CellChat

In the realm of cancer research, grasping the intricacies of intratumor heterogeneity and its interplay with the immune system is paramount for deciphering treatment resistance and tumor progression. While single-cell RNA sequencing unveils diverse transcriptional programs, the challenge persists in automatically discerning malignant cells from non-malignant ones within complex datasets featuring varying coverage depths. Thus, there arises a compelling need for an automated solution to this classification conundrum. SCEVAN (De Falco et al., 2023), a variational algorithm, is designed to autonomously identify the clonal copy number substructure of tumors using single-cell data. It automatically separates malignant cells from non-malignant ones, and subsequently, groups of malignant cells are examined through an optimization-driven joint segmentation process.

Single-cell RNA sequencing (scRNA-seq) data often encountered technical artifacts called "doublets" which are two cells that are sequenced under the same cellular barcode. Doublets formed from different cell types or states are called heterotypic and homotypic otherwise. These factors constrain cell throughput and may result in misleading biological interpretations. DoubletFinder (McGinnis, Murrow, and Gartner 2019) is one of the methods proposed for doublet detection. In this notebook, we will illustrate an example workflow of DoubletFinder. We use a 10x Genomics dataset which captures peripheral blood mononuclear cells (PBMCs) from a healthy donor stained with a panel of 31 TotalSeq™-B antibodies (BioLegend).

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.

Single-cell RNA sequencing (scRNA-seq) data have allowed us to investigate cellular heterogeneity and the kinetics of a biological process. Some studies need to understand how cells change state, and corresponding genes during the process, but it is challenging to track the cell development in scRNA-seq protocols. Therefore, a variety of statistical and computational methods have been proposed for lineage inference (or pseudotemporal ordering) to reconstruct the states of cells according to the developmental process from the measured snapshot data. Specifically, lineage refers to an ordered transition of cellular states, where individual cells represent points along. pseudotime is a one-dimensional variable representing each cell’s transcriptional progression toward the terminal state. Slingshot which is one of the methods suggested for lineage reconstruction and pseudotime inference from single-cell gene expression data. In this notebook, we will illustrate an example workflow for cell lineage and pseudotime inference using Slingshot. The notebook is inspired by Slingshot's vignette and modified to demonstrate how the tool works on BioTuring's platform.