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.

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.