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.

Single-cell RNA-seq datasets in diverse biological and clinical conditions provide great opportunities for the full transcriptional characterization of cell types. However, the integration of these datasets is challeging as they remain biological and techinical differences. **Harmony** is an algorithm allowing fast, sensitive and accurate single-cell data integration.