ArticleNature communications2025
ALFA-K: Local adaptive mapping of karyotype fitness landscapes.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Ploidy shapes gemcitabine response through altered potency and delayed cell death.bioRxiv : the preprint server for biology · 2026Article
- Cancer Evolvability Determines Therapy Outcomes.bioRxiv : the preprint server for biology · 2026Article
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Abstract
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.
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