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Power analyses are considered important factors in designing high-quality experiments. However, such analyses remain a challenge in single-cell RNA-seq studies due to the presence of hierarchical structure within the data (Zimmerman et al., 2021). As cells sampled from the same individual share genetic and environmental backgrounds, these cells are more correlated than cells sampled from different individuals. Currently, most power analyses and hypothesis tests (e.g., differential expression) in scRNA-seq data treat cells as if they were independent, thus ignoring the intra-sample correlation, which could lead to incorrect inferences.
Hierarchicell (Zimmerman, K.D. and Langefeld, C.D., 2021) is an R package proposed to estimate power for testing hypotheses of differential expression in scRNA-seq data while considering the hierarchical correlation structure that exists in the data. The method offers four important categories of functions: data loading and cleaning, empirical estimation of distributions, simulating expression data, and computing type 1 error or power.
In this notebook, we will illustrate an example workflow of Hierarchicell. The notebook is inspired by Hierarchicell's vignette and modified to demonstrate how the tool works on BioTuring's platform.
BioTuring
Cell2location is a principled Bayesian model that can resolve fine-grained cell types in spatial transcriptomic data and create comprehensive cellular maps of diverse tissues. Cell2location accounts for technical sources of variation and borrows statistical strength across locations, thereby enabling the integration of single cell and spatial transcriptomics with higher sensitivity and resolution than existing tools. This is achieved by estimating which combination of cell types in which cell abundance could have given the mRNA counts in the spatial data, while modelling technical effects (platform/technology effect, contaminating RNA, unexplained variance).
This tutorial shows how to use cell2location method for spatially resolving fine-grained cell types by integrating 10X Visium data with scRNA-seq reference of cell types. Cell2location is a principled Bayesian model that estimates which combination of cell types in which cell abundance could have given the mRNA counts in the spatial data, while modelling technical effects (platform/technology effect, contaminating RNA, unexplained variance).
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 transcriptional dynamics, understanding the intricate interplay of regulatory proteins is crucial for deciphering processes ranging from normal development to disease progression. However, traditional RNA velocity methods often overlook the underlying regulatory drivers of gene expression changes over time. This gap in knowledge hinders our ability to unravel the mechanistic intricacies of these dynamic processes.
scKINETICs (Key regulatory Interaction NETwork for Inferring Cell Speed) (Burdziak et al, 2023) offers a dynamic model for gene expression changes that simultaneously learns per-cell transcriptional velocities and a governing gene regulatory network. By employing an expectation-maximization approach, scKINETICS quantifies the impact of each regulatory element on its target genes, incorporating insights from epigenetic data, gene-gene coexpression patterns and constraints dictated by the phenotypic manifold.
Trends
BioTuring
Single-cell sequencing is an increasingly used technology and has promising applications in basic research and clinical translations. However, genotyping methods developed for bulk sequencing data have not been well adapted for single-cell data. In this notebook, we introduce cellSNP-lite for genotyping in single-cell sequencing data for both droplet and well-based platforms.
Cellsnp-lite is a C/C++ tool for efficient genotyping bi-allelic SNPs on single cells. You can use cellsnp-lite after read alignment to obtain the snp x cell pileup UMI or read count matrices for each alleles of given or detected SNPs.
cellSNP-lite aims to pileup the expressed alleles in single-cell or bulk RNA-seq data, which can be directly used for donor deconvolution in multiplexed single-cell RNA-seq data, particularly with vireo, which assigns cells to donors and detects doublets, even without genotyping reference.
Cellsnp-lite has following features:
- Wide applicability: cellsnp-lite can take data from various omics as input, including RNA-seq, DNA-seq, ATAC-seq, either in bulk or single cells.
- Simplified user interface that supports parallel computing, cell barcode and UMI tags.
- High efficiency in terms of running speed and memory usage with highly concordant results compared to existing methods.