sensitivity and resolution than existing tools. This is achieved by estimating which combination of cell types in which cell abundance could have given the mRNA counts in the spatial data, while modelling technical effects (platform/technology effect, contaminating RNA, unexplained variance).
This tutorial shows how to use cell2location method for spatially resolving fine-grained cell types by integrating 10X Visium data with scRNA-seq reference of cell types. Cell2location is a principled Bayesian model that estimates which combination of cell types in which cell abundance could have given the mRNA counts in the spatial data, while modelling technical effects (platform/technology effect, contaminating RNA, unexplained variance).
In the realm of transcriptional dynamics, understanding the intricate interplay of regulatory proteins is crucial for deciphering processes ranging from normal development to disease progression. However, traditional RNA velocity methods often overlook the underlying regulatory drivers of gene expression changes over time. This gap in knowledge hinders our ability to unravel the mechanistic intricacies of these dynamic processes.
scKINETICs (Key regulatory Interaction NETwork for Inferring Cell Speed) (Burdziak et al, 2023) offers a dynamic model for gene expression changes that simultaneously learns per-cell transcriptional velocities and a governing gene regulatory network. By employing an expectation-maximization approach, scKINETICS quantifies the impact of each regulatory element on its target genes, incorporating insights from epigenetic data, gene-gene coexpression patterns and constraints dictated by the phenotypic manifold.
Cell–cell communication mediated by ligand–receptor complexes is critical to coordinating diverse biological processes, such as development, differentiation and inflammation.
To investigate how the context-dependent crosstalk of different cell types enables physiological processes to proceed, we developed CellPhoneDB, a novel repository of ligands, receptors and their interactions. In contrast to other repositories, our database takes into account the subunit architecture of both ligands and receptors, representing heteromeric complexes accurately.
We integrated our resource with a statistical framework that predicts enriched cellular interactions between two cell types from single-cell transcriptomics data. Here, we outline the structure and content of our repository, provide procedures for inferring cell–cell communication networks from single-cell RNA sequencing data and present a practical step-by-step guide to help implement the protocol.
CellPhoneDB v.2.0 is an updated version of our resource that incorporates additional functionalities to enable users to introduce new interacting molecules and reduces the time and resources needed to interrogate large datasets.
CellPhoneDB v.2.0 is publicly available, both as code and as a user-friendly web interface; it can be used by both experts and researchers with little experience in computational genomics.
In our protocol, we demonstrate how to evaluate meaningful biological interactions with CellPhoneDB v.2.0 using published datasets. This protocol typically takes ~2 h to complete, from installation to statistical analysis and visualization, for a dataset of ~10 GB, 10,000 cells and 19 cell types, and using five threads.