E-spatial

Understanding global communications among cells requires accurate representation of cell-cell signaling links and effective systems-level analyses of those links. We construct a database of interactions among ligands, receptors and their cofactors that accurately represent known heteromeric molecular complexes. We then develop **CellChat**, a tool that is able to quantitatively infer and analyze intercellular communication networks from single-cell RNA-sequencing (scRNA-seq) data. CellChat predicts major signaling inputs and outputs for cells and how those cells and signals coordinate for functions using network analysis and pattern recognition approaches. Through manifold learning and quantitative contrasts, CellChat classifies signaling pathways and delineates conserved and context-specific pathways across different datasets. Applying **CellChat** to mouse and human skin datasets shows its ability to extract complex signaling patterns.

Spatial transcriptomics (ST) technology has allowed to capture of topographical gene expression profiling of tumor tissues, but single-cell resolution is potentially lost. Identifying cell identities in ST datasets from tumors or other samples remains challenging for existing cell-type deconvolution methods. Spatial Cellular Estimator for Tumors (SpaCET) is an R package for analyzing cancer ST datasets to estimate cell lineages and intercellular interactions in the tumor microenvironment. Generally, SpaCET infers the malignant cell fraction through a gene pattern dictionary, then calibrates local cell densities and determines immune and stromal cell lineage fractions using a constrained regression model. Finally, the method can reveal putative cell-cell interactions in the tumor microenvironment. In this notebook, we will illustrate an example workflow for cell type deconvolution and interaction analysis on breast cancer ST data from 10X Visium. The notebook is inspired by SpaCET's vignettes and modified to demonstrate how the tool works on BioTuring's platform.

Expanded CRISPR-compatible CITE-seq (ECCITE-seq) which is built upon pooled CRISPR screens, allows to simultaneously measure transcriptomes, surface protein levels, and single-guide RNA (sgRNA) sequences at single-cell resolution. The technique enables multimodal characterization of each perturbation and effect exploration. However, it also encounters heterogeneity and complexity which can cause substantial noise into downstream analyses. Mixscape (Papalexi, Efthymia, et al., 2021) is a computational framework proposed to substantially improve the signal-to-noise ratio in single-cell perturbation screens by identifying and removing confounding sources of variation. In this notebooks, we demonstrate Mixscape's features using pertpy - a Python package offering a range of tools for perturbation analysis. The original pipeline of Mixscape implemented in R can be found here.

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.