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1.
Brief Bioinform ; 24(5)2023 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-37466210

RESUMO

MOTIVATION: Recent advances in spatial transcriptomics technologies have enabled gene expression profiles while preserving spatial context. Accurately identifying spatial domains is crucial for downstream analysis and it requires the effective integration of gene expression profiles and spatial information. While increasingly computational methods have been developed for spatial domain detection, most of them cannot adaptively learn the complex relationship between gene expression and spatial information, leading to sub-optimal performance. RESULTS: To overcome these challenges, we propose a novel deep learning method named Spatial-MGCN for identifying spatial domains, which is a Multi-view Graph Convolutional Network (GCN) with attention mechanism. We first construct two neighbor graphs using gene expression profiles and spatial information, respectively. Then, a multi-view GCN encoder is designed to extract unique embeddings from both the feature and spatial graphs, as well as their shared embeddings by combining both graphs. Finally, a zero-inflated negative binomial decoder is used to reconstruct the original expression matrix by capturing the global probability distribution of gene expression profiles. Moreover, Spatial-MGCN incorporates a spatial regularization constraint into the features learning to preserve spatial neighbor information in an end-to-end manner. The experimental results show that Spatial-MGCN outperforms state-of-the-art methods consistently in several tasks, including spatial clustering and trajectory inference.


Assuntos
Oftalmopatias Hereditárias , Doenças Genéticas Ligadas ao Cromossomo X , Humanos , Perfilação da Expressão Gênica
2.
Bioinformatics ; 39(3)2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36825817

RESUMO

MOTIVATION: Single-cell RNA-sequencing (scRNA-seq) is widely used to reveal cellular heterogeneity, complex disease mechanisms and cell differentiation processes. Due to high sparsity and complex gene expression patterns, scRNA-seq data present a large number of dropout events, affecting downstream tasks such as cell clustering and pseudo-time analysis. Restoring the expression levels of genes is essential for reducing technical noise and facilitating downstream analysis. However, existing scRNA-seq data imputation methods ignore the topological structure information of scRNA-seq data and cannot comprehensively utilize the relationships between cells. RESULTS: Here, we propose a single-cell Graph Contrastive Learning method for scRNA-seq data imputation, named scGCL, which integrates graph contrastive learning and Zero-inflated Negative Binomial (ZINB) distribution to estimate dropout values. scGCL summarizes global and local semantic information through contrastive learning and selects positive samples to enhance the representation of target nodes. To capture the global probability distribution, scGCL introduces an autoencoder based on the ZINB distribution, which reconstructs the scRNA-seq data based on the prior distribution. Through extensive experiments, we verify that scGCL outperforms existing state-of-the-art imputation methods in clustering performance and gene imputation on 14 scRNA-seq datasets. Further, we find that scGCL can enhance the expression patterns of specific genes in Alzheimer's disease datasets. AVAILABILITY AND IMPLEMENTATION: The code and data of scGCL are available on Github: https://github.com/zehaoxiong123/scGCL. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Perfilação da Expressão Gênica , Software , Análise de Sequência de RNA , Análise da Expressão Gênica de Célula Única , Análise de Célula Única/métodos , Análise por Conglomerados
3.
Bioinformatics ; 38(22): 5042-5048, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36193998

RESUMO

MOTIVATION: Cell-type annotation plays a crucial role in single-cell RNA-seq (scRNA-seq) data analysis. As more and more well-annotated scRNA-seq reference data are publicly available, automatical label transference algorithms are gaining popularity over manual marker gene-based annotation methods. However, most existing methods fail to unify cell-type annotation with dimensionality reduction and are unable to generate deep latent representation from the perspective of data generation. RESULTS: In this article, we propose scSemiGAN, a single-cell semi-supervised cell-type annotation and dimensionality reduction framework based on a generative adversarial network, to overcome these challenges, modeling scRNA-seq data from the aspect of data generation. Our proposed scSemiGAN is capable of performing deep latent representation learning and cell-type label prediction simultaneously. Through extensive comparison with four state-of-the-art annotation methods on diverse simulated and real scRNA-seq datasets, scSemiGAN achieves competitive or superior performance in multiple downstream tasks including cell-type annotation, latent representation visualization, confounding factor removal and enrichment analysis. AVAILABILITY AND IMPLEMENTATION: The code and data of scSemiGAN are available on GitHub: https://github.com/rafa-nadal/scSemiGAN. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Algoritmos , Análise de Célula Única , Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos , Análise de Dados , Sequenciamento do Exoma , Perfilação da Expressão Gênica/métodos
4.
Int J Biol Macromol ; 215: 262-271, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-35671909

RESUMO

Drought stress has been the main abiotic factor affecting the growth, development and production of common buckwheat (Fagopyrum esculentum). To explore the response mechanisms of regulating buckwheat drought stress on the post-transcriptional and translational levels, a comparative proteomic analysis was applied to monitor the short-term proteomic variations under the drought stress in the seedling stage. From which 593 differentially abundant proteins (DAPs) were identified using the TMT-based proteomics analysis. A number of DAPs were found to be intimately correlated with the styrene degradation, phenylpropanoid biosynthesis and stimulus response, within which. The acyl-CoA oxidase 4 (ACX4), a key regulator in plant abiotic stress response, was selected for further elucidation. Overexpression of the FeACX4 not only conferred drought and salt tolerance in the Arabidopsis, but also significantly increased the root length and fresh weight in the overexpression lines plant relative to the wild type (WT) plant, accompanied by the elevated activities of catalase (CAT) and lowered malonaldehyde (MDA) and H2O2 contents, therefore allowing plants to better adapt to adverse environments. Our results provided information in the exploring of the molecular regulation mechanism responding to drought tolerance in common buckwheat.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Fagopyrum , Acil-CoA Oxidase/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Secas , Fagopyrum/genética , Fagopyrum/metabolismo , Regulação da Expressão Gênica de Plantas , Peróxido de Hidrogênio/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Proteômica , Estresse Fisiológico
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