Scholarlink

<p>Despite its critical role in tumor evolution, a detailed quantitative understanding of the evolutionary dynamics of aneuploidy remains elusive. Here we introduce ALFA-K (Adaptive Local Fitness landscapes for Aneuploid Karyotypes), a method that infers chromosome-level karyotype fitness landscapes from longitudinal single-cell data. ALFA-K estimates fitness of thousands of karyotypes closely related to observed populations, enabling robust prediction of emergent karyotypes not yet experimentally detected. We validate ALFA-K’s performance using synthetic data from an agent-based model and empirical data from in vitro and in vivo passaged cell lines. Analysis of fitted landscapes suggests several key insights: (1) Whole genome doubling facilitates aneuploidy evolution by narrowing the spectrum of deleterious copy-number changes; (2) Environmental context and cisplatin treatment significantly modulate the fitness impact of these changes; (3) Fitness effects of copy-number changes depend on parental karyotype; and (4) Chromosome mis-segregation rates strongly influence the predominant karyotypes in evolving populations.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

ALFA-K: Local adaptive mapping of karyotype fitness landscapes

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月27日

查看全文
  • Richard J. Beck,
  • Tao Li,
  • Noemi Andor

摘要

Despite its critical role in tumor evolution, a detailed quantitative understanding of the evolutionary dynamics of aneuploidy remains elusive. Here we introduce ALFA-K (Adaptive Local Fitness landscapes for Aneuploid Karyotypes), a method that infers chromosome-level karyotype fitness landscapes from longitudinal single-cell data. ALFA-K estimates fitness of thousands of karyotypes closely related to observed populations, enabling robust prediction of emergent karyotypes not yet experimentally detected. We validate ALFA-K’s performance using synthetic data from an agent-based model and empirical data from in vitro and in vivo passaged cell lines. Analysis of fitted landscapes suggests several key insights: (1) Whole genome doubling facilitates aneuploidy evolution by narrowing the spectrum of deleterious copy-number changes; (2) Environmental context and cisplatin treatment significantly modulate the fitness impact of these changes; (3) Fitness effects of copy-number changes depend on parental karyotype; and (4) Chromosome mis-segregation rates strongly influence the predominant karyotypes in evolving populations.