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Identifying tumor cells at the single-cell level using machine learning - inferCNV
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BioTuring

Tumors are complex tissues of cancerous cells surrounded by a heterogeneous cellular microenvironment with which they interact. Single-cell sequencing enables molecular characterization of single cells within the tumor. However, cell annotation—the assignment of cell type or cell state to each sequenced cell—is a challenge, especially identifying tumor cells within single-cell or spatial sequencing experiments. Here, we propose ikarus, a machine learning pipeline aimed at distinguishing tumor cells from normal cells at the single-cell level. We test ikarus on multiple single-cell datasets, showing that it achieves high sensitivity and specificity in multiple experimental contexts. **InferCNV** is a Bayesian method, which agglomerates the expression signal of genomically adjointed genes to ascertain whether there is a gain or loss of a certain larger genomic segment. We have used **inferCNV** to call copy number variations in all samples used in the manuscript.
Only CPU
inferCNV
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
ADImpute: Adaptive Dropout Imputer
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BioTuring

Single-cell RNA sequencing (scRNA-seq) protocols often face challenges in measuring the expression of all genes within a cell due to various factors, such as technical noise, the sensitivity of scRNA-seq techniques, or sample quality. This limitation gives rise to a need for the prediction of unmeasured gene expression values (also known as dropout imputation) from scRNA-seq data. ADImpute (Leote A, 2023) is an R package combining several dropout imputation methods, including two existing methods (DrImpute, SAVER), two novel implementations: Network, a gene regulatory network-based approach using gene-gene relationships learned from external data, and Baseline, a method corresponding to a sample-wide average.. This notebook is to illustrate an example workflow of ADImpute on sample datasets loaded from the package. The notebook content is inspired from ADImpute's vignette and modified to demonstrate how the tool works on BioTuring's platform.
Only CPU
ADImpute
SPARK-X: non-parametric modeling enables scalable and robust detection of spatial expression patterns for large spatial transcriptomic studies
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BioTuring

Spatial transcriptomic studies are becoming increasingly common and large, posing important statistical and computational challenges for many analytic tasks. Here, we present SPARK-X, a non-parametric method for rapid and effective detection of spatially expressed genes in large spatial transcriptomic studies. SPARK-X not only produces effective type I error control and high power but also brings orders of magnitude computational savings. We apply SPARK-X to analyze three large datasets, one of which is only analyzable by SPARK-X. In these data, SPARK-X identifies many spatially expressed genes including those that are spatially expressed within the same cell type, revealing new biological insights.
Only CPU
SPARK-X

Trends

scPRINT: Large Cell Model for scRNAseq data

BioTuring

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
Required GPU
scPrint