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CellPhoneDB: inferring cell–cell communication from combined expression of multi-subunit ligand–receptor complexes
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BioTuring

Cell–cell communication mediated by ligand–receptor complexes is critical to coordinating diverse biological processes, such as development, differentiation and inflammation. To investigate how the context-dependent crosstalk of different cell types enables physiological processes to proceed, we developed CellPhoneDB, a novel repository of ligands, receptors and their interactions. In contrast to other repositories, our database takes into account the subunit architecture of both ligands and receptors, representing heteromeric complexes accurately. We integrated our resource with a statistical framework that predicts enriched cellular interactions between two cell types from single-cell transcriptomics data. Here, we outline the structure and content of our repository, provide procedures for inferring cell–cell communication networks from single-cell RNA sequencing data and present a practical step-by-step guide to help implement the protocol. CellPhoneDB v.2.0 is an updated version of our resource that incorporates additional functionalities to enable users to introduce new interacting molecules and reduces the time and resources needed to interrogate large datasets. CellPhoneDB v.2.0 is publicly available, both as code and as a user-friendly web interface; it can be used by both experts and researchers with little experience in computational genomics. In our protocol, we demonstrate how to evaluate meaningful biological interactions with CellPhoneDB v.2.0 using published datasets. This protocol typically takes ~2 h to complete, from installation to statistical analysis and visualization, for a dataset of ~10 GB, 10,000 cells and 19 cell types, and using five threads.
Only CPU
CellPhoneDB
COMMOT: Screening cell-cell communication in spatial transcriptomics via collective optimal transport
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BioTuring

In this notebook, we present COMMOT (COMMunication analysis by Optimal Transport) to infer cell-cell communication (CCC) in spatial transcriptomic, a package that infers CCC by simultaneously considering numerous ligand–receptor pairs for either spatial transcriptomic data or spatially annotated scRNA-seq data equipped with spatial distances between cells estimated from paired spatial imaging data. A collective optimal transport method is developed to handle complex molecular interactions and spatial constraints. Furthermore, we introduce downstream analysis tools to infer spatial signaling directionality and genes regulated by signaling using machine learning models.
Only CPU
COMMOT
NicheNet: modeling intercellular communication by linking ligands to target genes
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BioTuring

Computational methods that model how the gene expression of a cell is influenced by interacting cells are lacking. We present NicheNet, a method that predicts ligand–target links between interacting cells by combining their expression data with prior knowledge of signaling and gene regulatory networks. We applied NicheNet to the tumor and immune cell microenvironment data and demonstrated that NicheNet can infer active ligands and their gene regulatory effects on interacting cells.
Only CPU
nichenetr
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

Trends

PROST: A quantitative pattern recognition framework for spatial transcriptomics

BioTuring

Computational methods have been proposed to leverage spatially resolved transcriptomic data, pinpointing genes with spatial expression patterns and delineating tissue domains. However, existing approaches fall short in uniformly quantifying spatially variable genes (SVGs). Moreover, from a methodological viewpoint, while SVGs are naturally associated with depicting spatial domains, they are technically dissociated in most methods. Here, PROST is a flexible framework to quantify gene spatial expression patterns and detect spatial tissue domains using spatially resolved transcriptomics with various resolutions. PROST consists of two independent workflows: PROST Index (PI) and PROST Neural Network (PNN). Using PROST you can do: * Quantitative identification of spatial patterns of gene expression changes by the proposed PROST Index (PI). * Unsupervised identification of spatial tissue domains using a PROST Neural Network (PNN) via a self-attention mechanism.
Required GPU
PROST