The recent development of experimental methods for measuring chromatin state at single-cell resolution has created a need for computational tools capable of analyzing these datasets. Here we developed Signac, a framework for the analysis of single-cell chromatin data, as an extension of the Seurat R toolkit for single-cell multimodal analysis.
**Signac** enables an end-to-end analysis of single-cell chromatin data, including peak calling, quantification, quality control, dimension reduction, clustering, integration with single-cell gene expression datasets, DNA motif analysis, and interactive visualization.
Furthermore, Signac facilitates the analysis of multimodal single-cell chromatin data, including datasets that co-assay DNA accessibility with gene expression, protein abundance, and mitochondrial genotype. We demonstrate scaling of the Signac framework to datasets containing over 700,000 cells.
Computational methods that model how the gene expression of a cell is influenced by interacting cells are lacking.
We present NicheNet, a method that predicts ligand–target links between interacting cells by combining their expression data with prior knowledge of signaling and gene regulatory networks.
We applied NicheNet to the tumor and immune cell microenvironment data and demonstrated that NicheNet can infer active ligands and their gene regulatory effects on interacting cells.
Mapping out the coarse-grained connectivity structures of complex manifolds
Biological systems often change over time, as old cells die and new cells are created through differentiation from progenitor cells. This means that at any given time, not all cells will be at the same stage of development. In this sense, a single-cell sample could contain cells at different stages of differentiation. By analyzing the data, we can identify which cells are at which stages and build a model for their biological transitions.
By quantifying the connectivity of partitions (groups, clusters) of the single-cell graph, partition-based graph abstraction (PAGA) generates a much simpler abstracted graph (PAGA graph) of partitions, in which edge weights represent confidence in the presence of connections.
In this notebook, we will introduce the concept of single-cell Trajectory Analysis using PAGA (Partition-based graph abstraction) in the context of hematopoietic differentiation.
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.
scGen is a generative model to predict single-cell perturbation response across cell types, studies and species (Nature Methods, 2019). scGen is implemented using the scvi-tools framework.
What you can do with scGen:
Train on a dataset with multiple cell types and conditions and predict the perturbation effect on the cell type which you only have in one condition. This scenario can be extended to multiple species where you want to predict the effect of a specific species using another or all the species.
Train on a dataset where you have two conditions (e.g. control and perturbed) and predict on second dataset with similar genes.
Remove batch effect on labeled data. In this scenario you need to provide cell_type and batch labels to the method. Note that batch_removal does not require all cell types to be present in all datasets (batches). If you have dataset specific cell type it will preserved as before.
We assume there exist two conditions in you dataset (e.g. control and perturbed). You can train the model and with your data and predict the perturbation for the cell type/species of interest.
We recommend to use normalized data for the training. A simple example for normalization can be performed using scanpy