Tumors are complex tissues of cancerous cells surrounded by a heterogeneous cellular microenvironment with which they interact. Single-cell sequencing enables molecular characterization of single cells within the tumor. However, cell annotation—the assignment of cell type or cell state to each sequenced cell—is a challenge, especially identifying tumor cells within single-cell or spatial sequencing experiments.
Here, we propose ikarus, a machine learning pipeline aimed at distinguishing tumor cells from normal cells at the single-cell level. We test ikarus on multiple single-cell datasets, showing that it achieves high sensitivity and specificity in multiple experimental contexts.
**InferCNV** is a Bayesian method, which agglomerates the expression signal of genomically adjointed genes to ascertain whether there is a gain or loss of a certain larger genomic segment. We have used **inferCNV** to call copy number variations in all samples used in the manuscript.
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.
The development of large-scale single-cell atlases has allowed describing cell states in a more detailed manner. Meanwhile, current deep leanring methods enable rapid analysis of newly generated query datasets by mapping them into reference atlases.
expiMap (‘explainable programmable mapper’) Lotfollahi, Mohammad, et al. is one of the methods proposed for single-cell reference mapping. Furthermore, it incorporates prior knowledge from gene sets databases or users to analyze query data in the context of known gene programs (GPs).
Spatial transcriptomic studies are becoming increasingly common and large, posing important statistical and computational challenges for many analytic tasks. Here, we present SPARK-X, a non-parametric method for rapid and effective detection of spatially expressed genes in large spatial transcriptomic studies.
SPARK-X not only produces effective type I error control and high power but also brings orders of magnitude computational savings. We apply SPARK-X to analyze three large datasets, one of which is only analyzable by SPARK-X. In these data, SPARK-X identifies many spatially expressed genes including those that are spatially expressed within the same cell type, revealing new biological insights.
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