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.
Mapping out the coarse-grained connectivity structures of complex manifolds
Biological systems often change over time, as old cells die and new cells are created through differentiation from progenitor cells. This means that at any given time, not all cells will be at the same stage of development. In this sense, a single-cell sample could contain cells at different stages of differentiation. By analyzing the data, we can identify which cells are at which stages and build a model for their biological transitions.
By quantifying the connectivity of partitions (groups, clusters) of the single-cell graph, partition-based graph abstraction (PAGA) generates a much simpler abstracted graph (PAGA graph) of partitions, in which edge weights represent confidence in the presence of connections.
In this notebook, we will introduce the concept of single-cell Trajectory Analysis using PAGA (Partition-based graph abstraction) in the context of hematopoietic differentiation.
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.
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.
Knowledge of cell type composition in disease relevant tissues is an important step towards the identification of cellular targets of disease. MuSiC is a method that utilizes cell-type specific gene expression from single-cell RNA sequencing (RNA-seq) data to characterize cell type compositions from bulk RNA-seq data in complex tissues.
By appropriate weighting of genes showing cross-subject and cross-cell consistency, MuSiC enables the transfer of cell type-specific gene expression information from one dataset to another.
MuSiC enables the characterization of cellular heterogeneity of complex tissues for understanding of disease mechanisms. As bulk tissue data are more easily accessible than single-cell RNA-seq, MuSiC allows the utilization of the vast amounts of disease relevant bulk tissue RNA-seq data for elucidating cell type contributions in disease.
This notebook provides a walk through tutorial on how to use MuSiC to estimate cell type proportions from bulk sequencing data based on multi-subject single cell data by reproducing the analysis in MuSiC paper, now is published on Nature Communications.