Ontology highlight
ABSTRACT:
PROVIDER: PRJNA741605 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15002534.fastq.gz | Fastqsanger.gz | |||
| SRR15002535.fastq.gz | Fastqsanger.gz | |||
| SRR15002536.fastq.gz | Fastqsanger.gz | |||
| SRR15002537.fastq.gz | Fastqsanger.gz | |||
| SRR15002538.fastq.gz | Fastqsanger.gz |
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Project description:Kilian2024 - Immune cell dynamics in Cue-Induced Extended Human Colitis Model
Single-cell technologies such as scRNA-seq and flow cytometry provide critical insights into immune cell behavior in inflammatory bowel disease (IBD). However, integrating these datasets into computational models for dynamic analysis remains challenging. Here, Kilian et al., (2024) developed a deterministic ODE-based model that incorporates these technologies to study immune cell population changes in murine colitis. The model parameters were optimized to fit experimental data, ensuring an accurate representation of immune cell behavior over time. It was then validated by comparing simulations with experimental data using Pearson’s correlation and further tested on independent datasets to confirm its robustness. Additionally, the model was applied to clinical bulk RNA-seq data from human IBD patients, providing valuable insights into immune system dynamics and potential therapeutic strategies.
Figure 4c, obtained from the simulation of human colitis model is highlighted here.
This model is described in the article:
Kilian, C., Ulrich, H., Zouboulis, V.A. et al. Longitudinal single-cell data informs deterministic modelling of inflammatory bowel disease. npj Syst Biol Appl 10, 69 (2024). https://doi.org/10.1038/s41540-024-00395-9
Abstract:
Single-cell-based methods such as flow cytometry or single-cell mRNA sequencing (scRNA-seq) allow deep molecular and cellular profiling of immunological processes. Despite their high throughput, however, these measurements represent only a snapshot in time. Here, we explore how longitudinal single-cell-based datasets can be used for deterministic ordinary differential equation (ODE)-based modelling to mechanistically describe immune dynamics. We derived longitudinal changes in cell numbers of colonic cell types during inflammatory bowel disease (IBD) from flow cytometry and scRNA-seq data of murine colitis using ODE-based models. Our mathematical model generalised well across different protocols and experimental techniques, and we hypothesised that the estimated model parameters reflect biological processes. We validated this prediction of cellular turnover rates with KI-67 staining and with gene expression information from the scRNA-seq data not used for model fitting. Finally, we tested the translational relevance of the mathematical model by deconvolution of longitudinal bulk mRNA-sequencing data from a cohort of human IBD patients treated with olamkicept. We found that neutrophil depletion may contribute to IBD patients entering remission. The predictive power of IBD deterministic modelling highlights its potential to advance our understanding of immune dynamics in health and disease.
This model was curated during the Hackathon hosted by BioMed X GmbH in 2024.
2025-03-07 | MODEL2502180001 | BioModels
Project description:We aim to study the gene alteration in diabetic failing heart and decipher the molecular mechanisms underlying diabetes-associated heart failure. Diabetic patients are more vulnerable to cardiac dysfunction. The pathogenesis of diabetes-associated heart failure is multiple, including cardiac pathological remodeling, intracellular metabolic disorders, cardiac inflammation, etc. To determine which signaling pathways causes the myocardial alterations, we plan to identify the individual gene function during the pathogenesis using an unbiased large-scale screening. Firstly, gene expression should be assessed. RNA-seq is used to detect gene changes, afterwards, the potential candidates involved in the molecular basis induing diabetic heart failure will be validated by other assessment and function study will be performed to explore their role in the onset and progression of heart failure in diabetes. Samples are healthy subject versus those with diabetes with cardiovascular disease (CVD) and heart failure (HF)
2026-08-14 | E-MTAB-16712 | biostudies-arrayexpress
Project description:<p>BACKGROUND: Imbalances in cardiac branched-chain amino acid (BCAA) metabolism and mitochondrial homeostasis are implicated in the onset and development of heart failure. However, the mechanisms triggering the downregulation of cardiac BCAA metabolism in heart failure remain unclear. Here, we identify a novel role of RNA-binding protein GRSF1 (guanine-rich RNA sequence binding factor 1) in post-transcriptionally regulating cell-intrinsic BCAA metabolic pathways, ultimately contributing to the pathogenesis of heart failure.</p><p>METHODS: We examined GRSF1 expression in the heart tissues of patients with dilated cardiomyopathy and generated mice with cardiomyocyte-specific deletion or overexpression of GRSF1 in vivo to investigate its role in heart failure. The effect of GRSF1 on BCAA homeostasis was assessed through untargeted and targeted metabolomics and mitochondrial function analysis. To elucidate the mechanisms underlying GRSF1-mediated metabolic regulation, we employed mice with cardiomyocyte-specific deletion of BCKDHB, and mice with cardiomyocyte-specific expression of GRSF1 lacking a quasi-RNA recognition motif. </p><p>RESULTS: GRSF1 expression was significantly decreased in the hearts of patients with heart failure and failing murine hearts. Cardiomyocyte-specific GRSF1 deletion resulted in cardiac dysfunction, spontaneous progression to dilated cardiomyopathy, and heart failure, accompanied by increased cardiac hypertrophy and fibrosis. Conversely, GRSF1 overexpression attenuated cardiac remodeling and heart failure induced by transverse aortic constriction. Mechanistically, GRSF1 maintained BCAA homeostasis and mitochondrial function by directly interacting with the G-tracts in coding region of BCKDHB mRNA through a quasi-RNA recognition motif to promote the stability of BCKDHB mRNA at the post-transcriptional level, thereby increasing its protein expression. Functional recovery mediated by GRSF1 overexpression in cardiomyocytes was partially blocked upon cardiac-specific deletion of BCKDHB. </p><p>CONCLUSIONS: Our study identified GRSF1 as a cell-intrinsic metabolic checkpoint that maintains cardiac BCAA homeostasis by regulating BCKDHB mRNA turnover. Targeting GRSF1 may offer therapeutic benefits for heart failure and other cardiometabolic diseases requiring BCAA manipulation.</p>
2025-10-19 | MTBLS13178 | MetaboLights
Project description:We aim to study the gene alteration in diabetic failing heart and decipher the molecular mechanisms underlying diabetes-associated heart failure. Diabetic patients are more vulnerable to cardiac dysfunction. The pathogenesis of diabetes-associated heart failure is multiple, including cardiac pathological remodeling, intracellular metabolic disorders, cardiac inflammation, etc. To determine which signaling pathways causes the myocardial alterations, we plan to identify the individual gene function during the pathogenesis using an unbiased large-scale screening. Firstly, gene expression should be assessed. RNA-seq is used to detect gene changes, afterwards, the potential candidates involved in the molecular basis induing diabetic heart failure will be validated by other assessment and function study will be performed to explore their role in the onset and progression of heart failure in diabetes.
2026-02-20 | E-MTAB-16575 | biostudies-arrayexpress
Project description:Heart failure is a multisystem syndrome caused by structural and functional defects in multiple tissues. The study aims to identify differentially regulated genes in skeletal muscle of heart failure patients. Here, we obtained biopsies from the pectoralis major muscle and performed RNA sequencing to profile the gene expression patterns from six heart failure patients and three healthy controls.
2020-09-07 | E-MTAB-8531 | biostudies-arrayexpress
Project description:Human white blood cells from healthy, heart failure risk patients, asymptomatic left ventricular dysfunction patients, chronic heart failure, acute heart failure patients Common reference experiment, 9 replicates per group.
2012-05-02 | E-GEOD-21125 | biostudies-arrayexpress
Project description:This data represents whole transcriptome total RNA gene expression profiles of peripheral blood mononuclear cells collected from 29 advanced heart failure patients on the day before undergoing mechanical circulatory support surgery. Keywords = Advanced Heart Failure. Keywords = Mechanical Circulatory Support. Keywords = Biological Age. Keywords = PBMC. Keywords = Immune Response. Keywords = Peripheral Blood. Keywords =Organ Function. Keywords = Recovery. Organism: Homo sapiens. Type: Expression profiling by array. Platforms: Illumina HiSeq 2500.
2018-02-13 | GSE104423 | GEO