In the realm of cancer research, grasping the intricacies of intratumor heterogeneity and its interplay with the immune system is paramount for deciphering treatment resistance and tumor progression. While single-cell RNA sequencing unveils diverse transcriptional programs, the challenge persists in automatically discerning malignant cells from non-malignant ones within complex datasets featuring varying coverage depths. Thus, there arises a compelling need for an automated solution to this classification conundrum.
SCEVAN (De Falco et al., 2023), a variational algorithm, is designed to autonomously identify the clonal copy number substructure of tumors using single-cell data. It automatically separates malignant cells from non-malignant ones, and subsequently, groups of malignant cells are examined through an optimization-driven joint segmentation process.
Spatial transcriptomics (ST) technology has allowed to capture of topographical gene expression profiling of tumor tissues, but single-cell resolution is potentially lost. Identifying cell identities in ST datasets from tumors or other samples remains challenging for existing cell-type deconvolution methods.
Spatial Cellular Estimator for Tumors (SpaCET) is an R package for analyzing cancer ST datasets to estimate cell lineages and intercellular interactions in the tumor microenvironment. Generally, SpaCET infers the malignant cell fraction through a gene pattern dictionary, then calibrates local cell densities and determines immune and stromal cell lineage fractions using a constrained regression model. Finally, the method can reveal putative cell-cell interactions in the tumor microenvironment.
In this notebook, we will illustrate an example workflow for cell type deconvolution and interaction analysis on breast cancer ST data from 10X Visium. The notebook is inspired by SpaCET's vignettes and modified to demonstrate how the tool works on BioTuring's platform.
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 .
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.
Reconstructing cell type compositions and their gene expression from bulk RNA sequencing (RNA-seq) datasets is an ongoing challenge in cancer research. BayesPrism (Chu, T., Wang, Z., Pe’er, D. et al., 2022) is a Bayesian method used to predict cellular composition and gene expression in individual cell types from bulk RNA-seq datasets, with scRNA-seq as references.
This notebook illustrates an example workflow for bulk RNA-seq deconvolution using BayesPrism. The notebook content is inspired by BayesPrism's vignette and modified to demonstrate how the tool works on BioTuring's platform.