E-spatial

In this notebook, we present COMMOT (COMMunication analysis by Optimal Transport) to infer cell-cell communication (CCC) in spatial transcriptomic, a package that infers CCC by simultaneously considering numerous ligand–receptor pairs for either spatial transcriptomic data or spatially annotated scRNA-seq data equipped with spatial distances between cells estimated from paired spatial imaging data. A collective optimal transport method is developed to handle complex molecular interactions and spatial constraints. Furthermore, we introduce downstream analysis tools to infer spatial signaling directionality and genes regulated by signaling using machine learning models.

Many spatially resolved transcriptomic technologies do not have single-cell resolution but measure the average gene expression for each spot from a mixture of cells of potentially heterogeneous cell types. Here, we introduce a deconvolution method, conditional autoregressive-based deconvolution (CARD), that combines cell-type-specific expression information from single-cell RNA sequencing (scRNA-seq) with correlation in cell-type composition across tissue locations. Modeling spatial correlation allows us to borrow the cell-type composition information across locations, improving accuracy of deconvolution even with a mismatched scRNA-seq reference. **CARD** can also impute cell-type compositions and gene expression levels at unmeasured tissue locations to enable the construction of a refined spatial tissue map with a resolution arbitrarily higher than that measured in the original study and can perform deconvolution without an scRNA-seq reference. Applications to four datasets, including a pancreatic cancer dataset, identified multiple cell types and molecular markers with distinct spatial localization that define the progression, heterogeneity and compartmentalization of pancreatic cancer.

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.