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.
InferCNV is used to explore tumor single cell RNA-Seq data to identify evidence for somatic large-scale chromosomal copy number alterations, such as gains or deletions of entire chromosomes or large segments of chromosomes. This is done by exploring expression intensity of genes across positions of tumor genome in comparison to a set of reference 'normal' cells. A heatmap is generated illustrating the relative expression intensities across each chromosome, and it often becomes readily apparent as to which regions of the tumor genome are over-abundant or less-abundant as compared to that of normal cells.
**Infercnvpy** is a scalable python library to infer copy number variation (CNV) events from single cell transcriptomics data. It is heavliy inspired by InferCNV, but plays nicely with scanpy and is much more scalable.
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
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.
scPRINT is a large transformer model built for the inference of gene networks (connections between genes explaining the cell's expression profile) from scRNAseq data.
It uses novel encoding and decoding of the cell expression profile and new pre-training methodologies to learn a cell model.
scPRINT can be used to perform the following analyses:
- expression denoising: increase the resolution of your scRNAseq data
- cell embedding: generate a low-dimensional representation of your dataset
- label prediction: predict the cell type, disease, sequencer, sex, and ethnicity of your cells
- gene network inference: generate a gene network from any cell or cell cluster in your scRNAseq dataset