Integrated analysis of multimodal single-cell data with structural similarity

Cao, Yingxin; Fu, Laiyi; Wu, Jie; Peng, Qinke; Nie, Qing; Zhang, Jing; Xie, Xiaohui

doi:10.1093/nar/gkac781

Cited by 54 publications

(30 citation statements)

References 52 publications

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“…This approach combines single-cell RNA sequencing and single-cell ATAC sequencing, allowing for integrated analysis of these modalities. Data was analyzed in R 22 using mainly the Seurat 23 and Signac 24 packages, with the SAILERX package 25 .…”

Section: Resultsmentioning

confidence: 99%

Ex vivoExpansion Potential of Murine Hematopoietic Stem Cells: A Rare Property Only Partially Predicted by Phenotype

Zhang

Konturek-Ciesla

Ouyang

et al. 2022

Preprint

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Hematopoietic stem cells (HSCs) reside at the apex of hematopoiesis, can maintain this function for life, and are the functional units in clinical bone marrow transplantation. The limited HSC numbers not only restricts their clinical use but also several embodiments of experimental research. Recently, a highly defined ex vivo culture system was shown to support several hundredfold expansion of functional in vivo HSC activity. Here, we further explored this system. Over a 3-week culture period, only 0.1% of initially seeded HSCs retained their original phenotype, which contained virtually all functional long-term HSC activity. Despite this low frequency, net HSC expansions were dramatic due to the overall extensive proliferation in cultures. Limited numbers of expanded HSCs allowed for long-term multilineage engraftment of unconditioned hosts, with candidate expanded HSCs rapidly returning to quiescence in this in vivo setting. The ex vivo differentiated progeny from candidate HSCs was rich in progenitor cell activity and allowed for radioprotection from even single cultured HSCs. Finally, clonal barcoding and competitive repopulation experiments demonstrated that successful HSC expansion emanated from rare HSC clones that was only partially predicted by phenotype, demonstrating the large impact of cellular heterogeneity for HSC biology.

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Section: Resultsmentioning

confidence: 99%

Ex vivoExpansion Potential of Murine Hematopoietic Stem Cells: A Rare Property Only Partially Predicted by Phenotype

Zhang

Konturek-Ciesla

Ouyang

et al. 2022

Preprint

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“…The scRNA‐Seq data were processed using the ‘Seurat’ R package, 11,12 with cells exhibiting less than 200 features being excluded. The data set was normalized and scaled employing Seurat's NormalizeData and ScaleData functions, respectively, with batch effects mitigated via canonical correlation analysis (CCA) 13 .…”

Section: Methodsmentioning

confidence: 99%

Prognostic and immunotherapeutic potential of regulatory T cell‐associated signature in ovarian cancer

Liu,

Shan,

Sun

et al. 2024

J Cellular Molecular Medi

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Tumour‐induced immunosuppressive microenvironments facilitate oncogenesis, with regulatory T cells (Tregs) serving as a crucial component. The significance of Treg‐associated genes within the context of ovarian cancer (OC) remains elucidated insufficiently. Utilizing single‐cell RNA sequencing (scRNA‐Seq) for the identification of Treg‐specific biomarkers, this investigation employed single‐sample gene set enrichment analysis (ssGSEA) for the derivation of a Treg signature score. Weighted gene co‐expression network analysis (WGCNA) facilitated the identification of Treg‐correlated genes. Machine learning algorithms were employed to determine an optimal prognostic model, subsequently exploring disparities across risk strata in terms of survival outcomes, immunological infiltration, pathway activation and responsiveness to immunotherapy. Through WGCNA, a cohort of 365 Treg‐associated genes was discerned, with 70 implicated in the prognostication of OC. A Tregs‐associated signature (TAS), synthesized from random survival forest (RSF) and Least Absolute Shrinkage and Selection Operator (LASSO) algorithms, exhibited robust predictive validity across both internal and external cohorts. Low TAS OC patients demonstrated superior survival outcomes, augmented by increased immunological cell infiltration, upregulated immune checkpoint expression, distinct pathway enrichment and differential response to immunotherapeutic interventions. The devised TAS proficiently prognosticates patient outcomes and delineates the immunological milieu within OC, offering a strategic instrument for the clinical stratification and selection of patients.

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“…We re‐analyzed the datasets using Seurat 40 (version 4.0.5) for general analysis, including quality control and clustering. For zebrafish and rat datasets, we applied filters to remove genes expressing <3 cells and cells expressing <200 genes or >5500 genes with mitochondrial mapping rates >30% or ribosomal mapping rates >20%, resulting in QC standard 3549 cells of zebrafish and 5050 cells of rats.…”

Section: Methodsmentioning

confidence: 99%

Cross‐species single‐cell landscape of vertebrate pineal gland

Zheng,

Song,

Zhou

et al. 2023

Journal of Pineal Research

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The pineal gland has evolved from a photoreceptive organ in fish to a neuroendocrine organ in mammals. This study integrated multiple daytime single‐cell RNA‐seq datasets from the pineal glands of zebrafish, rats, and monkeys, providing a detailed examination of the evolutionary transition at single‐cell resolution. We identified key factors responsible for the anatomical and functional transformation of the pineal gland. We retrieved and integrated daytime single‐cell transcriptomic datasets from the pineal glands of zebrafish, rats, and monkeys, resulting in a total of 22 431 cells after rigorous quality filtering. Comparative analysis was then conducted to elucidate the evolution of pineal cells, their photosensitivity, their role in melatonin production, and the signaling processes within the glands of these species. Our analysis identified distinct cellular compositions of the pineal gland in zebrafish, rats, and monkeys. Zebrafish photoreceptors exhibited comprehensive phototransduction gene expression, while specific genes, including transducin (Gngt1, Gnb3, and Gngt2) and phosducin (Pdc), were consistently present in mammalian pinealocytes. We found transcriptional similarities between the pineal gland and retina, underscoring shared evolutionary and functional pathways. Zebrafish displayed unique light‐responsive circadian gene activity compared to rats and monkeys. Key ligand‐receptor interactions were identified, especially involving MDK and PTN, influencing melatonin synthesis across species. Furthermore, we observed species‐specific GPCR (G protein‐coupled receptors) expressions related to melatonin synthesis and their alignment with retinal expressions. Our findings also highlighted specific transcription factors (TFs) and regulatory networks associated with pineal gland evolution and function. Our study provides a detailed analysis of the pineal gland's evolution from fish to mammals. We identified key transcriptional changes and controls that highlight the gland's functional diversity. Notably, we found significant ligand‐receptor interactions influencing melatonin synthesis and demonstrated parallels between pineal and retinal expressions. These insights enhance our understanding of the pineal gland's role in phototransduction, melatonin production, and circadian rhythms in vertebrates.

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Integrated analysis of multimodal single-cell data with structural similarity

Cited by 54 publications

References 52 publications

Ex vivoExpansion Potential of Murine Hematopoietic Stem Cells: A Rare Property Only Partially Predicted by Phenotype

Ex vivoExpansion Potential of Murine Hematopoietic Stem Cells: A Rare Property Only Partially Predicted by Phenotype

Prognostic and immunotherapeutic potential of regulatory T cell‐associated signature in ovarian cancer

Cross‐species single‐cell landscape of vertebrate pineal gland

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