E-spatial

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E-spatial

Single-cell spatial explorer

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Spatially informed cell-type deconvolution for spatial transcriptomics - CARD
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BioTuring

Many spatially resolved transcriptomic technologies do not have single-cell resolution but measure the average gene expression for each spot from a mixture of cells of potentially heterogeneous cell types. Here, we introduce a deconvolution method, conditional autoregressive-based deconvolution (CARD), that combines cell-type-specific expression information from single-cell RNA sequencing (scRNA-seq) with correlation in cell-type composition across tissue locations. Modeling spatial correlation allows us to borrow the cell-type composition information across locations, improving accuracy of deconvolution even with a mismatched scRNA-seq reference. **CARD** can also impute cell-type compositions and gene expression levels at unmeasured tissue locations to enable the construction of a refined spatial tissue map with a resolution arbitrarily higher than that measured in the original study and can perform deconvolution without an scRNA-seq reference. Applications to four datasets, including a pancreatic cancer dataset, identified multiple cell types and molecular markers with distinct spatial localization that define the progression, heterogeneity and compartmentalization of pancreatic cancer.
Only CPU
card
iBRIDGE: A Data Integration Method to Identify Inflamed Tumors from Single-Cell RNAseq Data and Differentiate Cell Type-Specific Markers of Immune-Cell Infiltration
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BioTuring

The development of immune checkpoint-based immunotherapies has been a major advancement in the treatment of cancer, with a subset of patients exhibiting durable clinical responses. A predictive biomarker for immunotherapy response is the pre-existing T-cell infiltration in the tumor immune microenvironment (TIME). Bulk transcriptomics-based approaches can quantify the degree of T-cell infiltration using deconvolution methods and identify additional markers of inflamed/cold cancers at the bulk level. However, bulk techniques are unable to identify biomarkers of individual cell types. Although single-cell RNA sequencing (scRNAseq) assays are now being used to profile the TIME, to our knowledge there is no method of identifying patients with a T-cell inflamed TIME from scRNAseq data. Here, we describe a method, iBRIDGE, which integrates reference bulk RNAseq data with the malignant subset of scRNAseq datasets to identify patients with a T-cell inflamed TIME. Utilizing two datasets with matched bulk data, we show iBRIDGE results correlated highly with bulk assessments (0.85 and 0.9 correlation coefficients). Using iBRIDGE, we identified markers of inflamed phenotypes in malignant cells, myeloid cells, and fibroblasts, establishing type I and type II interferon pathways as dominant signals, especially in malignant and myeloid cells, and finding the TGFβ-driven mesenchymal phenotype not only in fibroblasts but also in malignant cells. Besides relative classification, per-patient average iBRIDGE scores and independent RNAScope quantifications were utilized for threshold-based absolute classification. Moreover, iBRIDGE can be applied to in vitro grown cancer cell lines and can identify the cell lines that are adapted from inflamed/cold patient tumors.
Only CPU
iBRIDGE
CopyKAT: Delineating copy number and clonal substructure in human tumors from single-cell transcriptomes
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BioTuring

Classification of tumor and normal cells in the tumor microenvironment from scRNA-seq data is an ongoing challenge in human cancer study. Copy number karyotyping of aneuploid tumors (***copyKAT***) (Gao, Ruli, et al., 2021) is a method proposed for identifying copy number variations in single-cell transcriptomics data. It is used to predict aneuploid tumor cells and delineate the clonal substructure of different subpopulations that coexist within the tumor mass. In this notebook, we will illustrate a basic workflow of CopyKAT based on the tutorial provided on CopyKAT's repository. We will use a dataset of triple negative cancer tumors sequenced by 10X Chromium 3'-scRNAseq (GSM4476486) as an example. The dataset contains 20,990 features across 1,097 cells. We have modified the notebook to demonstrate how the tool works on BioTuring's platform.
scKINETICS: Inference of regulatory velocity with single-cell transcriptomics data
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BioTuring

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.
Required GPU
scKINETICS

Trends

SpatialData: Visualizations and spatial query on 10x Genomics Visium

BioTuring

SpatialData (Marconato, Luca, et al., 2023) is a framework for processing spatial omics data, including - spatialdata-io: load data from common spatial omics technologies into spatialdata. - spatialdata-plot: static plotting library for spatialdata. - napari-spatialdata: napari plugin for interactive exploration and annotation of spatial data. In this notebook, we will illustrate the visualization functions implemented in SpatialData for Visium data. For datasets from other spatial technologies, please check this document. Also, we will use spatial queries to retrieve all the spatial elements and instances that are within a given rectangular window or polygonal shape from an example Visium brain dataset. The notebook content is inspired from SpatialData's vignette and modified to demonstrate how the tool works on BioTuring's platform.
SpatialData: Deep learning based cell type prediction on image tiles

BioTuring

SpatialData (Marconato, Luca, et al., 2023) is a framework for processing spatial omics data, including spatialdata-io: load data from common spatial omics technologies into spatialdata. spatialdata-plot: static plotting library for spatialdata. napari-spatialdata: napari plugin for interactive exploration and annotation of spatial data. In this notebook, we will illustrate an example to train a Dense Net which predicts cell types Xenium data from an associated H&E image. Particularly, we will access and combine images and annotations across different technologies, where the H&E image from Visium data, and the cell type information from overlapping Xenium data. Also, the two modalities are spatially aligned via an affine transformation. The notebook content is inspired from SpatialData's vignette and modified to demonstrate how the tool works on BioTuring's platform.