E-spatial

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.

Single-cell RNA-seq datasets in diverse biological and clinical conditions provide great opportunities for the full transcriptional characterization of cell types. However, the integration of these datasets is challeging as they remain biological and techinical differences. **Harmony** is an algorithm allowing fast, sensitive and accurate single-cell data integration.

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

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).