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1

Song, Zheng, Likai Tan та Immo Prinz. "Human γδ T cell identification from single-cell RNA sequencing datasets by modular TCR expression". Journal of Leukocyte Biology 114, № 6 (2023): 630–38. https://doi.org/10.5281/zenodo.7989561.

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Accurately identifying γδ T cells in large single-cell RNA sequencing (scRNA-seq) datasets without additional single-cell γδ T cell receptor sequencing (sc-γδTCR-seq) or CITE-seq (cellular indexing of transcriptomes and epitopes sequencing) data remains challenging. In this study, we developed a TCR module scoring strategy for human γδ T cell identification (i.e. based on modular gene expression of constant and variable TRA/TRB and TRD genes). We evaluated our method using 5' scRNA-seq datasets comprising both sc-αβTCR-seq and sc-&gamm
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Ma, Shi-Xun, and Su Bin Lim. "Single-Cell RNA Sequencing in Parkinson’s Disease." Biomedicines 9, no. 4 (2021): 368. http://dx.doi.org/10.3390/biomedicines9040368.

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Single-cell and single-nucleus RNA sequencing (sc/snRNA-seq) technologies have enhanced the understanding of the molecular pathogenesis of neurodegenerative disorders, including Parkinson’s disease (PD). Nonetheless, their application in PD has been limited due mainly to the technical challenges resulting from the scarcity of postmortem brain tissue and low quality associated with RNA degradation. Despite such challenges, recent advances in animals and human in vitro models that recapitulate features of PD along with sequencing assays have fueled studies aiming to obtain an unbiased and global
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Biancalani, Tommaso, Gabriele Scalia, Lorenzo Buffoni, et al. "Deep learning and alignment of spatially resolved single-cell transcriptomes with Tangram." Nature Methods 18, no. 11 (2021): 1352–62. http://dx.doi.org/10.1038/s41592-021-01264-7.

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AbstractCharting an organs’ biological atlas requires us to spatially resolve the entire single-cell transcriptome, and to relate such cellular features to the anatomical scale. Single-cell and single-nucleus RNA-seq (sc/snRNA-seq) can profile cells comprehensively, but lose spatial information. Spatial transcriptomics allows for spatial measurements, but at lower resolution and with limited sensitivity. Targeted in situ technologies solve both issues, but are limited in gene throughput. To overcome these limitations we present Tangram, a method that aligns sc/snRNA-seq data to various forms o
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Li, Chunbao, Mingyang An, Yang He, and Zhongyuan Zhao. "FP3.3 Single-cell RNA-seq analysis reveals a new mechanism of cartilage formation from the synovium in synovial chondromatosis." Journal of Hip Preservation Surgery 12, Supplement_1 (2025): i7. https://doi.org/10.1093/jhps/hnaf011.021.

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Abstract Objective: Cartilage repair remains a challenging medical issue with a lack of effective solutions to date. Synovial chondromatosis (SC) is a rare benign tumor caused by synovial metaplasia. A characteristic feature of SC is the synovium’s spontaneous ability to form translucent cartilage nodules. Currently, the molecular mechanisms behind spontaneous cartilage formation in vivo are poorly understood. Our study aims to investigate the mechanisms of chondrogenesis in SC and the dynamic changes between cell subpopulations at the cellular level using single-cell sequencing technology. Me
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Ajani, Jaffer A., Yan Xu, Longfei Huo, et al. "YAP1 mediates gastric adenocarcinoma peritoneal metastases that are attenuated by YAP1 inhibition." Gut 70, no. 1 (2020): 55–66. http://dx.doi.org/10.1136/gutjnl-2019-319748.

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ObjectivePeritoneal carcinomatosis (PC; malignant ascites or implants) occurs in approximately 45% of advanced gastric adenocarcinoma (GAC) patients and associated with a poor survival. The molecular events leading to PC are unknown. The yes-associated protein 1 (YAP1) oncogene has emerged in many tumour types, but its clinical significance in PC is unclear. Here, we investigated the role of YAP1 in PC and its potential as a therapeutic target.MethodsPatient-derived PC cells, patient-derived xenograft (PDX) and patient-derived orthotopic (PDO) models were used to study the function of YAP1 in
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Si, Tong, Zackary Hopkins, John Yanev, Jie Hou, and Haijun Gong. "A novel f-divergence based generative adversarial imputation method for scRNA-seq data analysis." PLOS ONE 18, no. 11 (2023): e0292792. http://dx.doi.org/10.1371/journal.pone.0292792.

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Comprehensive analysis of single-cell RNA sequencing (scRNA-seq) data can enhance our understanding of cellular diversity and aid in the development of personalized therapies for individuals. The abundance of missing values, known as dropouts, makes the analysis of scRNA-seq data a challenging task. Most traditional methods made assumptions about specific distributions for missing values, which limit their capability to capture the intricacy of high-dimensional scRNA-seq data. Moreover, the imputation performance of traditional methods decreases with higher missing rates. We propose a novel f-
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Li, Shenghao, Hui Guo, Simai Zhang, Yizhou Li, and Menglong Li. "Attention-based deep clustering method for scRNA-seq cell type identification." PLOS Computational Biology 19, no. 11 (2023): e1011641. http://dx.doi.org/10.1371/journal.pcbi.1011641.

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Single-cell sequencing (scRNA-seq) technology provides higher resolution of cellular differences than bulk RNA sequencing and reveals the heterogeneity in biological research. The analysis of scRNA-seq datasets is premised on the subpopulation assignment. When an appropriate reference is not available, such as specific marker genes and single-cell reference atlas, unsupervised clustering approaches become the predominant option. However, the inherent sparsity and high-dimensionality of scRNA-seq datasets pose specific analytical challenges to traditional clustering methods. Therefore, a variou
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Lall, Snehalika, Sumanta Ray, and Sanghamitra Bandyopadhyay. "A copula based topology preserving graph convolution network for clustering of single-cell RNA-seq data." PLOS Computational Biology 18, no. 3 (2022): e1009600. http://dx.doi.org/10.1371/journal.pcbi.1009600.

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Annotation of cells in single-cell clustering requires a homogeneous grouping of cell populations. There are various issues in single cell sequencing that effect homogeneous grouping (clustering) of cells, such as small amount of starting RNA, limited per-cell sequenced reads, cell-to-cell variability due to cell-cycle, cellular morphology, and variable reagent concentrations. Moreover, single cell data is susceptible to technical noise, which affects the quality of genes (or features) selected/extracted prior to clustering. Here we introduce sc-CGconv (copula based graph convolution network f
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Hanamsagar, Richa, Robert Marcus, Mathew Chamberlain, Emanuele de Rinaldis, and Virginia Savova. "Optimum processing conditions for single cell RNA sequencing on frozen human PBMCs." Journal of Immunology 202, no. 1_Supplement (2019): 131.15. http://dx.doi.org/10.4049/jimmunol.202.supp.131.15.

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Abstract The field of single cell RNA sequencing (sc-SEQ) has exploded in the past few years. From picking up single cells manually under a microscope, to droplet-based encapsulation of cells using microfluidics – this technology has improved in leaps and bounds. Common droplet-based technologies include inDrop, Drop-seq and 10X Genomics Chromium. All three technologies utilize microfluidics for encapsulating single cells & uniquely barcoded beads within an oil droplet. They differ in their bead material/manufacturing, barcode design and the range to which their operation can be customized
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Hagemann, Tobias, Paul Czechowski, Adhideb Ghosh та ін. "Laminin α4 Expression in Human Adipose Tissue Depots and Its Association with Obesity and Obesity Related Traits". Biomedicines 11, № 10 (2023): 2806. http://dx.doi.org/10.3390/biomedicines11102806.

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Laminin α4 (LAMA4) is one of the main structural adipocyte basement membrane (BM) components that is upregulated during adipogenesis and related to obesity in mice and humans. We conducted RNA-seq-based gene expression analysis of LAMA4 in abdominal subcutaneous (SC) and visceral (VIS) adipose tissue (AT) depots across three human sub-cohorts of the Leipzig Obesity BioBank (LOBB) to explore the relationship between LAMA4 expression and obesity (N = 1479) in the context of weight loss (N = 65) and metabolic health (N = 42). We found significant associations of LAMA4 with body fat mass (p < 0
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Le, Huy, Beverly Peng, Janelle Uy, et al. "Machine learning for cell type classification from single nucleus RNA sequencing data." PLOS ONE 17, no. 9 (2022): e0275070. http://dx.doi.org/10.1371/journal.pone.0275070.

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With the advent of single cell/nucleus RNA sequencing (sc/snRNA-seq), the field of cell phenotyping is now a data-driven exercise providing statistical evidence to support cell type/state categorization. However, the task of classifying cells into specific, well-defined categories with the empirical data provided by sc/snRNA-seq remains nontrivial due to the difficulty in determining specific differences between related cell types with close transcriptional similarities, resulting in challenges with matching cell types identified in separate experiments. To investigate possible approaches to o
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Mahajan, Nitin, Laura Arthur, Jayakumar Vadakekolathu, John Muth, Jan K. Davidson-Moncada, and Sergio Rutella. "Single-Cell Transcriptional Landscape of W-NK1, an Off-the-Shelf Natural Killer Cell Therapy." Blood 144, Supplement 1 (2024): 7184. https://doi.org/10.1182/blood-2024-201496.

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Background Natural killer (NK) cells play a critical role in tumor eradication. W-NK1 is a non-edited, cryopreserved off-the-shelf NK cell therapy product with a ‘memory-like’ phenotype that addresses challenges faced by adoptive cell therapies, such as poor resilience to adverse and immunosuppressive tumor microenvironments (TME). W-NK1 not only overcomes nutrient deprivation, inhibitory ligands, and reduced chemokine expression in the TME, but also recruits and activates dendritic and T cells through cytokine and chemokine production, thereby enhancing the overall immune response. This study
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13

Lehman, Bettina J., Fernando J. Lopez-Diaz, Thom P. Santisakultarm, et al. "Dynamic regulation of CTCF stability and sub-nuclear localization in response to stress." PLOS Genetics 17, no. 1 (2021): e1009277. http://dx.doi.org/10.1371/journal.pgen.1009277.

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The nuclear protein CCCTC-binding factor (CTCF) has diverse roles in chromatin architecture and gene regulation. Functionally, CTCF associates with thousands of genomic sites and interacts with proteins, such as cohesin, or non-coding RNAs to facilitate specific transcriptional programming. In this study, we examined CTCF during the cellular stress response in human primary cells using immune-blotting, quantitative real time-PCR, chromatin immunoprecipitation-sequence (ChIP-seq) analysis, mass spectrometry, RNA immunoprecipitation-sequence analysis (RIP-seq), and Airyscan confocal microscopy.
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Noguchi, Kazuhiro, Yasuhiro Ikawa, Mika Takenaka, Yuta Sakai, Toshihiro Fujiki, and Taizo Wada. "SPI1 Is the Master Regulator of the Small Cell Variant of Anaplastic Large Cell Lymphoma Controlled By Methylation of SPI1 Gene Promoter Region." Blood 142, Supplement 1 (2023): 6093. http://dx.doi.org/10.1182/blood-2023-179674.

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Introduction The small cell variant of anaplastic large cell lymphoma (SC-ALCL) is a subtype of anaplastic lymphoma kinase (ALK)-positive ALCL characterized by chemoresistance and poor prognosis, necessitating novel treatment strategies. Recent advances in targeted therapies have resulted in significant responses in various chemoresistant hematological malignancies. Therefore, understanding the underlying oncogenic mechanisms and identifying potential therapeutic targets are critical for overcoming SC-ALCL. Immunohistochemically, SC-ALCL comprises two distinct tumor cell populations: small tum
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Ciortan, Madalina, and Matthieu Defrance. "GNN-based embedding for clustering scRNA-seq data." Bioinformatics 38, no. 4 (2021): 1037–44. http://dx.doi.org/10.1093/bioinformatics/btab787.

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Abstract Motivation Single-cell RNA sequencing (scRNA-seq) provides transcriptomic profiling for individual cells, allowing researchers to study the heterogeneity of tissues, recognize rare cell identities and discover new cellular subtypes. Clustering analysis is usually used to predict cell class assignments and infer cell identities. However, the high sparsity of scRNA-seq data, accentuated by dropout events generates challenges that have motivated the development of numerous dedicated clustering methods. Nevertheless, there is still no consensus on the best performing method. Results graph
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Liu, Chuan-He, Yan Liu, Xue-Hua Shao, and Duo Lai. "Comparative Analyses of the Transcriptome and Proteome of Comte de Paris and Smooth Cayenne to Improve the Understanding of Ethephon-Induced Floral Transition in Pineapple." Cellular Physiology and Biochemistry 50, no. 6 (2018): 2139–56. http://dx.doi.org/10.1159/000495057.

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Background/Aims: Ethylene is usually used to induce floral transition in pineapple. However, its successful induction in plants categorized as Cayenne is difficult or completely ineffective, and information concerned is limited. The present study was undertaken to investigate the molecular mechanisms underlying this obstacle. Methods: Transcriptome and proteome comparative analyses were performed to explore the important regulation and pathway variations after ethephon induction in the induction-easy ‘Comte de Paris’ (CP) and induction-hard ‘Smooth Cayenne’ (SC) cultivars via RNA-seq (RNA-sequ
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Tang, Binqing, Yingen Wu, Hong Fang, Yuqin Wu, and Kehua Shi. "Small RNA Sequencing Reveals Exosomal miRNAs Involved in the Treatment of Asthma by Scorpio and Centipede." BioMed Research International 2020 (January 16, 2020): 1–12. http://dx.doi.org/10.1155/2020/1061407.

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Asthma is a common respiratory disease with inflammation in the lungs. Exosomes and microRNAs (miRNAs) play crucial role in inflammation, whereas the role of exosomal miRNA in asthma remains unknown. Here, we aimed to identify the key exosomal miRNAs and their underlying mechanisms involved in scorpio and centipede (SC) treatment in asthma. Eighteen mice were randomly divided into three groups: control group, asthma group, and SC treatment group. Effect of SC was assessed by hematoxylin-eosin staining and real-time PCR. Exosomes from asthma and SC treatment groups were analyzed by small RNA-se
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Deeke, Julie M., and Johann A. Gagnon-Bartsch. "Stably expressed genes in single-cell RNA sequencing." Journal of Bioinformatics and Computational Biology 18, no. 01 (2020): 2040004. http://dx.doi.org/10.1142/s0219720020400041.

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Motivation: In single-cell RNA-sequencing (scRNA-seq) experiments, RNA transcripts are extracted and measured from isolated cells to understand gene expression at the cellular level. Measurements from this technology are affected by many technical artifacts, including batch effects. In analogous bulk gene expression experiments, external references, e.g. synthetic gene spike-ins often from the External RNA Controls Consortium (ERCC), may be incorporated to the experimental protocol for use in adjusting measurements for technical artifacts. In scRNA-seq experiments, the use of external spike-in
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Velalopoulou, Anastasia, Ilias V. Karagounis, Giorgos Skoufos, et al. "Abstract 3304: Gene expression profiling of full-thickness skin after FLASH proton radiotherapy." Cancer Research 82, no. 12_Supplement (2022): 3304. http://dx.doi.org/10.1158/1538-7445.am2022-3304.

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Abstract Purpose: To investigate the transcriptomic changes induced by FLASH proton radiotherapy (F-PRT) that could be responsible for the protection of normal epithelial tissues by radiation-induced toxicities as have been previously shown by us and others. Methods: C57BL/6J mice received 30 Gy of F-PRT or S-PRT to the hind leg at respective dose rates of 69-124 Gy/sec or 0.39-0.65 Gy/sec. RNA sequencing was performed using full-thickness leg skin at 5 days after radiation revealing major pathways regulated by F-PRT and S-PRT. In an endeavor to identify the full repertoire of cells and gene e
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Grigoryeva, E., L. Tashireva, V. V. Alifanov, et al. "485P A novel approach to identify subpopulation of CTCs with metastatic potential using sc-RNA-seq." Annals of Oncology 34 (October 2023): S385—S386. http://dx.doi.org/10.1016/j.annonc.2023.09.661.

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Katims, Andrew B., Fengshen Kuo, Peter Reisz, et al. "Characterizing the immune phenotype of FGFR3 mutated upper tract urothelial carcinoma (UTUC) using single-cell (sc)RNA-sequencing (seq)." Journal of Clinical Oncology 41, no. 6_suppl (2023): 558. http://dx.doi.org/10.1200/jco.2023.41.6_suppl.558.

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558 Background: Fibroblast growth factor 3 (FGFR3) is the most common mutation in UTUC and is altered in approximately 75% of tumors. Tumors harboring FGFR3 mutations (FGFR3-M) have a T-cell impaired tumor microenvironment (TME) which may explain the incomplete response to immune checkpoint blockade. We performed scRNA-seq on 8 untreated tumors to further characterize the T-cell immune phenotype of FGFR3-M tumors. Methods: scRNA-seq (10x Genomics platform) was performed on 8 UTUC tissue specimens from 8 different patients who had not received treatment (chemotherapy or immunotherapy) using an
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Dadey, Rebekah E., Ruxuan Li, Jake Griner, et al. "Multiomics identifies tumor-intrinsic SREBP1 driving immune exclusion in hepatocellular carcinoma." Journal for ImmunoTherapy of Cancer 13, no. 6 (2025): e011537. https://doi.org/10.1136/jitc-2025-011537.

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Immune checkpoint inhibitors (ICI) have improved patient outcomes in hepatocellular carcinoma (HCC); however, most patients do not experience durable benefit. The non-T cell-inflamed tumor microenvironment, characterized by limited CD8+T-cell infiltration, reduced dendritic cell function, and low interferon-γ-associated gene expression, is associated with a lower likelihood of response to ICI. To nominate new therapeutic targets for overcoming ICI resistance in HCC, we conducted a large-scale multiomic analysis on 900+human specimens (RNA sequencing (RNA-seq), proteomics) and 31 tumor single-c
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Singh, Komudi, Michelle Baird, Robert Fischer, et al. "Misregulation of ELK1, AP1, and E12 Transcription Factor Networks Is Associated with Melanoma Progression." Cancers 12, no. 2 (2020): 458. http://dx.doi.org/10.3390/cancers12020458.

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Melanoma is among the most malignant cutaneous cancers and when metastasized results in dramatically high mortality. Despite advances in high-throughput gene expression profiling in cancer transcriptomic studies, our understanding of mechanisms driving melanoma progression is still limited. We present here an in-depth bioinformatic analysis of the melanoma RNAseq, chromatin immunoprecipitation (ChIP)seq, and single-cell (sc)RNA seq data to understand cancer progression. Specifically, we have performed a consensus network analysis of RNA-seq data from clinically re-grouped melanoma samples to i
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Shimizu, Takuya, Takero Shindo, Akira Watanabe, and Akifumi Takaori-Kondo. "Single-Cell RNA Sequencing Revealed the YY1/EZH2/MLH1 Axis As a Possible Therapeutic Target of Intractable Adult T-Cell Leukemia." Blood 142, Supplement 1 (2023): 6084. http://dx.doi.org/10.1182/blood-2023-185712.

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Background: Due to clinical heterogeneity of adult T-cell leukemia/lymphoma (ATL) and its diverse genetic abnormality, common therapeutic targets of ATL remains unclear. Whereas the YY1/EZH2 axis regulates global epigenetic modification of genes in ATL, its downstream target genes have not been fully elucidated. Meanwhile, DNA mismatch repair proteins may be targeted in ATL. Here we explored underlying molecular axes for ATL progression through comprehensive single-cell RNA-sequencing (sc-RNA-seq). Methods: Peripheral blood of 42 ATL patients and asymptomatic HTLV-1 carriers in addition to two
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Yoo, Yun Jae, Ki H. Oh, Luke A. Torre-Healy, and Richard A. Moffitt. "Abstract A058: Meta-analysis of single-cell RNA expression in genetically engineered mouse models of pancreatic ductal adenocarcinoma reveals inter-model heterogeneity." Cancer Research 82, no. 22_Supplement (2022): A058. http://dx.doi.org/10.1158/1538-7445.panca22-a058.

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Abstract Background: Genetically engineered mouse models (GEMMs) are widely used in the study of pancreatic ductal adenocarcinoma (PDAC) because of their immune-competent tumor microenvironment (TME); however, the extent to which particular GEMMs recapitulate the tumor and TME observed in the patient population has not been systematically evaluated. In this study, we integrate single-cell RNA sequencing (sc-RNA-seq) data from multiple studies and multiple GEMM backgrounds to identify differences in the cellular compositions of popular PDAC GEMMs. Methods: A total of 49,191 cells were used from
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Garg, Bharti, Evangeline S. Mose, Edgar Esparaze, et al. "Abstract 2582: Silencing MICAL2 expression in pancreatic cancer cells rewires the tumor microenvironment through the IL1-a/p38 MAP kinase/STAT-3 axis and sensitizes tumors to immune checkpoint blockade therapy." Cancer Research 85, no. 8_Supplement_1 (2025): 2582. https://doi.org/10.1158/1538-7445.am2025-2582.

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Abstract Introduction: PDAC, characterized by fibroinflammatory stroma, involves cancer cell-microenvironment interactions driving progression and resistance. ChIP-seq on resected PDAC samples identified MICAL2 as a super-enhancer-associated gene involved in tumor progression. MICAL2, a flavin monooxygenase, promotes actin depolymerization and SRF transcription. This study evaluates how MICAL2 in tumor cells affects the PDAC microenvironment via the IL1-a/p38 MAP kinase/STAT3 axis. Methods: AsPC-1 and KPC-Shcontrol (ShCNT) and MICAL2 (M2KD) cells were injected to assess tumor growth. Sc-RNA se
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Rehn, Jacqueline, Chelsea Mayoh, Susan L. Heatley, et al. "Rascall: Rapid (Ra) screening (Sc) of RNA-seq data for prognostically significant genomic alterations in acute lymphoblastic leukaemia (ALL)." PLOS Genetics 18, no. 10 (2022): e1010300. http://dx.doi.org/10.1371/journal.pgen.1010300.

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RNA-sequencing (RNA-seq) efforts in acute lymphoblastic leukaemia (ALL) have identified numerous prognostically significant genomic alterations which can guide diagnostic risk stratification and treatment choices when detected early. However, integrating RNA-seq in a clinical setting requires rapid detection and accurate reporting of clinically relevant alterations. Here we present RaScALL, an implementation of the k-mer based variant detection tool km, capable of identifying more than 100 prognostically significant lesions observed in ALL, including gene fusions, single nucleotide variants an
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Gupta, Pravesh, Minghao Dang, Dapeng Hao Hao, et al. "IMMU-43. IMMUNE CONTEXTURE OF ISOCITRATE DEHYDROGENASE STRATIFIED HUMAN GLIOMAS REVEALED BY SINGLE-CELL TRANSCRIPTOMICS AND ACCESSIBLE CHROMATIN." Neuro-Oncology 23, Supplement_6 (2021): vi102. http://dx.doi.org/10.1093/neuonc/noab196.402.

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Abstract The immune cell composition of isocitrate dehydrogenase wild type (IDH-wt) glioma patients significantly differs compared to IDH-mutant (IDH-mut) yet a detailed and unbiased understanding of their transcriptomic and epigenetic landscapes remains elusive. To this end, we performed single-cell RNA-sequencing (scRNA-seq) and single-cell Assay for Transposase-Accessible Chromatin using sequencing (sc-ATAC-seq) on ~100,000 tumor-associated immune cells from seventeen IDH mutation classified primary and recurrent human gliomas and non-glioma brains (NGBs). Our analyses revealed sixty-two tr
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Zeng, Andy G. X., Ilaria Iacobucci, Sayyam Shah, et al. "Precise Single-Cell Transcriptomic Mapping of Leukemia Cell States Reveals Unconventional Lineage Priming in Acute Myeloid Leukemia." Blood 142, Supplement 1 (2023): 1593. http://dx.doi.org/10.1182/blood-2023-189697.

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Initial disease classification within acute leukemia relies on identifying morphological and immunophenotypic features of hematopoietic differentiation retained by leukemic blasts. While existing approaches can classify leukemic cells into broad lineages, they lack precision in discerning between specific cell states, particularly at the level of immature blasts. Single-cell (sc) RNA-sequencing (RNA-seq) provides thousands of new markers to enable precise determination of leukemia cell state and provides an opportunity to refine our classification of acute leukemia. To extend our ability to id
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Vukojicic, Nevena, Aleksandar Danicic, Zelia Worman, et al. "Abstract 2075: Highly customizable multi-sample single cell RNA-Seq pipeline on the CGC." Cancer Research 83, no. 7_Supplement (2023): 2075. http://dx.doi.org/10.1158/1538-7445.am2023-2075.

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Abstract Single-cell (sc) transcriptomics has revolutionized our understanding of the biological characteristics and dynamics of cancer development. It can help us identify rare cell subpopulations and understand mechanisms associated with tumor genesis, progression, and response to therapy. The most important step in the analyses of any scRNA-seq dataset is subpopulation identification, usually performed via unsupervised clustering, followed by gene marker identification. We created a highly customizable workflow for sc data analysis, implemented in Common Workflow Language (CWL) on the Cance
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Guo, Shuai, Xuesen Cheng, Andrew Koval, et al. "Abstract 4273: Integration with benchmark data of paired bulk and single-cell RNA sequencing data substantially improves the accuracy of bulk tissue deconvolution." Cancer Research 83, no. 7_Supplement (2023): 4273. http://dx.doi.org/10.1158/1538-7445.am2023-4273.

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Abstract The accuracy of current deconvolution methods largely relies on the quality of cell-type expression references. However, single-cell (sc) and single-nuclei (sn) RNA-seq data used for building the reference are usually generated from independent studies that are distinct from the bulk RNA-seq data to be deconvolved. This study design inherently introduces technical confounding factors as unwanted variations, which is not fully addressed by current methods. To evaluate the impact of this variation on deconvolution accuracy, we generated a benchmark dataset where bulk and snRNA-seq profi
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Sehgal, Kartik, Andrew Portell, Elena Ivanova, et al. "248 Immunotherapy persister cells uncovered by dynamic single-cell RNA-sequencing." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (2020): A268—A269. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0248.

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BackgroundTo understand fundamental mechanisms of immune escape, we leveraged our functional ex vivo platform of murine derived organotypic tumor spheroids (DOTS)1 to determine if drug-tolerant persister cells analogous to oncogene targeted therapies limit efficacy of programmed death (PD)-1 blockade, and to identify therapeutic vulnerabilities to overcome anti-PD-1 (αPD-1) resistance.MethodsMurine syngeneic cancer models with well-characterized response to αPD-1 therapy were chosen: MC38 (sensitive) and CT26 (partially resistant). Bulk and single-cell (sc) RNA-sequencing (RNA-seq) were perfor
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Timperi, Eleonora, and Emanuela Romano. "Stromal circuits involving tumor-associated macrophages and cancer-associated fibroblasts." Frontiers in Immunology 14 (June 5, 2023). http://dx.doi.org/10.3389/fimmu.2023.1194642.

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The tumor associated macrophages (TAM) represent one of most abundant subpopulations across several solid cancers and their number/frequency is associated with a poor clinical outcome. It has been clearly demonstrated that stromal cells, such as the cancer associated fibroblasts (CAFs), may orchestrate TAM recruitment, survival and reprogramming. Today, single cell-RNA sequencing (sc-RNA seq) technologies allowed a more granular knowledge about TAMs and CAFs phenotypical and functional programs. In this mini-review we discuss the recent discoveries in the sc-RNA seq field focusing on TAM and C
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Berg, Marijn, Ilya Petoukhov, Inge van den Ende, et al. "FastCAR: fast correction for ambient RNA to facilitate differential gene expression analysis in single-cell RNA-sequencing datasets." BMC Genomics 24, no. 1 (2023). http://dx.doi.org/10.1186/s12864-023-09822-3.

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AbstractCell type-specific differential gene expression analyses based on single-cell transcriptome datasets are sensitive to the presence of cell-free mRNA in the droplets containing single cells. This so-called ambient RNA contamination may differ between samples obtained from patients and healthy controls. Current ambient RNA correction methods were not developed specifically for single-cell differential gene expression (sc-DGE) analyses and might therefore not sufficiently correct for ambient RNA-derived signals. Here, we show that ambient RNA levels are highly sample-specific. We found th
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Song, Zheng, Lara Henze, Christian Casar та ін. "Human γδ T cell Identification from Single-cell RNA Sequencing Datasets by Modular TCR Expression". Journal of Leukocyte Biology, 12 липня 2023. http://dx.doi.org/10.1093/jleuko/qiad069.

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Abstract Accurately identifying γδ T cells in large single-cell RNA sequencing (scRNA-seq) datasets without additional sc-γδTCR-seq or CITE-seq data remains challenging. In this study, we developed a TCR module scoring strategy for human γδ T cell identification, that is based on modular gene expression of constant and variable TRA/TRB and TRD genes. We evaluated our method using 5’ scRNA-seq datasets comprising both sc-αβTCR-seq and sc-γδTCR-seq as references and demonstrated that it can identify γδ T cells in scRNA-seq datasets with high sensitivity and accuracy. We observed a stable perform
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Davies, Philip, Matt Jones, Juntai Liu, and Daniel Hebenstreit. "Anti-bias training for (sc)RNA-seq: experimental and computational approaches to improve precision." Briefings in Bioinformatics, May 6, 2021. http://dx.doi.org/10.1093/bib/bbab148.

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Abstract RNA-seq, including single cell RNA-seq (scRNA-seq), is plagued by insufficient sensitivity and lack of precision. As a result, the full potential of (sc)RNA-seq is limited. Major factors in this respect are the presence of global bias in most datasets, which affects detection and quantitation of RNA in a length-dependent fashion. In particular, scRNA-seq is affected by technical noise and a high rate of dropouts, where the vast majority of original transcripts is not converted into sequencing reads. We discuss these biases origins and implications, bioinformatics approaches to correct
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Jiang, Ying, Ziyi Chen, Na Han, Jingzhe Shang, and Aiping Wu. "sc-ImmuCC: hierarchical annotation for immune cell types in single-cell RNA-seq." Frontiers in Immunology 14 (July 20, 2023). http://dx.doi.org/10.3389/fimmu.2023.1223471.

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Accurately identifying immune cell types in single-cell RNA-sequencing (scRNA-Seq) data is critical to uncovering immune responses in health or disease conditions. However, the high heterogeneity and sparsity of scRNA-Seq data, as well as the similarity in gene expression among immune cell types, poses a great challenge for accurate identification of immune cell types in scRNA-Seq data. Here, we developed a tool named sc-ImmuCC for hierarchical annotation of immune cell types from scRNA-Seq data, based on the optimized gene sets and ssGSEA algorithm. sc-ImmuCC simulates the natural differentia
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Suphavilai, Chayaporn, Shumei Chia, Ankur Sharma, et al. "Predicting heterogeneity in clone-specific therapeutic vulnerabilities using single-cell transcriptomic signatures." Genome Medicine 13, no. 1 (2021). http://dx.doi.org/10.1186/s13073-021-01000-y.

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AbstractWhile understanding molecular heterogeneity across patients underpins precision oncology, there is increasing appreciation for taking intra-tumor heterogeneity into account. Based on large-scale analysis of cancer omics datasets, we highlight the importance of intra-tumor transcriptomic heterogeneity (ITTH) for predicting clinical outcomes. Leveraging single-cell RNA-seq (scRNA-seq) with a recommender system (CaDRReS-Sc), we show that heterogeneous gene-expression signatures can predict drug response with high accuracy (80%). Using patient-proximal cell lines, we established the validi
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Shi, Fei, Guiyun Zhang, Jinshi Li, et al. "Integrated analysis of single cell‐RNA sequencing and Mendelian randomization identifies lactate dehydrogenase B as a target of melatonin in ischemic stroke." CNS Neuroscience & Therapeutics 30, no. 5 (2024). http://dx.doi.org/10.1111/cns.14741.

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AbstractAimsDespite the success of single‐cell RNA sequencing in identifying cellular heterogeneity in ischemic stroke, clarifying the mechanisms underlying these associations of differently expressed genes remains challenging. Several studies that integrate gene expression and gene expression quantitative trait loci (eQTLs) with genome wide‐association study (GWAS) data to determine their causal role have been proposed.MethodsHere, we combined Mendelian randomization (MR) framework and single cell (sc) RNA sequencing to study how differently expressed genes (DEGs) mediating the effect of gene
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Tirumalasetty, Munichandra Babu, Indrashis Bhattacharya, Mohammad Sarif Mohiuddin, Vijaya Bhaskar Baki, and Mayank Choubey. "Understanding testicular single cell transcriptional atlas: from developmental complications to male infertility." Frontiers in Endocrinology 15 (July 11, 2024). http://dx.doi.org/10.3389/fendo.2024.1394812.

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Spermatogenesis is a multi-step biological process where mitotically active diploid (2n) spermatogonia differentiate into haploid (n) spermatozoa via regulated meiotic programming. The alarming rise in male infertility has become a global concern during the past decade thereby demanding an extensive profiling of testicular gene expression. Advancements in Next-Generation Sequencing (NGS) technologies have revolutionized our empathy towards complex biological events including spermatogenesis. However, despite multiple attempts made in the past to reveal the testicular transcriptional signature(
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Grasso, Cristoforo, Janna E. G. Roet, Catarina Gago de Graça, et al. "Identification and Mapping of Human Lymph Node Stromal Cell Subsets by Combining Single‐Cell RNA Sequencing with Spatial Transcriptomics." European Journal of Immunology 55, no. 6 (2025). https://doi.org/10.1002/eji.202451218.

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ABSTRACTLymph node stromal cells (LNSCs) have a crucial immunomodulatory function, but their heterogeneity in humans is incompletely understood. Here, we report the single‐cell RNA sequencing (scRNA‐seq) of 9267 LNSCs isolated from a human lymph node (LN). This study comprehensively defines the gene signatures of 10 fibroblast subtypes: CCL21+ SC, CCL19+ SC, CD34+CXCL14+ SC, pericytes, DES+ SC, LAMP5+ SC, NR4A1+BCAM+ SC, HLA‐DR+ SC, SEPT4+ SC and GLDN+ SC. The existence of these subtypes was validated across 13 LN donors using 2 publicly available datasets and our dataset. To explore the heter
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Bauer, Tyler, Kevin Mangum, James Shadiow, et al. "Abstract Th0031: The histone deacetylase HDAC11 contributes to diabetic vascular fibrosis." Arteriosclerosis, Thrombosis, and Vascular Biology 45, Suppl_1 (2025). https://doi.org/10.1161/atv.45.suppl_1.th0031.

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The contribution of cardiometabolic disease to atherosclerosis and other cardiovascular pathology is well described, however the mechanisms that control these pathologic changes are unclear. Although the cellular changes contributing to arterial pathology in T2D are more established in endothelial cells and vascular smooth muscle cells, there is less known about the alterations in other cell types, namely fibroblasts. Herein, using unbiased epigenetic arrays and single cell RNA-sequencing (sc-RNA-seq), we define transcriptional differences in fibroblast populations located within the adventiti
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Lall, Snehalika, Abhik Ghosh, Sumanta Ray, and Sanghamitra Bandyopadhyay. "sc-REnF: An entropy guided robust feature selection for single-cell RNA-seq data." Briefings in Bioinformatics 23, no. 2 (2022). http://dx.doi.org/10.1093/bib/bbab517.

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Abstract Annotation of cells in single-cell clustering requires a homogeneous grouping of cell populations. Since single-cell data are susceptible to technical noise, the quality of genes selected prior to clustering is of crucial importance in the preliminary steps of downstream analysis. Therefore, interest in robust gene selection has gained considerable attention in recent years. We introduce sc-REnF [robust entropy based feature (gene) selection method], aiming to leverage the advantages of $R{\prime}{e}nyi$ and $Tsallis$ entropies in gene selection for single cell clustering. Experiments
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Adil, Asif, Vijay Kumar, Arif Tasleem Jan, and Mohammed Asger. "Single-Cell Transcriptomics: Current Methods and Challenges in Data Acquisition and Analysis." Frontiers in Neuroscience 15 (April 22, 2021). http://dx.doi.org/10.3389/fnins.2021.591122.

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Rapid cost drops and advancements in next-generation sequencing have made profiling of cells at individual level a conventional practice in scientific laboratories worldwide. Single-cell transcriptomics [single-cell RNA sequencing (SC-RNA-seq)] has an immense potential of uncovering the novel basis of human life. The well-known heterogeneity of cells at the individual level can be better studied by single-cell transcriptomics. Proper downstream analysis of this data will provide new insights into the scientific communities. However, due to low starting materials, the SC-RNA-seq data face vario
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Cuomo, Anna S. E., Giordano Alvari, Christina B. Azodi, Davis J. McCarthy, and Marc Jan Bonder. "Optimizing expression quantitative trait locus mapping workflows for single-cell studies." Genome Biology 22, no. 1 (2021). http://dx.doi.org/10.1186/s13059-021-02407-x.

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Abstract Background Single-cell RNA sequencing (scRNA-seq) has enabled the unbiased, high-throughput quantification of gene expression specific to cell types and states. With the cost of scRNA-seq decreasing and techniques for sample multiplexing improving, population-scale scRNA-seq, and thus single-cell expression quantitative trait locus (sc-eQTL) mapping, is increasingly feasible. Mapping of sc-eQTL provides additional resolution to study the regulatory role of common genetic variants on gene expression across a plethora of cell types and states and promises to improve our understanding of
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Shen, Yiran, Alexandria Voigt, Xuebing Leng, Amy A. Rodriguez, and Cuong Q. Nguyen. "A current and future perspective on T cell receptor repertoire profiling." Frontiers in Genetics 14 (June 20, 2023). http://dx.doi.org/10.3389/fgene.2023.1159109.

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T cell receptors (TCR) play a vital role in the immune system’s ability to recognize and respond to foreign antigens, relying on the highly polymorphic rearrangement of TCR genes. The recognition of autologous peptides by adaptive immunity may lead to the development and progression of autoimmune diseases. Understanding the specific TCR involved in this process can provide insights into the autoimmune process. RNA-seq (RNA sequencing) is a valuable tool for studying TCR repertoires by providing a comprehensive and quantitative analysis of the RNA transcripts. With the development of RNA techno
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Ruf-Zamojski, Frederique Murielle, Michel A. Zamojski, German Nudelman, et al. "SAT-298 Integrative Single-Cell Transcriptomic and Epigenomic Landscape of Mouse Anterior Pituitary Cell Types." Journal of the Endocrine Society 4, Supplement_1 (2020). http://dx.doi.org/10.1210/jendso/bvaa046.593.

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Abstract The pituitary gland is a critical regulator of the neuroendocrine system. To further our understanding of the classification, cellular heterogeneity, and regulatory landscape of pituitary cell types, we performed and computationally integrated single cell (SC)/single nucleus (SN) resolution experiments capturing RNA expression, chromatin accessibility, and DNA methylation state from mouse dissociated whole pituitaries. Both SC and SN transcriptome analysis and promoter accessibility identified the five classical hormone-producing cell types (somatotropes, gonadotropes (GT), lactotrope
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Xu, Ziye, Tianyu Zhang, Hongyu Chen, et al. "High-throughput single nucleus total RNA sequencing of formalin-fixed paraffin-embedded tissues by snRandom-seq." Nature Communications 14, no. 1 (2023). http://dx.doi.org/10.1038/s41467-023-38409-5.

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AbstractFormalin-fixed paraffin-embedded (FFPE) tissues constitute a vast and valuable patient material bank for clinical history and follow-up data. It is still challenging to achieve single cell/nucleus RNA (sc/snRNA) profile in FFPE tissues. Here, we develop a droplet-based snRNA sequencing technology (snRandom-seq) for FFPE tissues by capturing full-length total RNAs with random primers. snRandom-seq shows a minor doublet rate (0.3%), a much higher RNA coverage, and detects more non-coding RNAs and nascent RNAs, compared with state-of-art high-throughput scRNA-seq technologies. snRandom-se
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Moody, Jonathan, Tsukasa Kouno, Jen-Chien Chang, et al. "SCAFE: a software suite for analysis of transcribed cis-regulatory elements in single cells." Bioinformatics, September 29, 2022. http://dx.doi.org/10.1093/bioinformatics/btac644.

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Abstract Motivation Cell type-specific activities of cis-regulatory elements (CRE) are central to understanding gene regulation and disease predisposition. Single-cell RNA 5’end sequencing (sc-end5-seq) captures the transcription start sites (TSS) which can be used as a proxy to measure the activity of transcribed CREs (tCREs). However, a substantial fraction of TSS identified from sc-end5-seq data may not be genuine due to various artifacts, hindering the use of sc-end5-seq for de novo discovery of tCREs. Results We developed SCAFE—Single Cell Analysis of Five-prime Ends—a software suite that
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Edwards, David M., Philip Davies, and Daniel Hebenstreit. "Synergising single-cell resolution and 4sU labelling boosts inference of transcriptional bursting." Genome Biology 24, no. 1 (2023). http://dx.doi.org/10.1186/s13059-023-02977-y.

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AbstractDespite the recent rise of RNA-seq datasets combining single-cell (sc) resolution with 4-thiouridine (4sU) labelling, analytical methods exploiting their power to dissect transcriptional bursting are lacking. Here, we present a mathematical model and Bayesian inference implementation to facilitate genome-wide joint parameter estimation and confidence quantification (R package: burstMCMC). We demonstrate that, unlike conventional scRNA-seq, 4sU scRNA-seq resolves temporal parameters and furthermore boosts inference of dimensionless parameters via a synergy between single-cell resolution
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