arXiv:2409.07594cs.LGstat.ML2024-09被引 9

从图像等非结构化数据中自动发现基因扰动间的因果交互关系。

Automated Discovery of Pairwise Interactions from Unstructured Data

  • 基于成对干预设计两种交互检测方法,适用于隐变量扰动。
  • 在50对基因敲除实验中,识别出比随机搜索多的已知生物互作。
  • 可直接处理图像等非结构化数据,适合低成本实验场景。

系统中扰动之间的成对交互能揭示底层机制的因果依赖关系。当观测为低维手工测量时,检测交互可通过简单统计检验实现,但难以检测影响潜在变量的扰动间交互。本文推导了两种基于成对干预的交互检验方法,并将其集成到主动学习流程中,高效发现扰动间的成对交互。在生物学背景下,成对扰动实验常用于揭示单个扰动无法观察到的相互作用。我们的方法可直接应用于图像像素等非结构化数据,拓展了传统细胞存活率实验的交互定义,且适用于成本更低的实验。在多个合成与真实生物实验中验证,该方法能有效识别交互对。在一项真实实验中,我们敲除了50对基因并用显微镜图像测量效果,结果表明,相比随机搜索和标准主动学习基线,本方法能显著恢复更多已知生物互作。

原文摘要 · Abstract (English)

Pairwise interactions between perturbations to a system can provide evidence for the causal dependencies of the underlying underlying mechanisms of a system. When observations are low dimensional, hand crafted measurements, detecting interactions amounts to simple statistical tests, but it is not obvious how to detect interactions between perturbations affecting latent variables. We derive two interaction tests that are based on pairwise interventions, and show how these tests can be integrated into an active learning pipeline to efficiently discover pairwise interactions between perturbations. We illustrate the value of these tests in the context of biology, where pairwise perturbation experiments are frequently used to reveal interactions that are not observable from any single perturbation. Our tests can be run on unstructured data, such as the pixels in an image, which enables a more general notion of interaction than typical cell viability experiments, and can be run on cheaper experimental assays. We validate on several synthetic and real biological experiments that our tests are able to identify interacting pairs effectively. We evaluate our approach on a real biological experiment where we knocked out 50 pairs of genes and measured the effect with microscopy images. We show that we are able to recover significantly more known biological interactions than random search and standard active learning baselines.

因果发现生物信息学主动学习图像分析

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