Guohua Wang

Feb 16, 2025 | nature.com | Yi Fan |Zhuohan Yu |Yanchi Su |Haoran Zhu |Fuzhou Wang |Xingjian Chen | +5 more

Single-cell ATAC-seq technology advances our understanding of single-cell heterogeneity in gene regulation by enabling exploration of epigenetic landscapes and regulatory elements. However, low sequencing depth per cell leads to data sparsity and high dimensionality, limiting the characterization of gene regulatory elements. Here, we develop scAGDE, a single-cell chromatin accessibility model-based deep graph representation learning method that simultaneously learns representation and clustering through explicit modeling of data generation. Our evaluations demonstrated that scAGDE outperforms existing methods in cell segregation, key marker identification, and visualization across diverse datasets while mitigating dropout events and unveiling hidden chromatin-accessible regions. We find that scAGDE preferentially identifies enhancer-like regions and elucidates complex regulatory landscapes, pinpointing putative enhancers regulating the constitutive expression of CTLA4 and the transcriptional dynamics of CD8A in immune cells. When applied to human brain tissue, scAGDE successfully annotated cis-regulatory element-specified cell types and revealed functional diversity and regulatory mechanisms of glutamatergic neurons. Single-cell ATAC-seq reveals gene regulation at individual cell levels but struggles with data sparsity. Here, authors introduce scAGDE, a deep graph learning framework that improves cell embedding and clustering, outperforming existing methods and uncovering key regulatory mechanisms.

Dec 13, 2024 | mdpi.com | Guohua Wang

1. IntroductionAs a gathering place of resources (including more employment opportunities, better medical and educational environment, and more convenient living and transportation conditions), cities attract a large population to settle down. Urban space is gathering more and more resources and population in the process of urbanization, from the spatial expansion in the early stage to the shrewd contraction later, making the living environment increasingly crowded [1].

Nov 19, 2023 | nature.com | Guohua Wang

AbstractHypobaric hypoxia (HH) exposure affects appetite and serum iron levels in both humans and animals. Thus, whether appetite-regulating ghrelin is involved in iron regulation under HH needs to be elucidated. In vivo, C57BL/6J mice were placed in a hypobaric chamber to establish a 6000-m-high altitude exposure animal model. In vitro, mouse primary hepatocytes and peritoneal macrophages were exposed to hypoxia (1% O2) to examine the effects of ghrelin on iron-regulating proteins.

Oct 19, 2023 | nature.com | Jiangning Song |Robin B Gasser |Ruedi Aebersold |Guohua Wang

AbstractCell type deconvolution is a computational method for the determination/resolution of cell type proportions from bulk sequencing data, and is frequently used for the analysis of divergent cell types in tumour tissue samples. However, deconvolution technology is still in its infancy for the analysis of cell types using proteomic data due to challenges with repeatability/reproducibility, variable reference standards and the lack of single-cell proteomic reference data.

Jun 25, 2023 | biorxiv.org | Kevin Emmerich |Steven Walker |Guohua Wang |David White

AbstractRetinal Muller glia (MG) can act as stem-like cells to generate new neurons in both zebrafish and mice. In zebrafish, retinal regeneration is innate and robust, resulting in the replacement of lost neurons and restoration of visual function. In mice, exogenous stimulation of MG is required to reveal a dormant and, to date, limited regenerative capacity. Zebrafish studies have been key in revealing factors that promote regenerative responses in the mammalian eye.