从谱系上下文学习发育动力学
Learning developmental dynamics from lineage context
Gokul Gowri, Nic Fishman, William N. Colgan, Minming Wang, Yusuke Kijima, Sachin A. Kumar, Aleksandr Zimin, Luke W. Koblan 等 13 位作者
AI 速览：作者提出“谱系修补”（lineage inpainting）生成建模方法，利用树结构Transformer与随机插值从谱系上下文预测细胞状态动态。
A central goal of biology is to predict the dynamics of multicellular systems. Lineage context (the states of a cell's sisters, cousins, etc.) could inform these predictions, but how best to leverage it remains unclear. Here we introduce lineage inpainting, a generative modeling approach that uses lineage context with tree-structured transformers and stochastic interpolants to model cell state dynamics across lineage trees. Applied to a lineage-traced transcriptional atlas of mouse embryogenesis, it recovers dynamics not resolved by gene expression alone, including multiple transcriptional convergence events where distinct lineages are drawn to a common state. Despite being fit on unperturbed development, lineage inpainting can generate hypotheses about perturbation responses by simulating counterfactuals. These simulations agree in many cases with observed developmental phenotypes, including a single-cell measurement of the Tbx5 knockout response. Our results show that lineage information provides a rich source of context for learning multicellular dynamics.