De novo analysis of bulk RNA-seq data at spatially resolved single-cell resolution

Liao, Jie; Qian, Jingyang; Yin, Fang; Chen, Zhuo; Zhuang, Xiang; Zhang, Ningyu; Shao, Xin; Hu, Yining; Yang, Penghui; Cheng, Jiajing; Hu, Yang; Yu, Lingqi; Yang, Hua; Zhang, Jinlu; Lu, Xiaoyan; Li, Shao; Wu, Dan; Gao, Yue; Chen, Huajun; Fan, Xiaohui

doi:10.1038/s41467-022-34271-z

Cited by 39 publications

(32 citation statements)

References 72 publications

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“…β galactosidase staining, which is widely used as a marker of cellular senescence in vivo and in vitro, was not different at baseline, over time, or between genotypes, making this particular mechanism less likely to explain the PDB-like lesions in our Grk3 -deficient mice. The authors acknowledge limitations of bulk RNAseq data in that having to pre-select certain cell types for homogeneity may narrow the analysis such that other molecular pathways are missed [ 46 ]. It is possible that the subpopulation of osteoclasts that are abnormal in the Grk3 − / − mouse does not originate from this bone marrow population, as osteoclasts have several precursor cells [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Aged G Protein-Coupled Receptor Kinase 3 (Grk3)-Deficient Mice Exhibit Enhanced Osteoclastogenesis and Develop Bone Lesions Analogous to Human Paget’s Disease of Bone

Rabjohns

Rampersad

Ghosh

et al. 2023

Cells

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Paget’s Disease of Bone (PDB) is a metabolic bone disease that is characterized by dysregulated osteoclast function leading to focal abnormalities of bone remodeling. It can lead to pain, fracture, and bone deformity. G protein-coupled receptor kinase 3 (GRK3) is an important negative regulator of G protein-coupled receptor (GPCR) signaling. GRK3 is known to regulate GPCR function in osteoblasts and preosteoblasts, but its regulatory function in osteoclasts is not well defined. Here, we report that Grk3 expression increases during osteoclast differentiation in both human and mouse primary cells and established cell lines. We also show that aged mice deficient in Grk3 develop bone lesions similar to those seen in human PDB and other Paget’s Disease mouse models. We show that a deficiency in Grk3 expression enhances osteoclastogenesis in vitro and proliferation of hematopoietic osteoclast precursors in vivo but does not affect the osteoclast-mediated bone resorption function or cellular senescence pathway. Notably, we also observe decreased Grk3 expression in peripheral blood mononuclear cells of patients with PDB compared with age- and gender-matched healthy controls. Our data suggest that GRK3 has relevance to the regulation of osteoclast differentiation and that it may have relevance to the pathogenesis of PDB and other metabolic bone diseases associated with osteoclast activation.

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Section: Discussionmentioning

confidence: 99%

Aged G Protein-Coupled Receptor Kinase 3 (Grk3)-Deficient Mice Exhibit Enhanced Osteoclastogenesis and Develop Bone Lesions Analogous to Human Paget’s Disease of Bone

Rabjohns

Rampersad

Ghosh

et al. 2023

Cells

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“…(𝑥|𝑣, 𝑤) = 𝑆(𝑣, 𝑤) , where 𝜃 represents the generative model parameters. We aim to develop an unsupervised deep generative model that, using only the samples of 𝑋, learns the joint distribution of the data x and a set of latent variables z (𝑧 ∈ ℝ 7 , where 𝑀 ≥ 𝐾) for generating observed data x, i.e., 𝑝 ! (𝑥|𝑧) ≈ 𝑝(𝑥|𝑣, 𝑤) = 𝑆(𝑣, 𝑤).…”

Section: Methods For Bulktrajblendmentioning

confidence: 99%

OmicVerse: A single pipeline for exploring the entire transcriptome universe

Zeng¹,

Ma²,

Hu³

et al. 2023

Preprint

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Single-cell sequencing often results in cellular "interruptions" due to limitations in sequencing throughput, while bulk RNA-seq may contain these potential "interrupted" cells. Here, we propose the BulkTrajBlend algorithm in OmicVerse that combines Beta-Variational AutoEncoder for deconvolution and graph neural networks for overlapping community discovery to effectively interpolate and restore the continuity of "interrupted" cells in the original scRNA-seq data. Additionally, OmicVerse serves as a comprehensive tool, providing standardized and consistent access to a wide range of methods for bulk and single cell RNA-seq analysis, enhancing computational efficiency and enabling beautiful visualization, and helping researchers to explore the transcriptomic universe, unravel novel biological insights, and propel scientific discoveries.

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“…Bulk2Space is available as a python package and the source code is deposited at the GitHub (https://github.com/ZJUFanLab/bulk2space) 75 . b, Gene expression correlation and gene expression variation of three methods with unpaired simulation data (n=12).…”

Section: Code Availabilitymentioning

confidence: 99%

“…Bulk2Space is available as a python package and the source code is deposited at the GitHub (https://github.com/ZJUFanLab/bulk2space) 75 .…”

Section: Code Availabilitymentioning

confidence: 99%

De novoanalysis of bulk RNA-seq data at spatially resolved single-cell resolution

Liao

Qian

Yin

et al. 2022

Preprint

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Uncovering the tissue molecular architecture at single-cell resolution could help better understand the biological and pathological processes in organisms. However, bulk RNA-seq can only measure gene expression in cell mixtures, without revealing molecular heterogeneity and spatial patterns of single cells. Herein, we introduce Bulk2Space (https://github.com/ZJUFanLab/bulk2space), a deep learning framework-based spatial deconvolution algorithm that can simultaneously reveal the spatial and cellular heterogeneity of bulk RNA-seq data. The use of bulk transcriptomics to validate Bulk2Space revealed, in particular, the spatial variance of immune cells in different tumor regions, the molecular and spatial heterogeneity of tissues during inflammation-induced tumorigenesis, and spatial patterns of novel genes in different cell types. Moreover, Bulk2Space further annotated cell types that cannot be identified by original methods when it was used to spatially deconvolve the bulk data derived from our in-house developed sequencing approach Spatial-seq. Bulk2Space is distributed via an open-source Python software package.

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De novo analysis of bulk RNA-seq data at spatially resolved single-cell resolution

Cited by 39 publications

References 72 publications

Aged G Protein-Coupled Receptor Kinase 3 (Grk3)-Deficient Mice Exhibit Enhanced Osteoclastogenesis and Develop Bone Lesions Analogous to Human Paget’s Disease of Bone

Aged G Protein-Coupled Receptor Kinase 3 (Grk3)-Deficient Mice Exhibit Enhanced Osteoclastogenesis and Develop Bone Lesions Analogous to Human Paget’s Disease of Bone

OmicVerse: A single pipeline for exploring the entire transcriptome universe

De novoanalysis of bulk RNA-seq data at spatially resolved single-cell resolution

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