Ontology highlight
ABSTRACT:
PROVIDER: PRJNA668853 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12816600.fastq.gz | Fastqsanger.gz | |||
| SRR12816601.fastq.gz | Fastqsanger.gz | |||
| SRR12816602.fastq.gz | Fastqsanger.gz | |||
| SRR12816603.fastq.gz | Fastqsanger.gz | |||
| SRR12816604.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.
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2024-04-29 | E-MTAB-13526 | biostudies-arrayexpress
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Project description:Lack of a standard method for stratifying advanced-stage NSCLC patients receiving platinum combination therapy often results in a number of patients that do not derive benefit yet are still exposed to treatment toxicity. We hypothesized that miRNAs in pre-treatment serum and/or plasma could be used to differentiate non-small cell lung cancer (NSCLC) patients who would have disease progression to first-line carboplatin and gemcitabine chemotherapy at first response assessment. miRNA profiling of mature and precursor miRNAs was performed on total RNA isolated from the pre-treatment serum and plasma of 24 NSCLC patients. Single validated candidates or combinations thereof were selected based on specificity and sensitivity to segregate patients with disease progression at first radiologic response (PD) vs. those without progressed disease (nonPD). Two precursor miRNA were significantly over-expressed in serum (but not plasma) of PD patients: pre-miR-518b and pre-miR-598. Serum miRNAs may serve as a screening tool in predicting chemoresistance to platinum-based combination chemotherapy. miRNA microarray was performed on RNA extracted from matched human serum or plasma obtained from NSCLC patients
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