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.
scVI-tools (single-cell variational inference tools) is a package for end-to-end analysis of single-cell omics data primarily developed and maintained by the Yosef Lab at UC Berkeley. scvi-tools has two components
- Interface for easy use of a range of probabilistic models for single-cell omics (e.g., scVI, scANVI, totalVI).
- Tools to build new probabilistic models, which are powered by PyTorch, PyTorch Lightning, and Pyro.
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.
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. (More)