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BioTuring
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.
BioTuring
Many spatially resolved transcriptomic technologies do not have single-cell resolution but measure the average gene expression for each spot from a mixture of cells of potentially heterogeneous cell types.
Here, we introduce a deconvolution method, conditional autoregressive-based deconvolution (CARD), that combines cell-type-specific expression information from single-cell RNA sequencing (scRNA-seq) with correlation in cell-type composition across tissue locations. Modeling spatial correlation allows us to borrow the cell-type composition information across locations, improving accuracy of deconvolution even with a mismatched scRNA-seq reference.
**CARD** can also impute cell-type compositions and gene expression levels at unmeasured tissue locations to enable the construction of a refined spatial tissue map with a resolution arbitrarily higher than that measured in the original study and can perform deconvolution without an scRNA-seq reference.
Applications to four datasets, including a pancreatic cancer dataset, identified multiple cell types and molecular markers with distinct spatial localization that define the progression, heterogeneity and compartmentalization of pancreatic cancer.
BioTuring
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.
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.
Trends
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