cfDiffusion: diffusion-based efficient generation of high quality scRNA-seq data with classifier-free guidance DOI Creative Commons
Tianjiao Zhang,

Zhongqian Zhao,

Jixiang Ren

et al.

Briefings in Bioinformatics, Journal Year: 2024, Volume and Issue: 26(1)

Published: Nov. 22, 2024

Abstract Single-cell RNA sequencing (scRNA-seq) technology provides a powerful means to measure gene expression at the individual cell level, thereby uncovering intricate cellular heterogeneity that underlies various biological processes, including embryonic development, tumor metastasis, and microbial reproduction. However, variable amounts of data generated across different types within tissues can compromise accuracy downstream analyses. Traditional approaches for generating scRNA-seq simulation often rely on predefined distributions, which negatively impact quality simulated data. Furthermore, these methods typically focus simulating single-attribute cells, necessitating substantial additional multi-attribute lead increased training times. To address limitations, we propose cfDiffusion, novel method grounded in diffusion models incorporates Classifier-Free Guidance high-level feature caching mechanism. By leveraging Guidance, cfDiffusion significantly reduces costs associated with model development compared traditional Classifier methods. The integration mechanism further enhances efficiency by shortening inference While duration remains longer than scDiffusion, it exhibits superior expressiveness single-cell Evaluated datasets from multiple platforms, consistently outperforms state-of-the-art performance metrics. Additionally, enables along pseudo-time scale, facilitating advanced analyses such as tracking differentiation, investigating intercellular communication, elucidating heterogeneity.

Language: Английский

Single cell transcriptome sequencing of stimulated and frozen human peripheral blood mononuclear cells DOI Creative Commons

Céline Derbois,

Marie-Ange Palomares,

Jean‐François Deleuze

et al.

Scientific Data, Journal Year: 2023, Volume and Issue: 10(1)

Published: July 6, 2023

Abstract Peripheral blood mononuclear cells (PBMCs) are that a critical part of the immune system used to fight off infection, defending our bodies from harmful pathogens. In biomedical research, PBMCs commonly study global response disease outbreak and progression, pathogen infections, for vaccine development multitude other clinical applications. Over past few years, revolution in single-cell RNA sequencing (scRNA-seq) has enabled an unbiased quantification gene expression thousands individual cells, which provides more efficient tool decipher human diseases. this work, we generate scRNA-seq data at high depth (>100,000 reads/cell) than 30,000 resting, stimulated, fresh frozen conditions. The generated can be benchmarking batch correction integration methods, effect freezing-thawing cycles on quality cell populations their transcriptomic profiles.

Language: Английский

Citations

11
Elevations in presepsin, PCT, hs-CRP, and IL-6 levels predict mortality among septic patients in the ICU DOI
Yan Zhou,

Yong-wen Feng,

Xiaomin Liang

et al.

Journal of Leukocyte Biology, Journal Year: 2024, Volume and Issue: 116(4), P. 890 - 900

Published: May 22, 2024

Abstract This study aimed to investigate whether changes in presepsin, procalcitonin, high-sensitivity C-reactive protein, and interleukin 6 levels predict mortality septic patients the intensive care unit. enrolled between November 2020 December 2021. Levels of were measured on first (PSEP_0, PCT_0, hsCRP_0, IL-6_0) third days (PSEP_3, PCT_3, hsCRP_3, IL-6_3). Follow-up was performed 3, 7, 14, 21, 28 after enrollment. The outcome all-cause death. included 119 participants, 18.5%. In univariable Cox proportional hazards regression analysis, ΔPSEP (= PSEP_3 – PSEP_0) > 211.49 pg/mL (hazard ratio, 2.70; 95% confidence interval, 1.17–6.22), ΔPCT PCT_3 PCT_0) –0.13 ng/mL 7.31; 2.68–19.80), ΔhsCRP hsCRP_3 hsCRP_0) −19.29 mg/L 6.89; 1.61–29.40), ΔIL-6 IL-6_3 1.00 3.13; 1.35–7.24) indicated an increased risk mortality. composite concordance index for alterations all 4 distinct biomarkers highest (concordance index, 0.83; 0.76–0.91), suggesting optimal performance this panel prediction. decision curve compared with Acute Physiology Chronic Health Evaluation II Sequential (sepsis-related) Organ Failure Assessment scores, combination had a larger net benefit. Interestingly, predominantly produced by monocytes upon lipopolysaccharide stimulation peripheral blood mononuclear cells. ΔPSEP, ΔPCT, ΔhsCRP, are reliable predicting unit, their has best performance.

Language: Английский

Citations

4
CryoSCAPE: Scalable immune profiling using cryopreserved whole blood for multi-omic single cell and functional assays DOI Creative Commons
Alexander T. Heubeck, Cole G. Phalen, N Kaul

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 3, 2025

The field of single cell technologies has rapidly advanced our comprehension the human immune system, offering unprecedented insights into cellular heterogeneity and function. While cryopreserved peripheral blood mononuclear (PBMC) samples enable deep characterization cells, challenges in clinical isolation preservation limit their application underserved communities with limited access to research facilities. We present CryoSCAPE (Cryopreservation for Scalable Cellular And Proteomic Exploration), a scalable method studies PBMC multi-omic assays using direct cryopreservation whole blood. Comparative analyses matched from density gradient demonstrate efficacy this methodology capturing proportions molecular features. was then optimized verified high sample throughput fixed RNA sequencing liquid handling automation batch 60 samples. Additionally, demonstrated be compatible functional assays, enabling research. method, scalability cost-effectiveness, allows high-throughput while minimizing challenges. Utilization clinic potential democratize single-cell enhance understanding function across diverse populations.

Language: Английский

Citations

0
Characterization of the Immune Microenvironment and Identification of Biomarkers in Chronic Rhinosinusitis with Nasal Polyps Using Single-Cell RNA Sequencing and Transcriptome Analysis DOI Creative Commons
Yakun Wang, Xinyu Song, Mulan Jin

et al.

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 253 - 277

Published: Jan. 1, 2024

Purpose: Chronic rhinosinusitis is a prevalent condition in the field of otorhinolaryngology; however, its pathogenesis remains to be elucidated. The immunological defense nasal mucosa significantly influenced by dendritic cells (DCs). We identified specific biological indicators linked DCs and explored their significance cases chronic with polyps (CRSwNP). Patients Methods: categorized using single-cell RNA (scRNA) sequencing, combined transcriptome sequencing was used identify potential candidate genes for CRSwNP. selected three biomarkers based on two algorithms performed enrichment immune correlation analyses. Biomarkers were verified training validation sets, receiver operating characteristic curves, immunohistochemistry, quantitative real-time reverse-transcription PCR (qRT-PCR). Variations biomarker expression validated pseudotime analysis. networks competing transcription factor (TF)-mRNA endogenous (ceRNA) established, protein drugs associated these predicted. Results: Both scRNA-seq data showed that infiltration higher CRSwNP group than control group. Three DC-related (NR4A1, CLEC4G, CD163) identified. In CRSwNP, NR4A1 decreased, whereas CLEC4G CD163 increased. All shown involved metabolic pathways These γδ T cells, effector memory CD4 + regulatory immature DCs. According analysis, decreased from high low, remained low. Conclusion: screened DC-associated progression integrating whole sequencing. analyzed which they involved, molecular mechanisms related drugs, constructed ceRNA, TF-mRNA, biomarker–drug new treatment targets, laying groundwork clinical management Keywords: cell, transcriptomic

Language: Английский

Citations

2
Single‐cell sequencing: Current applications in various tuberculosis specimen types DOI Creative Commons
Yuqin Zeng, Quan Ma, Jinyun Chen

et al.

Cell Proliferation, Journal Year: 2024, Volume and Issue: 57(11)

Published: July 2, 2024

Abstract Tuberculosis (TB) is a chronic disease caused by Mycobacterium tuberculosis ( M.tb ) and responsible for millions of deaths worldwide each year. It has complex pathogenesis that primarily affects the lungs but can also impact systemic organs. In recent years, single‐cell sequencing technology been utilized to characterize composition proportion immune cell subpopulations associated with TB since it high resolution surpasses conventional techniques. This paper reviews current use technologies in research their application analysing specimens from various sources TB, peripheral blood lung specimens. The focus on how these reveal dynamic changes subpopulations, genes proteins during progression after infection. Based findings, significant potential clinical value field research. Next, we will real‐world applications targets identified through diagnostics, therapeutics development effective vaccines.

Language: Английский

Citations

2
Th2 cell clonal expansion at diagnosis in human type 1 diabetes DOI Creative Commons
Aditi Narsale,

Francisco Almanza,

Theo Tran

et al.

Clinical Immunology, Journal Year: 2023, Volume and Issue: 257, P. 109829 - 109829

Published: Oct. 29, 2023

Soon after diagnosis with type 1 diabetes (T1D), many patients experience a period of partial remission. A longer remission is associated better response to treatment, but the mechanism not known. The frequency CD4

Language: Английский

Citations

5
CryoSCAPE: Scalable Immune Profiling Using Cryopreserved Whole Blood for Multi-omic Single Cell and Functional Assays DOI Creative Commons
Alexander T. Heubeck, Cole G. Phalen, N Kaul

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 21, 2024

Abstract Background The field of single cell technologies has rapidly advanced our comprehension the human immune system, offering unprecedented insights into cellular heterogeneity and function. While cryopreserved peripheral blood mononuclear (PBMC) samples enable deep characterization cells, challenges in clinical isolation preservation limit their application underserved communities with limited access to research facilities. We present CryoSCAPE (Cryopreservation for Scalable Cellular And Proteomic Exploration), a scalable method studies PBMC multi-omic assays using direct cryopreservation whole blood. Results Comparative analyses matched from density gradient demonstrate efficacy this methodology capturing proportions molecular features. was then optimized verified high sample throughput fixed RNA sequencing liquid handling automation batch 60 samples. Additionally, demonstrated be compatible functional assays, enabling research. Conclusions method, scalability cost-effectiveness, allows high-throughput while minimizing challenges. Utilization clinic potential democratize single-cell enhance understanding function across diverse populations.

Language: Английский

Citations

1
Comparative proteomic profiling of the ovine and human PBMC inflammatory response DOI Creative Commons
Ahmed N. ELKhamary,

Iris Gerner,

Andrea Bileck

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: June 28, 2024

Abstract Understanding the cellular and molecular mechanisms of inflammation requires robust animal models. Sheep are commonly used in immune-related studies, yet validity sheep as models for immune inflammatory diseases remains to be established. This cross-species comparative study analyzed vitro response ovine (oPBMCs) human PBMCs (hPBMCs) using mass spectrometry, profiling proteome secretome whole cell lysate. Of entire lysate (oPBMCs: 4217, hPBMCs: 4574 proteins) 47.8% 1913, 1375 32.8% were orthologous between species, among them 32 CD antigens, indicating presence six subsets. Following stimulation, 71 proteins oPBMCs 176 hPBMCs showed differential abundance, with only 7 overlapping. Network Gene Ontology analyses identified 16 shared inflammatory-related terms 17 canonical pathways similar activation/inhibition patterns both demonstrating significant conservation specific responses. However, PMBCs also contained a unique WC1 + γδ T-cell subset, not detected hPBMCs. Furthermore, differences trends seven sets DAPs humans, emphasize need consider interspecies translational studies research.

Language: Английский

Citations

0
Single-cell RNA-sequencing reveals a profound immune cell response in human cytomegalovirus-infected humanized mice DOI Creative Commons
An Wang,

Xiao-Xu Zhu,

Yuanyuan Bie

et al.

Virologica Sinica, Journal Year: 2024, Volume and Issue: 39(5), P. 782 - 792

Published: Aug. 15, 2024

Human cytomegalovirus (HCMV) is a common herpesvirus that persistently infects large portion of the world's population. Despite robust host immune response, HCMV able to replicate, evade defenses, and establish latency throughout lifespan by developing multiple immunomodulatory strategies, making studies on interaction between infection response particularly important. has strict specificity specifically humans. Therefore, most in vivo researches rely clinical samples. Fortunately, establishment humanized mouse models allows for convenient in-lab animal experiments involving infection. Single-cell RNA sequencing enables study relationship viral gene expressions at single-cell level within cells. In this study, we assessed expression alterations PBMCs HCMV-infected mice, which sheds light onto virus-host interactions context mice provides valuable dataset related researches.

Language: Английский

Citations

0
Shared and unique patterns of autonomous human endogenous retrovirus loci transcriptomes in CD14 + monocytes from individuals with physical trauma or infection with COVID-19 DOI Creative Commons
Hyunmin Koo, Casey D. Morrow

Retrovirology, Journal Year: 2024, Volume and Issue: 21(1)

Published: Nov. 4, 2024

Abstract Since previous studies have suggested that the RNAs of human endogenous retrovirus (HERV) might be involved in regulating innate immunity, it is important to investigate HERV transcriptome patterns immune cell types such as CD14 + monocytes. Using single RNA-seq datasets from resting or stimulated PBMCs mapped 3,220 known discrete autonomous proviral loci, we found individual-specific variation transcriptomes between loci Analysis paired same individual were cultured vitro with LPS without (i.e. control) revealed 36 monocytes detected only after activation. To extend our analysis vivo activated monocytes, used two scRNA-seq had demonstrated activation circulating patients physical trauma hospitalized COVID-19 infections. For direct comparison and datasets, first analyzed 1.625 billion sequence reads a composite pangenome control 21 normal individuals. Comparison read depth samples 39 11 significantly different (Mann-Whitney U test), 9 shared datasets. The capacity compare cells, like across pathological conditions will lead greater understanding physiological role expression health disease.

Language: Английский

Citations

0