scholarly journals GCNG: Graph convolutional networks for inferring cell-cell interactions

Author(s):  
Ye Yuan ◽  
Ziv Bar-Joseph

AbstractSeveral methods have been developed for inferring gene-gene interactions from expression data. To date, these methods mainly focused on intra-cellular interactions. The availability of high throughput spatial expression data opens the door to methods that can infer such interactions both within and between cells. However, the spatial data also raises several new challenges. These include issues related to the sparse, noisy expression vectors for each cell, the fact that several different cell types are often profiled, the definition of a neighborhood of cell and the relatively small number of extracellular interactions. To enable the identification of gene interactions between cells we extended a Graph Convolutional Neural network approach for Genes (GCNG). We encode the spatial information as a graph and use the network to combine it with the expression data using supervised training. Testing GCNG on spatial transcriptomics data we show that it improves upon prior methods suggested for this task and can propose novel pairs of extracellular interacting genes. Finally, we show that the output of GCNG can also be used for down-stream analysis including functional assignment.Supporting website with software and data: https://github.com/xiaoyeye/GCNG.

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Ye Yuan ◽  
Ziv Bar-Joseph

AbstractMost methods for inferring gene-gene interactions from expression data focus on intracellular interactions. The availability of high-throughput spatial expression data opens the door to methods that can infer such interactions both within and between cells. To achieve this, we developed Graph Convolutional Neural networks for Genes (GCNG). GCNG encodes the spatial information as a graph and combines it with expression data using supervised training. GCNG improves upon prior methods used to analyze spatial transcriptomics data and can propose novel pairs of extracellular interacting genes. The output of GCNG can also be used for downstream analysis including functional gene assignment.Supporting website with software and data: https://github.com/xiaoyeye/GCNG.


2020 ◽  
Author(s):  
Jing Su ◽  
Qianqian Song

AbstractRecent development of spatial transcriptomics (ST) is capable of associating spatial information at different spots in the tissue section with RNA abundance of cells within each spot, which is particularly important to understand tissue cytoarchitectures and functions. However, for such ST data, since a spot is usually larger than an individual cell, gene expressions measured at each spot are from a mixture of cells with heterogenous cell types. Therefore, ST data at each spot needs to be disentangled so as to reveal the cell compositions at that spatial spot. In this study, we propose a novel method, named DSTG, to accurately deconvolute the observed gene expressions at each spot and recover its cell constitutions, thus achieve high-level segmentation and reveal spatial architecture of cellular heterogeneity within tissues. DSTG not only demonstrates superior performance on synthetic spatial data generated from different protocols, but also effectively identifies spatial compositions of cells in mouse cortex layer, hippocampus slice, and pancreatic tumor tissues. In conclusion, DSTG accurately uncovers the cell states and subpopulations based on spatial localization.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alma Andersson ◽  
Ludvig Larsson ◽  
Linnea Stenbeck ◽  
Fredrik Salmén ◽  
Anna Ehinger ◽  
...  

AbstractIn the past decades, transcriptomic studies have revolutionized cancer treatment and diagnosis. However, tumor sequencing strategies typically result in loss of spatial information, critical to understand cell interactions and their functional relevance. To address this, we investigate spatial gene expression in HER2-positive breast tumors using Spatial Transcriptomics technology. We show that expression-based clustering enables data-driven tumor annotation and assessment of intra- and interpatient heterogeneity; from which we discover shared gene signatures for immune and tumor processes. By integration with single cell data, we spatially map tumor-associated cell types to find tertiary lymphoid-like structures, and a type I interferon response overlapping with regions of T-cell and macrophage subset colocalization. We construct a predictive model to infer presence of tertiary lymphoid-like structures, applicable across tissue types and technical platforms. Taken together, we combine different data modalities to define a high resolution map of cellular interactions in tumors and provide tools generalizing across tissues and diseases.


2020 ◽  
Author(s):  
Livnat Jerby-Arnon ◽  
Aviv Regev

ABSTRACTTissue homeostasis relies on orchestrated multicellular circuits, where interactions between different cell types dynamically balance tissue function. While single-cell genomics identifies tissues’ cellular components, deciphering their coordinated action remains a major challenge. Here, we tackle this problem through a new framework of multicellular programs: combinations of distinct cellular programs in different cell types that are coordinated together in the tissue, thus forming a higher order functional unit at the tissue, rather than only cell, level. We develop the open-access DIALOGUE algorithm to systematically uncover such multi-cellular programs not only from spatial data, but even from tissue dissociated and profiled as single cells, e.g., by single-cell RNA-Seq. Tested on spatial transcriptomes from the mouse hypothalamus, DIALOGUE recovered spatial information, predicted the properties of a cell’s environment only based on its transcriptome, and identified multicellular programs that mark animal behavior. Applied to brain samples and colon biopsies profiled by scRNA-Seq, DIALOGUE identified multicellular configurations that mark Alzheimer’s disease and ulcerative colitis (UC), including a program spanning five cell types that is predictive of response to anti-TNF therapy in UC patients and enriched for UC risk genes from GWAS, each acting in different cell types, but all cells acting in concert. Taken together, our study provides a novel conceptual and methodological framework to unravel multicellular regulation in health and disease.


2021 ◽  
Author(s):  
Jiachen Li ◽  
Siheng Chen ◽  
Xiaoyong Pan ◽  
Ye Yuan ◽  
Hong-bin Shen

Abstract Spatial transcriptomics data can provide high-throughput gene expression profiling and spatial structure of tissues simultaneously. An essential question of its initial analysis is cell clustering. However, most existing studies rely on only gene expression information and cannot utilize spatial information efficiently. Taking advantages of two recent technical development, spatial transcriptomics and graph neural network, we thus introduce CCST, Cell Clustering for Spatial Transcriptomics data with graph neural network, an unsupervised cell clustering method based on graph convolutional network to improve ab initio cell clustering and discovering of novel sub cell types based on curated cell category annotation. CCST is a general framework for dealing with various kinds of spatially resolved transcriptomics. With application to five in vitro and in vivo spatial datasets, we show that CCST outperforms other spatial cluster approaches on spatial transcriptomics datasets, and can clearly identify all four cell cycle phases from MERFISH data of cultured cells, and find novel functional sub cell types with different micro-environments from seqFISH+ data of brain, which are all validated experimentally, inspiring novel biological hypotheses about the underlying interactions among cell state, cell type and micro-environment.


2019 ◽  
Author(s):  
Mirjana Efremova ◽  
Miquel Vento-Tormo ◽  
Sarah A. Teichmann ◽  
Roser Vento-Tormo

AbstractCell-cell communication mediated by receptor-ligand complexes is crucial for coordinating diverse biological processes, such as development, differentiation and responses to infection. In order to understand 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 interactions1. Our repository 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, the procedures for inferring cell-cell communication networks from scRNA-seq data and present a practical step-by-step guide to help implement the protocol. CellPhoneDB v2.0 is a novel version of our resource that incorporates additional functionalities to allow users to introduce new interacting molecules and reduce the time and resources needed to interrogate large datasets. CellPhoneDB v2.0 is publicly available at https://github.com/Teichlab/cellphonedb and as a user-friendly web interface at http://www.cellphonedb.org/. In our protocol, we demonstrate how to reveal meaningful biological discoveries from CellPhoneDB v2.0 using published data sets.


Author(s):  
Xianwen Ren ◽  
Guojie Zhong ◽  
Qiming Zhang ◽  
Lei Zhang ◽  
Yujie Sun ◽  
...  

AbstractSingle-cell RNA sequencing (scRNA-seq) has revolutionized transcriptomic studies by providing unprecedented cellular and molecular throughputs, but spatial information of individual cells is lost during tissue dissociation. While imaging-based technologies such as in situ sequencing show great promise, technical difficulties currently limit their wide usage. Since cellular spatial organization is inherently encoded by cell identity and can be reconstructed, at least in part, by ligand-receptor interactions, here we present CSOmap, a computational strategy to infer cellular interaction from scRNA-seq. We show that CSOmap can successfully recapitulate the spatial organization of tumor microenvironments for multiple cancers and reveal molecular determinants of cellular interactions. Further, CSOmap readily simulates perturbation of genes or cell types to gain novel biological insights, especially into how immune cells interact in the tumor microenvironment. CSOmap can be widely applicable to interrogate cellular organizations based on scRNA-seq data for various tissues in diverse systems.


Author(s):  
Rafael Sanzio Araújo dos Anjos ◽  
Jose Leandro de Araujo Conceição ◽  
Jõao Emanuel ◽  
Matheus Nunes

The spatial information regarding the use of territory is one of the many strategies used to answer and to inform about what happened, what is happening and what may happen in geographic space. Therefore, the mapping of land use as a communication tool for the spatial data made significant progress in improving sources of information, especially over the last few decades, with new generation remote sensing products for data manipulation.


Author(s):  
Pankaj Dadheech ◽  
Dinesh Goyal ◽  
Sumit Srivastava ◽  
Ankit Kumar

Spatial queries frequently used in Hadoop for significant data process. However, vast and massive size of spatial information makes it difficult to process the spatial inquiries proficiently, so they utilized the Hadoop system for process Big Data. We have used Boolean Queries & Geometry Boolean Spatial Data for Query Optimization using Hadoop System. In this paper, we show a lightweight and adaptable spatial data index for big data which will process in Hadoop frameworks. Results demonstrate the proficiency and adequacy of our spatial ordering system for various spatial inquiries.


Algorithms ◽  
2021 ◽  
Vol 14 (5) ◽  
pp. 144
Author(s):  
Yuexing Han ◽  
Xiaolong Li ◽  
Bing Wang ◽  
Lu Wang

Image segmentation plays an important role in the field of image processing, helping to understand images and recognize objects. However, most existing methods are often unable to effectively explore the spatial information in 3D image segmentation, and they neglect the information from the contours and boundaries of the observed objects. In addition, shape boundaries can help to locate the positions of the observed objects, but most of the existing loss functions neglect the information from the boundaries. To overcome these shortcomings, this paper presents a new cascaded 2.5D fully convolutional networks (FCNs) learning framework to segment 3D medical images. A new boundary loss that incorporates distance, area, and boundary information is also proposed for the cascaded FCNs to learning more boundary and contour features from the 3D medical images. Moreover, an effective post-processing method is developed to further improve the segmentation accuracy. We verified the proposed method on LITS and 3DIRCADb datasets that include the liver and tumors. The experimental results show that the performance of the proposed method is better than existing methods with a Dice Per Case score of 74.5% for tumor segmentation, indicating the effectiveness of the proposed method.


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