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) protocols often face challenges in measuring the expression of all genes within a cell due to various factors, such as technical noise, the sensitivity of scRNA-seq techniques, or sample quality. This limitation gives rise to a need for the prediction of unmeasured gene expression values (also known as dropout imputation) from scRNA-seq data.
ADImpute (Leote A, 2023) is an R package combining several dropout imputation methods, including two existing methods (DrImpute, SAVER), two novel implementations: Network, a gene regulatory network-based approach using gene-gene relationships learned from external data, and Baseline, a method corresponding to a sample-wide average..
This notebook is to illustrate an example workflow of ADImpute on sample datasets loaded from the package. The notebook content is inspired from ADImpute's vignette and modified to demonstrate how the tool works on BioTuring's platform.
Doublets are a characteristic error source in droplet-based single-cell sequencing data where two cells are encapsulated in the same oil emulsion and are tagged with the same cell barcode. Across type doublets manifest as fictitious phenotypes that can be incorrectly interpreted as novel cell types. DoubletDetection present a novel, fast, unsupervised classifier to detect across-type doublets in single-cell RNA-sequencing data that operates on a count matrix and imposes no experimental constraints.
This classifier leverages the creation of in silico synthetic doublets to determine which cells in the
input count matrix have gene expression that is best explained by the combination of distinct cell
types in the matrix.
In this notebook, we will illustrate an example workflow for detecting doublets in single-cell RNA-seq count matrices.
Single-cell RNA sequencing methods can profile the transcriptomes of single cells but cannot preserve spatial information. Conversely, spatial transcriptomics assays can profile spatial regions in tissue sections but do not have single-cell resolution.
Here, Runmin Wei (Siyuan He, Shanshan Bai, Emi Sei, Min Hu, Alastair Thompson, Ken Chen, Savitri Krishnamurthy & Nicholas E. Navin) developed a computational method called CellTrek that combines these two datasets to achieve single-cell spatial mapping through coembedding and metric learning approaches. They benchmarked CellTrek using simulation and in situ hybridization datasets, which demonstrated its accuracy and robustness.
They then applied CellTrek to existing mouse brain and kidney datasets and showed that CellTrek can detect topological patterns of different cell types and cell states. They performed single-cell RNA sequencing and spatial transcriptomics experiments on two ductal carcinoma in situ tissues and applied CellTrek to identify tumor subclones that were restricted to different ducts, and specific T-cell states adjacent to the tumor areas.
Recent spatial transcriptomics (ST) technologies have allowed us to capture cellular heterogeneity while retaining spatial information. However, ST datasets may lose single-cell resolution, limiting the discovery of cell-type-specific spatial patterns of localization and expression.
spacexr (Spatial-eXpression-R) is an R package providing two methods, i.e., Robust Cell Type Decomposition (RCTD) (Cable, Dylan M., et al., 2022) and Cell type-Specific Inference of Differential Expression (C-SIDE) (Cable, Dylan M., et al., 2022) for ST data. RCTD is proposed for cell type deconvolution, while leveraging references from another annotated single-cell RNA-seq data. C-SIDE identifies cell type-specific differential expression, accounting for localization of other cell types.
We will illustrate an example workflow in two notebooks, RCTD and C-SIDE, on a hippocampus Visium dataset provided by the authors. The notebooks are inspired from spacexr's vignettes and modified to demonstrate how the tool works on BioTuring's platform.