E-spatial

Geneformer is a foundation transformer model pretrained on a large-scale corpus of ~30 million single cell transcriptomes to enable context-aware predictions in settings with limited data in network biology. Here, we will demonstrate a basic workflow to work with ***Geneformer*** models. These notebooks include the instruction to: 1. Prepare input datasets 2. Finetune Geneformer model to perform specific task 3. Using finetuning models for cell classification and gene classification application

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.

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.

The recent development of single-cell RNA-sequencing (scRNA-seq) technology has enabled us to infer cell-type-specific co-expression networks, enhancing our understanding of cell-type-specific biological functions. However, existing methods proposed for this task still face challenges due to unique characteristics in scRNA-seq data, such as high sequencing depth variations across cells and measurement errors. CS-CORE (Su, C., Xu, Z., Shan, X. et al., 2023), an R package for cell-type-specific co-expression inference, explicitly models sequencing depth variations and measurement errors in scRNA-seq data. In this notebook, we will illustrate an example workflow of CS-CORE using a dataset of Peripheral Blood Mononuclear Cells (PBMC) from COVID patients and healthy controls (Wilk et al., 2020). The notebook content is inspired by CS-CORE's vignette and modified to demonstrate how the tool works on BioTuring's platform.