肿瘤生死模型中生长模式的分支时间特征
Branching-Time Signatures of Growth Regime in Tumor Birth-Death Models
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中文总结 AI 辅助
研究肿瘤生死模型中生长模式与内部分支时间分布的关系，通过连续时间生死模型研究发现指数增长种群分支时间单峰，逻辑斯蒂增长有复杂谱系结构及阶段转变，模拟结果支持了理论发现。
中文摘要 AI 辅助
肿瘤进化受细胞分裂、死亡、竞争及局部微环境限制影响。因这些动态通常无法直接观测，从肿瘤细胞样本的体细胞变异推断的系统发育树可间接记录产生样本的种群历史。本文研究推断的内部分支时间分布是否呈现依赖于潜在肿瘤生长模式的特征。具体研究肿瘤进化连续时间生死模型中内部分支时间的分布。指数增长种群的内部分支时间呈单峰分布，峰位靠近根部。相比之下，受承载能力限制的逻辑斯蒂增长产生更复杂的谱系结构：随着肿瘤起始后时间增加，分支时间分布经历系统转变，从扩张主导阶段，经中间的早期-近期双峰阶段，到最终的近期主导阶段。对重建肿瘤谱系的广泛模拟支持了这些理论发现。
英文摘要
Tumor evolution is shaped by cell division, cell death, competition, and constraints imposed by the local microenvironment. Because these dynamics are usually not observed directly, phylogenetic trees inferred from somatic variation in sampled tumor cells can provide an indirect record of the population history that produced the sample. In this paper, we examine whether the distribution of inferred internal branching times exhibits signatures that depend on the underlying tumor growth regime. Specifically, we study the distribution of internal branching times in continuous-time birth-death models of tumor evolution. Exponentially growing populations exhibit a unimodal distribution of internal branching times, with the mode located near the root. In contrast, logistic growth, which models expansion constrained by carrying capacity, yields a substantially more intricate genealogical structure: the distribution of branching times undergoes a systematic transition as the time elapsed since tumor initiation increases. Specifically, this progression shifts from an expansion-dominated phase, through an intermediate early-recent bimodal phase, to a final recent-dominated phase. Extensive simulations of reconstructed tumor genealogies support these theoretical findings.
