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Single-cell RNA data allows cell-cell communications (***CCC***) methods to infer CCC at either the individual cell or cell cluster/cell type level, but physical distances between cells are not preserved Almet, Axel A., et al., (2021). On the other hand, spatial data provides spatial distances between cells, but single-cell or gene resolution is potentially lost. Therefore, integrating two types of data in a proper manner can complement their strengths and limitations, from that improve CCC analysis.
In this pipeline, we analyze CCC on Visium data with single-cell data as a reference. The pipeline includes 4 sub-notebooks as following
01-deconvolution: This step involves deconvolution and cell type annotation for Visium data, with cell type information obtained from a relevant single-cell dataset. The deconvolution method is SpatialDWLS which is integrated in Giotto package.
02-giotto: performs spatial based CCC and expression based CCC on Visium data using Giotto method.
03-nichenet: performs spatial based CCC and expression based CCC on Visium data using NicheNet method.
04-visualization: visualizes CCC results obtained from Giotto and NicheNet.
BioTuring
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.
BioTuring
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.
BioTuring
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.
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BioTuring
scGen is a generative model to predict single-cell perturbation response across cell types, studies and species (Nature Methods, 2019). scGen is implemented using the scvi-tools framework.
What you can do with scGen:
Train on a dataset with multiple cell types and conditions and predict the perturbation effect on the cell type which you only have in one condition. This scenario can be extended to multiple species where you want to predict the effect of a specific species using another or all the species.
Train on a dataset where you have two conditions (e.g. control and perturbed) and predict on second dataset with similar genes.
Remove batch effect on labeled data. In this scenario you need to provide cell_type and batch labels to the method. Note that batch_removal does not require all cell types to be present in all datasets (batches). If you have dataset specific cell type it will preserved as before.
We assume there exist two conditions in you dataset (e.g. control and perturbed). You can train the model and with your data and predict the perturbation for the cell type/species of interest.
We recommend to use normalized data for the training. A simple example for normalization can be performed using scanpy