SpatialcoGCN: deconvolution and spatial information–aware simulation of spatial transcriptomics data via deep graph co-embedding
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PROVIDER: S-EPMC10982953 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
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Project description:Spatial transcriptomics (ST) technologies have emerged as an effective tool to identify the spatial architecture of tissues, facilitating a comprehensive understanding of organ function and the tissue microenvironment. Spatial domain identification is the first and most critical step in ST data analysis, which requires thoughtful utilization of tissue microenvironment and morphological priors. Here, we propose a graph contrastive learning framework, GRAS4T, which combines contrastive learning and a subspace analysis model to accurately distinguish different spatial domains by capturing the tissue microenvironment through self-expressiveness of spots within the same domain. To uncover the pertinent features for spatial domain identification, GRAS4T employs a graph augmentation based on histological image priors, preserving structural information crucial for the clustering task. Experimental results on eight ST datasets from five different platforms show that GRAS4T outperforms five state-of-the-art competing methods. Significantly, GRAS4T excels at separating distinct tissue structures and unveiling more detailed spatial domains. GRAS4T combines the advantages of subspace analysis and graph representation learning with extensibility, making it an ideal framework for ST domain identification.
| S-EPMC11539238 | biostudies-literature
Project description:Deciphering the cellular abundance in spatial transcriptomics (ST) is crucial for revealing the spatial architecture of cellular heterogeneity within tissues. However, some of the current spatial sequencing technologies are in low resolutions, leading to each spot having multiple heterogeneous cells. Additionally, current spatial deconvolution methods lack the ability to utilize multi-modality information such as gene expression and chromatin accessibility from single-cell multi-omics data. In this study, we introduce a graph Contrastive Learning and Partial Least Squares regression-based method, CLPLS, to deconvolute ST data. CLPLS is a flexible method that it can be extended to integrate ST data and single-cell multi-omics data, enabling the exploration of the spatially epigenomic heterogeneity. We applied CLPLS to both simulated and real datasets coming from different platforms. Benchmark analyses with other methods on these datasets show the superior performance of CLPLS in deconvoluting spots in single cell level.
| S-EPMC11807730 | biostudies-literature
Project description:MotivationUnveiling the heterogeneity in the tissues is crucial to explore cell-cell interactions and cellular targets of human diseases. Spatial transcriptomics (ST) supplies spatial gene expression profile which has revolutionized our biological understanding, but variations in cell-type proportions of each spot with dozens of cells would confound downstream analysis. Therefore, deconvolution of ST has been an indispensable step and a technical challenge toward the higher-resolution panorama of tissues.ResultsHere, we propose a novel ST deconvolution method called SD2 integrating spatial information of ST data and embracing an important characteristic, dropout, which is traditionally considered as an obstruction in single-cell RNA sequencing data (scRNA-seq) analysis. First, we extract the dropout-based genes as informative features from ST and scRNA-seq data by fitting a Michaelis-Menten function. After synthesizing pseudo-ST spots by randomly composing cells from scRNA-seq data, auto-encoder is applied to discover low-dimensional and non-linear representation of the real- and pseudo-ST spots. Next, we create a graph containing embedded profiles as nodes, and edges determined by transcriptional similarity and spatial relationship. Given the graph, a graph convolutional neural network is used to predict the cell-type compositions for real-ST spots. We benchmark the performance of SD2 on the simulated seqFISH+ dataset with different resolutions and measurements which show superior performance compared with the state-of-the-art methods. SD2 is further validated on three real-world datasets with different ST technologies and demonstrates the capability to localize cell-type composition accurately with quantitative evidence. Finally, ablation study is conducted to verify the contribution of different modules proposed in SD2.Availability and implementationThe SD2 is freely available in github (https://github.com/leihouyeung/SD2) and Zenodo (https://doi.org/10.5281/zenodo.7024684).Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC9789790 | biostudies-literature
Project description:Deep simulations have gained widespread attention owing to their excellent acceleration performances. However, these methods cannot provide effective collision detection and response strategies. We propose a deep interactive physical simulation framework that can effectively address tool-object collisions. The framework can predict the dynamic information by considering the collision state. In particular, the graph neural network is chosen as the base model, and a collision-aware recursive regression module is introduced to update the network parameters recursively using interpenetration distances calculated from the vertex-face and edge-edge tests. Additionally, a novel self-supervised collision term is introduced to provide a more compact collision response. This study extensively evaluates the proposed method and shows that it effectively reduces interpenetration artifacts while ensuring high simulation efficiency.
| S-EPMC9170855 | biostudies-literature
Project description:Spatial transcriptomics are a collection of genomic technologies that have enabled transcriptomic profiling on tissues with spatial localization information. Analyzing spatial transcriptomic data is computationally challenging, as the data collected from various spatial transcriptomic technologies are often noisy and display substantial spatial correlation across tissue locations. Here, we develop a spatially-aware dimension reduction method, SpatialPCA, that can extract a low dimensional representation of the spatial transcriptomics data with biological signal and preserved spatial correlation structure, thus unlocking many existing computational tools previously developed in single-cell RNAseq studies for tailored analysis of spatial transcriptomics. We illustrate the benefits of SpatialPCA for spatial domain detection and explores its utility for trajectory inference on the tissue and for high-resolution spatial map construction. In the real data applications, SpatialPCA identifies key molecular and immunological signatures in a detected tumor surrounding microenvironment, including a tertiary lymphoid structure that shapes the gradual transcriptomic transition during tumorigenesis and metastasis. In addition, SpatialPCA detects the past neuronal developmental history that underlies the current transcriptomic landscape across tissue locations in the cortex.
| S-EPMC9684472 | biostudies-literature
Project description:BackgroundRecent advancements in spatially resolved transcriptomics (SRT) have opened up unprecedented opportunities to explore gene expression patterns within spatial contexts. Deciphering spatial domains is a critical task in spatial transcriptomic data analysis, aiding in the elucidation of tissue structural heterogeneity and biological functions. However, existing spatial domain detection methods ignore the consistency of expression patterns and spatial arrangements between spots, as well as the severe gene dropout phenomenon present in SRT data, resulting in suboptimal performance in identifying tissue spatial heterogeneity.ResultsIn this paper, we introduce a novel framework, spatially regularized deep graph networks (SR-DGN), which integrates gene expression profiles with spatial information to learn spatially-consistent and informative spot representations. Specifically, SR-DGN employs graph attention networks (GAT) to adaptively aggregate gene expression information from neighboring spots, considering local expression patterns between spots. In addition, the spatial regularization constraint ensures the consistency of neighborhood relationships between physical and embedded spaces in an end-to-end manner. SR-DGN also employs cross-entropy (CE) loss to model gene expression states, effectively mitigating the impact of noisy gene dropouts.ConclusionsExperimental results demonstrate that SR-DGN outperforms state-of-the-art methods in spatial domain identification across SRT data from different sequencing platforms. Moreover, SR-DGN is capable of recovering known microanatomical structures, yielding clearer low-dimensional visualizations and more accurate spatial trajectory inferences.
| S-EPMC11607964 | biostudies-literature
Project description: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.
| S-EPMC9464662 | biostudies-literature
Project description:The microbiome-wide association studies are to figure out the relationship between microorganisms and humans, with the goal of discovering relevant biomarkers to guide disease diagnosis. However, the microbiome data is complex, with high noise and dimensions. Traditional machine learning methods are limited by the models' representation ability and cannot learn complex patterns from the data. Recently, deep learning has been widely applied to fields ranging from text processing to image recognition due to its efficient flexibility and high capacity. But the deep learning models must be trained with enough data in order to achieve good performance, which is impractical in reality. In addition, deep learning is considered as black box and hard to interpret. These factors make deep learning not widely used in microbiome-wide association studies. In this work, we construct a sparse microbial interaction network and embed this graph into deep model to alleviate the risk of overfitting and improve the performance. Further, we explore a Graph Embedding Deep Feedforward Network (GEDFN) to conduct feature selection and guide meaningful microbial markers' identification. Based on the experimental results, we verify the feasibility of combining the microbial graph model with the deep learning model, and demonstrate the feasibility of applying deep learning and feature selection on microbial data. Our main contributions are: firstly, we utilize different methods to construct a variety of microbial interaction networks and combine the network via graph embedding deep learning. Secondly, we introduce a feature selection method based on graph embedding and validate the biological meaning of microbial markers. The code is available at https://github.com/MicroAVA/GEDFN.git.
| S-EPMC6883002 | biostudies-literature
Project description:Spatially resolved transcriptomics performs high-throughput measurement of transcriptomes while preserving spatial information about the cellular organizations. However, many spatially resolved transcriptomic technologies can only distinguish spots consisting of a mixture of cells instead of working at single-cell resolution. Here, we present STdGCN, a graph neural network model designed for cell type deconvolution of spatial transcriptomic (ST) data that can leverage abundant single-cell RNA sequencing (scRNA-seq) data as reference. STdGCN is the first model incorporating the expression profiles from single cell data as well as the spatial localization information from the ST data for cell type deconvolution. Extensive benchmarking experiments on multiple ST datasets showed that STdGCN outperformed 14 published state-of-the-art models. Applied to a human breast cancer Visium dataset, STdGCN discerned spatial distributions between stroma, lymphocytes and cancer cells for tumor microenvironment dissection. In a human heart ST dataset, STdGCN detected the changes of potential endothelial-cardiomyocyte communications during tissue development.
| S-EPMC10274700 | biostudies-literature
Project description:Graph embedding has gained significant popularity due to its ability to represent large-scale graph data by mapping nodes to a low-dimensional space. However, most of the existing research in this field has focused on transductive learning, where fixed node embeddings are generated by training the entire graph. This approach is not well-suited for temporal graphs that undergo continuous changes with the addition of new nodes and interactions. To address this limitation, we propose an inductive temporal graph embedding method called MIAN (Multi-angle Information Aggregation Network). The key focus of MIAN is to design an aggregation function that combines multi-angle information for generating node embeddings. Specifically, we divide the information into different angles, including neighborhood, temporal, and environment. Each angle of information is modeled and mined independently, and then fed into an improved gated recuttent unit (GRU) module to effectively combine them. To assess the performance of MIAN, we conduct extensive experiments on various real-world datasets and compare its results with several state-of-the-art baseline methods across diverse tasks. The experimental findings demonstrate that MIAN outperforms these methods.
| S-EPMC11623124 | biostudies-literature