An interpretable single-cell RNA sequencing data clustering method based on latent Dirichlet allocation DOI Creative Commons
Qi Yang, Zhaochun Xu, Wenyang Zhou

et al.

Briefings in Bioinformatics, Journal Year: 2023, Volume and Issue: 24(4)

Published: May 23, 2023

Single-cell RNA sequencing (scRNA-seq) detects whole transcriptome signals for large amounts of individual cells and is powerful determining cell-to-cell differences investigating the functional characteristics various cell types. scRNA-seq datasets are usually sparse highly noisy. Many steps in analysis workflow, including reasonable gene selection, clustering annotation, as well discovering underlying biological mechanisms from such datasets, difficult. In this study, we proposed an method based on latent Dirichlet allocation (LDA) model. The LDA model estimates a series variables, i.e. putative functions (PFs), input raw cell-gene data. Thus, incorporated 'cell-function-gene' three-layer framework into analysis, capable complex expression patterns via built-in approach obtaining biologically meaningful results through data-driven interpretation process. We compared our with four classic methods seven benchmark datasets. LDA-based performed best test terms both accuracy purity. By analysing three public demonstrated that could distinguish types multiple levels specialization, precisely reconstruct development trajectories. Moreover, accurately identified representative PFs genes types/cell stages, enabling cluster annotation interpretation. According to literature, most previously reported marker/functionally relevant were recognized.

Language: Английский

Analysis and Visualization of Spatial Transcriptomic Data DOI Creative Commons
Boxiang Liu, Yanjun Li, Liang Zhang

et al.

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 27, 2022

Human and animal tissues consist of heterogeneous cell types that organize interact in highly structured manners. Bulk single-cell sequencing technologies remove cells from their original microenvironments, resulting a loss spatial information. Spatial transcriptomics is recent technological innovation measures transcriptomic information while preserving data can be generated several ways. RNA molecules are measured by

Language: Английский

Citations

54
Spatial-ID: a cell typing method for spatially resolved transcriptomics via transfer learning and spatial embedding DOI Creative Commons
Rongbo Shen, Lin Liu, Zihan Wu

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Dec. 10, 2022

Spatially resolved transcriptomics provides the opportunity to investigate gene expression profiles and spatial context of cells in naive state, but at low transcript detection sensitivity or with limited throughput. Comprehensive annotating cell types spatially understand biological processes single level remains challenging. Here we propose Spatial-ID, a supervision-based typing method, that combines existing knowledge reference single-cell RNA-seq data information data. We present series benchmarking analyses on publicly available datasets, demonstrate superiority Spatial-ID compared state-of-the-art methods. Besides, apply self-collected mouse brain hemisphere dataset measured by Stereo-seq, shows scalability three-dimensional large field tissues subcellular resolution.

Language: Английский

Citations

52
SIMBA: single-cell embedding along with features DOI Creative Commons
Huidong Chen, Jayoung Ryu, Michael Vinyard

et al.

Nature Methods, Journal Year: 2023, Volume and Issue: 21(6), P. 1003 - 1013

Published: May 29, 2023

Abstract Most current single-cell analysis pipelines are limited to cell embeddings and rely heavily on clustering, while lacking the ability explicitly model interactions between different feature types. Furthermore, these methods tailored specific tasks, as distinct problems formulated differently. To address shortcomings, here we present SIMBA, a graph embedding method that jointly embeds single cells their defining features, such genes, chromatin-accessible regions DNA sequences, into common latent space. By leveraging co-embedding of SIMBA allows for study cellular heterogeneity, clustering-free marker discovery, gene regulation inference, batch effect removal omics data integration. We show provides framework diverse be in unified way thus simplifies development new analyses extension modalities. is implemented comprehensive Python library ( https://simba-bio.readthedocs.io ).

Language: Английский

Citations

38
Neonatal imprinting of alveolar macrophages via neutrophil-derived 12-HETE DOI Creative Commons
Erwan Pernet,

Sarah Sun,

Nicole Sarden

et al.

Nature, Journal Year: 2023, Volume and Issue: 614(7948), P. 530 - 538

Published: Jan. 4, 2023

Resident-tissue macrophages (RTMs) arise from embryonic precursors1,2, yet the developmental signals that shape their longevity remain largely unknown. Here we demonstrate in mice genetically deficient 12-lipoxygenase and 15-lipoxygenase (Alox15-/- mice) neonatal neutrophil-derived 12-HETE is required for self-renewal maintenance of alveolar (AMs) during lung development. Although seeding differentiation AM progenitors remained intact, absence led to a significant reduction AMs adult lungs enhanced senescence owing increased prostaglandin E2 production. A compromised compartment resulted susceptibility acute injury induced by lipopolysaccharide pulmonary infections with influenza virus or SARS-CoV-2. Our results highlight complexity prenatal RTM programming reveal dependency on trans eicosanoid production neutrophils lifelong self-renewal.

Language: Английский

Citations

37
Gut microbiota aggravates neutrophil extracellular traps-induced pancreatic injury in hypertriglyceridemic pancreatitis DOI Creative Commons
Guanqun Li, Liwei Liu, Tianqi Lu

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 4, 2023

Hypertriglyceridemic pancreatitis (HTGP) is featured by higher incidence of complications and poor clinical outcomes. Gut microbiota dysbiosis associated with pancreatic injury in HTGP the mechanism remains unclear. Here, we observe lower diversity gut absence beneficial bacteria patients. In a fecal transplantation mouse model, colonization from patients recruits neutrophils increases neutrophil extracellular traps (NETs) formation that exacerbates systemic inflammation. We find decreased abundance Bacteroides uniformis impairs taurine production IL-17 release colon triggers NETs formation. Moreover, or inhibits activation NF-κB signaling pathways which harness alleviate injury. Our findings establish roles endogenous uniformis-derived metabolic inflammatory products on suppressing release, provides potential insights ameliorating through modulation.

Language: Английский

Citations

36
To bind or not to bind: how AUXIN RESPONSE FACTORs select their target genes DOI Creative Commons
Juriaan Rienstra, Jorge Hernández‐García, Dolf Weijers

et al.

Journal of Experimental Botany, Journal Year: 2023, Volume and Issue: 74(22), P. 6922 - 6932

Published: July 11, 2023

Abstract Most plant growth and development processes are regulated in one way or another by auxin. The best-studied mechanism which auxin exerts its regulatory effects is through the nuclear pathway (NAP). In this pathway, Auxin Response Factors (ARFs) transcription factors that ultimately determine genes become binding to specific DNA sequences. ARFs have primarily been studied Arabidopsis thaliana, but recent studies other species revealed family-wide specificities for different minimal functional system of NAP system, consisting a duo competing A B classes. review, we provide an overview key aspects ARF such as response elements (TGTCNN) tandem repeat motifs, consider how structural biology vitro help us understand preferences. We also highlight some related regulation levels inside cell, may alter profile tissues. finally emphasize need study systems fundamental function, characterize algal evolved, cutting-edge techniques can increase our understanding ARFs, remaining questions only be answered biology.

Language: Английский

Citations

24
BCG vaccination alters the epigenetic landscape of progenitor cells in human bone marrow to influence innate immune responses DOI
Sarah Sun, Raúl Aguirre‐Gamboa, L. Charlotte J. de Bree

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(9), P. 2095 - 2107.e8

Published: Aug. 16, 2024

Language: Английский

Citations

16
The Alzheimer’s disease risk gene BIN1 regulates activity-dependent gene expression in human-induced glutamatergic neurons DOI Creative Commons
Orthis Saha, Ana Raquel Melo de Farias, Alexandre Pelletier

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(9), P. 2634 - 2646

Published: March 22, 2024

Bridging Integrator 1 (BIN1) is the second most important Alzheimer's disease (AD) risk gene, but its physiological roles in neurons and contribution to brain pathology remain largely elusive. In this work, we show that BIN1 plays a critical role regulation of calcium homeostasis, electrical activity, gene expression glutamatergic neurons. Using single-cell RNA-sequencing on cerebral organoids generated from isogenic wild type (WT), heterozygous (HET) homozygous knockout (KO) human-induced pluripotent stem cells (hiPSCs), mainly expressed by oligodendrocytes neurons, like human brain. Both HET KO specific transcriptional alterations, associated with ion transport synapses We then demonstrate cell-autonomously regulates using novel protocol generate pure culture hiPSC-derived induced (hiNs). system, also key neuronal transients activity via interaction L-type voltage-gated channel Cav

Language: Английский

Citations

14
Single-cell profiling of response to neoadjuvant chemo-immunotherapy in surgically resectable esophageal squamous cell carcinoma DOI Creative Commons
Gang Ji, Qi Yang, Song Wang

et al.

Genome Medicine, Journal Year: 2024, Volume and Issue: 16(1)

Published: April 2, 2024

Abstract Background The efficacy of neoadjuvant chemo-immunotherapy (NAT) in esophageal squamous cell carcinoma (ESCC) is challenged by the intricate interplay within tumor microenvironment (TME). Unveiling immune landscape ESCC context NAT could shed light on heterogeneity and optimize therapeutic strategies for patients. Methods We analyzed single cells from 22 baseline 24 post-NAT treatment samples stage II/III patients to explore association between pathological response anti-PD-1 combination therapy, including complete (pCR), major (MPR), incomplete (IPR). Results Single-cell profiling identified 14 subsets cancer, immune, stromal cells. Trajectory analysis unveiled an interesting link cancer differentiation NAT. tumors enriched with less differentiated exhibited a potentially favorable NAT, while clusters more may resist treatment. Deconvolution transcriptomes pre-treatment gene signatures contributed specific populations. Upregulated genes associated better responses CD8 + effector T primarily involved interferon-gamma (IFNγ) signaling, neutrophil degranulation, negative regulation apoptotic process, whereas downregulated were dominated those response-activating surface receptor signaling pathway. Natural killer pCR showed similar upregulation expression IFNγ but downregulation neutrophil-mediated immunity pathways. A decreased cellular contexture regulatory TME indicated Cell–cell communication revealed extensive interactions CCL5 its CCR5 various tumors. Immune checkpoint interaction pairs, CTLA4-CD86, TIGIT-PVR, LGALS9-HAVCR2, TNFSF4-TNFRSF4, might serve as additional targets ICI therapy ESCC. Conclusions This pioneering study intriguing patients, revealing distinct subgroups which be effective. also delineated clinical provides insights understanding how respond further identifying novel future.

Language: Английский

Citations

11
Single-cell omics: experimental workflow, data analyses and applications DOI
Fengying Sun, Haoyan Li, Dongqing Sun

et al.

Science China Life Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: July 23, 2024

Language: Английский

Citations

11