Yang Jingjie, Fang Heidi, Dhesi Jagdeep, Yoon Iris H R, Bull Joshua A, Byrne Helen M, Harrington Heather A, Grindstaff Gillian
Mathematical Institute, University of Oxford, Oxford, OX2 6GG, UK.
Wesleyan University, Middletown, CT, 06459, USA.
J Math Biol. 2025 Aug 5;91(3):25. doi: 10.1007/s00285-025-02253-6.
The complex and dynamic crosstalk between tumour and immune cells results in tumours that can exhibit distinct qualitative behaviours-elimination, equilibrium, and escape-and intricate spatial patterns, yet share similar cell configurations in the early stages. We offer a topological approach to analyse time series of spatial data of cell locations (including tumour cells and macrophages) in order to predict malignant behaviour. We propose four topological vectorisations specialised to such cell data: persistence images of Vietoris-Rips and radial filtrations at static time points, and persistence images for zigzag filtrations and persistence vineyards varying in time. To demonstrate the approach, synthetic data are generated from an agent-based model with varying parameters. We compare the performance of topological summaries in predicting-with logistic regression at various time steps-whether tumour niches surrounding blood vessels are present at the end of the simulation, as a proxy for metastasis (i.e., tumour escape). We find that both static and time-dependent methods accurately identify perivascular niche formation, significantly earlier than simpler markers such as the number of tumour cells and the macrophage phenotype ratio. We find additionally that dimension 0 persistence applied to macrophage data, representing multi-scale clusters of the spatial arrangement of macrophages, performs best at this classification task at early time steps, prior to full tumour development, and performs even better when time-dependent data are included; in contrast, topological measures capturing the shape of the tumour, such as tortuosity and punctures in the cell arrangement, perform best at intermediate and later stages. We analyse the logistic regression coefficients for each method to identify detailed shape differences between the classes.
肿瘤细胞与免疫细胞之间复杂且动态的相互作用,导致肿瘤呈现出不同的定性行为(消除、平衡和逃逸)以及复杂的空间模式,不过在早期阶段它们具有相似的细胞结构。我们提供一种拓扑学方法,用于分析细胞位置(包括肿瘤细胞和巨噬细胞)的空间数据的时间序列,以预测恶性行为。我们提出了四种专门针对此类细胞数据的拓扑矢量化方法:静态时间点的Vietoris-Rips持久图像和径向过滤,以及随时间变化的之字形过滤的持久图像和持久葡萄园。为了演示该方法,我们从一个具有可变参数的基于主体的模型生成了合成数据。我们在不同时间步长使用逻辑回归比较拓扑摘要在预测模拟结束时血管周围是否存在肿瘤微环境方面的性能,以此作为转移(即肿瘤逃逸)的指标。我们发现,静态和时间相关方法都能准确识别血管周围微环境的形成,比诸如肿瘤细胞数量和巨噬细胞表型比例等更简单的标志物要早得多。我们还发现,应用于巨噬细胞数据的0维持久性,代表巨噬细胞空间排列的多尺度簇,在肿瘤完全发展之前的早期时间步长,在此分类任务中表现最佳,当纳入时间相关数据时表现甚至更好;相比之下,捕捉肿瘤形状的拓扑测量,如细胞排列中的曲折度和穿孔,在中期和后期表现最佳。我们分析了每种方法的逻辑回归系数,以识别不同类别之间的详细形状差异。