HyGAnno: hybrid graph neural network–based cell type annotation for single-cell ATAC sequencing data
Ontology highlight
ABSTRACT:
SUBMITTER:
PROVIDER: S-EPMC10998639 | biostudies-literature | 2024 Apr
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:MotivationSingle-cell analysis offers insights into cellular heterogeneity and individual cell function. Cell type annotation is the first and critical step for performing such an analysis. Current methods mostly utilize single-cell RNA sequencing data. Several studies demonstrated improved unsupervised annotation when combining RNA with single-cell ATAC sequencing, but improvements in supervised methods have not been explored.ResultsSingle-cell 10x genomics multiome datasets containing paired ATAC and RNA from human peripheral blood mononuclear cells (PBMC) and neuronal cells with Alzheimer's Disease were used for supervised annotation. Using linear and nonlinear dimensionality reduction methods and random forest, support vector machine and logistic regression classification models, we demonstrate the improvement in supervised annotation and prediction confidence in PBMC data when using a combination of RNA seq and ATAC-seq data. No such improvement was observed when annotating neuronal cells. Specifically, F1 scores were improved when using scVI embeddings to annotate PBMC sub-types. CD4 T effector memory cells showed the largest improvement in F1 score.
| S-EPMC11863512 | biostudies-literature
Project description:Cell type annotation is a critical step in analyzing single-cell RNA sequencing (scRNA-seq) data. A large number of deep learning (DL)-based methods have been proposed to annotate cell types of scRNA-seq data and have achieved impressive results. However, there are several limitations to these methods. First, they do not fully exploit cell-to-cell differential features. Second, they are developed based on shallow features and lack of flexibility in integrating high-order features in the data. Finally, the low-dimensional gene features may lead to overfitting in neural networks. To overcome those limitations, we propose a novel DL-based model, cell type annotation of single-cell RNA-seq data using residual graph convolutional neural network with contrastive learning (scRGCL), based on residual graph convolutional neural network and contrastive learning for cell type annotation of single-cell RNA-seq data. scRGCL mainly consists of a residual graph convolutional neural network, contrastive learning, and weight freezing. A residual graph convolutional neural network is utilized to extract complex high-order features from data. Contrastive learning can help the model learn meaningful cell-to-cell differential features. Weight freezing can avoid overfitting and help the model discover the impact of specific gene expression on cell type annotation. To verify the effectiveness of scRGCL, we compared its performance with six methods (three shallow learning algorithms and three state-of-the-art DL-based methods) on eight single-cell benchmark datasets from two species (seven in human and one in mouse). Experimental results not only show that scRGCL outperforms competing methods but also demonstrate the generalizability of scRGCL for cell type annotation. scRGCL is available at https://github.com/nathanyl/scRGCL.
| S-EPMC11663015 | biostudies-literature
Project description:As single-cell chromatin accessibility profiling methods advance, scATAC-seq has become ever more important in the study of candidate regulatory genomic regions and their roles underlying developmental, evolutionary, and disease processes. At the same time, cell type annotation is critical in understanding the cellular composition of complex tissues and identifying potential novel cell types. However, most existing methods that can perform automated cell type annotation are designed to transfer labels from an annotated scRNA-seq data set to another scRNA-seq data set, and it is not clear whether these methods are adaptable to annotate scATAC-seq data. Several methods have been recently proposed for label transfer from scRNA-seq data to scATAC-seq data, but there is a lack of benchmarking study on the performance of these methods. Here, we evaluated the performance of five scATAC-seq annotation methods on both their classification accuracy and scalability using publicly available single-cell datasets from mouse and human tissues including brain, lung, kidney, PBMC, and BMMC. Using the BMMC data as basis, we further investigated the performance of these methods across different data sizes, mislabeling rates, sequencing depths and the number of cell types unique to scATAC-seq. Bridge integration, which is the only method that requires additional multimodal data and does not need gene activity calculation, was overall the best method and robust to changes in data size, mislabeling rate and sequencing depth. Conos was the most time and memory efficient method but performed the worst in terms of prediction accuracy. scJoint tended to assign cells to similar cell types and performed relatively poorly for complex datasets with deep annotations but performed better for datasets only with major label annotations. The performance of scGCN and Seurat v3 was moderate, but scGCN was the most time-consuming method and had the most similar performance to random classifiers for cell types unique to scATAC-seq.
| S-EPMC9792779 | biostudies-literature
Project description:MotivationTranscription factor binding sites (TFBSs) prediction is a crucial step in revealing functions of transcription factors (TFs) from high-throughput sequencing data. Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) provides insight on TFBSs and nucleosome positioning by probing open chromatic, which can simultaneously reveal multiple TFBSs compare to traditional technologies. The existing tools based on convolutional neural network (CNN) only find the fixed length of TFBSs from ATAC-seq data. Graph neural network (GNN) can be considered as the extension of CNN, which has great potential in finding multiple TFBSs with different lengths from ATAC-seq data.ResultsWe develop a motif predictor called MMGraph based on three-layer GNN and coexisting probability of k-mers for finding multiple motifs from ATAC-seq data. The results of the experiment which has been conducted on 88 ATAC-seq datasets indicate that MMGraph has achieved the best performance on area of eight metrics radar (AEMR) score of 2.31 and could find 207 higher quality multiple motifs than other existing tools.AvailabilityMMGraph is wrapped in Python package, which is available at https://github.com/zhangsq06/MMGraph.git.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC9524997 | biostudies-literature
Project description: Not available
| S-EPMC10956247 | biostudies-literature
Project description:Automatic cell type annotation methods are increasingly used in single-cell RNA sequencing (scRNA-seq) analysis due to their fast and precise advantages. However, current methods often fail to account for the imbalance of scRNA-seq datasets and ignore information from smaller populations, leading to significant biological analysis errors. Here, we introduce scBalance, an integrated sparse neural network framework that incorporates adaptive weight sampling and dropout techniques for auto-annotation tasks. Using 20 scRNA-seq datasets with varying scales and degrees of imbalance, we demonstrate that scBalance outperforms current methods in both intra- and inter-dataset annotation tasks. Additionally, scBalance displays impressive scalability in identifying rare cell types in million-level datasets, as shown in the bronchoalveolar cell landscape. scBalance is also significantly faster than commonly used tools and comes in a user-friendly format, making it a superior tool for scRNA-seq analysis on the Python-based platform.
| S-EPMC10199434 | biostudies-literature
Project description:Advances in single-cell RNA sequencing (scRNA-seq) have furthered the simultaneous classification of thousands of cells in a single assay based on transcriptome profiling. In most analysis protocols, single-cell type annotation relies on marker genes or RNA-seq profiles, resulting in poor extrapolation. Still, the accurate cell-type annotation for single-cell transcriptomic data remains a great challenge. Here, we introduce scDeepSort (https://github.com/ZJUFanLab/scDeepSort), a pre-trained cell-type annotation tool for single-cell transcriptomics that uses a deep learning model with a weighted graph neural network (GNN). Using human and mouse scRNA-seq data resources, we demonstrate the high performance and robustness of scDeepSort in labeling 764 741 cells involving 56 human and 32 mouse tissues. Significantly, scDeepSort outperformed other known methods in annotating 76 external test datasets, reaching an 83.79% accuracy across 265 489 cells in humans and mice. Moreover, we demonstrate the universality of scDeepSort using more challenging datasets and using references from different scRNA-seq technology. Above all, scDeepSort is the first attempt to annotate cell types of scRNA-seq data with a pre-trained GNN model, which can realize the accurate cell-type annotation without additional references, i.e. markers or RNA-seq profiles.
| S-EPMC8643674 | biostudies-literature
Project description:The metabolic heterogeneity and metabolic interplay between cells are known as significant contributors to disease treatment resistance. However, with the lack of a mature high-throughput single-cell metabolomics technology, we are yet to establish systematic understanding of the intra-tissue metabolic heterogeneity and cooperative mechanisms. To mitigate this knowledge gap, we developed a novel computational method, namely, single-cell flux estimation analysis (scFEA), to infer the cell-wise fluxome from single-cell RNA-sequencing (scRNA-seq) data. scFEA is empowered by a systematically reconstructed human metabolic map as a factor graph, a novel probabilistic model to leverage the flux balance constraints on scRNA-seq data, and a novel graph neural network-based optimization solver. The intricate information cascade from transcriptome to metabolome was captured using multilayer neural networks to capitulate the nonlinear dependency between enzymatic gene expressions and reaction rates. We experimentally validated scFEA by generating an scRNA-seq data set with matched metabolomics data on cells of perturbed oxygen and genetic conditions. Application of scFEA on this data set showed the consistency between predicted flux and the observed variation of metabolite abundance in the matched metabolomics data. We also applied scFEA on five publicly available scRNA-seq and spatial transcriptomics data sets and identified context- and cell group-specific metabolic variations. The cell-wise fluxome predicted by scFEA empowers a series of downstream analyses including identification of metabolic modules or cell groups that share common metabolic variations, sensitivity evaluation of enzymes with regards to their impact on the whole metabolic flux, and inference of cell-tissue and cell-cell metabolic communications.
| S-EPMC8494226 | biostudies-literature
Project description:Cross-species comparative analyses of single-cell RNA sequencing (scRNA-seq) data allow us to explore, at single-cell resolution, the origins of the cellular diversity and evolutionary mechanisms that shape cellular form and function. Cell-type assignment is a crucial step to achieve that. However, the poorly annotated genome and limited known biomarkers hinder us from assigning cell identities for nonmodel species. Here, we design a heterogeneous graph neural network model, CAME, to learn aligned and interpretable cell and gene embeddings for cross-species cell-type assignment and gene module extraction from scRNA-seq data. CAME achieves significant improvements in cell-type characterization across distant species owing to the utilization of non-one-to-one homologous gene mapping ignored by early methods. Our large-scale benchmarking study shows that CAME significantly outperforms five classical methods in terms of cell-type assignment and model robustness to insufficiency and inconsistency of sequencing depths. CAME can transfer the major cell types and interneuron subtypes of human brains to mouse and discover shared cell-type-specific functions in homologous gene modules. CAME can align the trajectories of human and macaque spermatogenesis and reveal their conservative expression dynamics. In short, CAME can make accurate cross-species cell-type assignments even for nonmodel species and uncover shared and divergent characteristics between two species from scRNA-seq data.
| S-EPMC9977153 | biostudies-literature
Project description:MotivationSingle-cell RNA sequencing (scRNA-seq) data, annotated by cell type, is useful in a variety of downstream biological applications, such as profiling gene expression at the single-cell level. However, manually assigning these annotations with known marker genes is both time-consuming and subjective.ResultsWe present a Graph Convolutional Network (GCN)-based approach to automate the annotation process. Our process builds upon existing labeling approaches, using state-of-the-art tools to find cells with highly confident label assignments through consensus and spreading these confident labels with a semi-supervised GCN. Using simulated data and two scRNA-seq datasets from different tissues, we show that our method improves accuracy over a simple consensus algorithm and the average of the underlying tools. We also compare our method to a nonparametric neighbor majority approach, showing comparable results. We then demonstrate that our GCN method allows for feature interpretation, identifying important genes for cell type classification. We present our completed pipeline, written in PyTorch, as an end-to-end tool for automating and interpreting the classification of scRNA-seq data.Availability and implementationOur code for conducting the experiments in this paper and using our model is available at https://github.com/lewinsohndp/scSHARP.
| S-EPMC10272704 | biostudies-literature