Recent technological advancements have enabled spatially resolved transcriptomic profiling but at multi-cellular pixel resolution, thereby hindering the identification of cell-type-specific spatial patterns and gene expression variation.
To address this challenge, we develop STdeconvolve as a reference-free approach to deconvolve underlying cell types comprising such multi-cellular pixel resolution spatial transcriptomics (ST) datasets. Using simulated as well as real ST datasets from diverse spatial transcriptomics technologies comprising a variety of spatial resolutions such as Spatial Transcriptomics, 10X Visium, DBiT-seq, and Slide-seq, we show that STdeconvolve can effectively recover cell-type transcriptional profiles and their proportional representation within pixels without reliance on external single-cell transcriptomics references.
**STdeconvolve** provides comparable performance to existing reference-based methods when suitable single-cell references are available, as well as potentially superior performance when suitable single-cell references are not available.
STdeconvolve is available as an open-source R software package with the source code available at https://github.com/JEFworks-Lab/STdeconvolve .
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.
CellRank2 (Weiler et al, 2023) is a powerful framework for studying cellular fate using single-cell RNA sequencing data. It can handle millions of cells and different data types efficiently. This tool can identify cell fate and probabilities across various data sets. It also allows for analyzing transitions over time and uncovering key genes in developmental processes. Additionally, CellRank2 estimates cell-specific transcription and degradation rates, aiding in understanding differentiation trajectories and regulatory mechanisms.
In this notebook, we will use a primary tumor sample of patient T71 from the dataset GSE137804 (Dong R. et al, 2020) as an example. We have performed RNA-velocity analysis and pseudotime calculation on this dataset in scVelo (Bergen et al, 2020) notebook. The output will be then loaded into this CellRank2 notebook for further analysis.
This notebook is based on the tutorial provided on CellRank2 documentation. We have modified the notebook and changed the input data to show how the tool works on BioTuring's platform.
Advances in multi-omics have led to an explosion of multimodal datasets to address questions from basic biology to translation. While these data provide novel opportunities for discovery, they also pose management and analysis challenges, thus motivating the development of tailored computational solutions. `muon` is a Python framework for multimodal omics.
It introduces multimodal data containers as `MuData` object. The package also provides state of the art methods for multi-omics data integration. `muon` allows the analysis of both unimodal omics and multimodal omics.
This notebook provides an overview of the Bioconductor package edgeR for differential expression analyses of read counts arising from RNA-Seq, SAGE or similar technologies. The package can be applied to any technology that produces read counts for genomic features.
edgeR implements statistical methods based on generalized linear models (glms), suitable for multifactor experiments of any complexity. The glm functions can test for differential expression using either likelihood ratio tests or quasi-likelihood F-tests.
A particular feature of edgeR functionality, both classic and glm, are empirical Bayes methods that permit the estimation of gene-specific biological variation, even for experiments with minimal levels of biological replication.
edgeR can be applied to differential expression at the gene, exon, transcript or tag level. In fact, read counts can be summarized by any genomic feature. edgeR analyses at the exon level are easily extended to detect differential splicing or isoform-specific differential expression.