Longitudinal single-cell data informs deterministic modelling of inflammatory bowel disease

Area of Science:

• Immunology
• Computational Biology
• Systems Biology

Background:

• Single-cell technologies like flow cytometry and single-cell mRNA sequencing (scRNA-seq) provide detailed cellular and molecular profiles.
• These methods offer a snapshot in time, limiting the understanding of dynamic biological processes.
• Immune system dynamics are complex and crucial for understanding diseases like inflammatory bowel disease (IBD).

Purpose of the Study:

• To explore the utility of longitudinal single-cell data for deterministic ordinary differential equation (ODE)-based modeling of immune dynamics.
• To mechanistically describe immune cell population changes during IBD using mathematical modeling.
• To validate model predictions and assess translational relevance in human IBD patients.

Main Methods:

• Utilized longitudinal flow cytometry and scRNA-seq data from murine colitis models to derive ODE-based models of colonic cell type dynamics.
• Validated predicted cellular turnover rates using KI-67 staining and independent scRNA-seq gene expression data.
• Applied deconvolution of longitudinal bulk mRNA sequencing data from human IBD patients treated with olamkicept.

Main Results:

• Developed an ODE-based mathematical model that accurately described longitudinal changes in colonic cell numbers during murine colitis.
• The model demonstrated generalizability across different experimental protocols and techniques.
• Model parameter estimations for cellular turnover rates were validated, and neutrophil depletion was identified as a potential contributor to remission in human IBD patients.

Conclusions:

• Longitudinal single-cell data, when integrated with ODE-based modeling, can mechanistically elucidate immune dynamics.
• The developed mathematical model shows predictive power and potential for understanding immune responses in health and disease.
• This approach offers a promising avenue for identifying therapeutic strategies, such as targeting neutrophil populations, for IBD treatment.