纵向单细胞数据为炎症性肠病的确定性建模提供了信息。

IF 3.5 2区 生物学 Q1 MATHEMATICAL & COMPUTATIONAL BIOLOGY
Christoph Kilian, Hanna Ulrich, Viktor A Zouboulis, Paulina Sprezyna, Jasmin Schreiber, Tomer Landsberger, Maren Büttner, Moshe Biton, Eduardo J Villablanca, Samuel Huber, Lorenz Adlung
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引用次数: 0

摘要

流式细胞仪或单细胞 mRNA 测序(scRNA-seq)等基于单细胞的方法可对免疫过程进行深入的分子和细胞分析。然而,尽管这些方法具有高通量,但其测量结果仅代表时间快照。在这里,我们探讨了如何将基于单细胞的纵向数据集用于基于确定性常微分方程(ODE)的建模,从机理上描述免疫动态。我们利用基于 ODE 的模型,从小鼠结肠炎的流式细胞术和 scRNA-seq 数据中得出了炎症性肠病(IBD)期间结肠细胞类型的细胞数量纵向变化。我们的数学模型在不同的方案和实验技术中具有良好的通用性,我们假设估计的模型参数反映了生物过程。我们用 KI-67 染色法和未用于模型拟合的 scRNA-seq 数据中的基因表达信息验证了对细胞周转率的预测。最后,我们通过对一组接受奥兰凯西普治疗的人类 IBD 患者的纵向大量 mRNA 序列数据进行解卷积,检验了数学模型的转化相关性。我们发现,中性粒细胞耗竭可能有助于 IBD 患者进入缓解期。IBD 确定性建模的预测能力凸显了它在促进我们对健康和疾病中免疫动态的理解方面的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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

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.

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来源期刊
NPJ Systems Biology and Applications
NPJ Systems Biology and Applications Mathematics-Applied Mathematics
CiteScore
5.80
自引率
0.00%
发文量
46
审稿时长
8 weeks
期刊介绍: npj Systems Biology and Applications is an online Open Access journal dedicated to publishing the premier research that takes a systems-oriented approach. The journal aims to provide a forum for the presentation of articles that help define this nascent field, as well as those that apply the advances to wider fields. We encourage studies that integrate, or aid the integration of, data, analyses and insight from molecules to organisms and broader systems. Important areas of interest include not only fundamental biological systems and drug discovery, but also applications to health, medical practice and implementation, big data, biotechnology, food science, human behaviour, broader biological systems and industrial applications of systems biology. We encourage all approaches, including network biology, application of control theory to biological systems, computational modelling and analysis, comprehensive and/or high-content measurements, theoretical, analytical and computational studies of system-level properties of biological systems and computational/software/data platforms enabling such studies.
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