论文标题

在单细胞分辨率下预测细胞对新型药物扰动的反应

Predicting Cellular Responses to Novel Drug Perturbations at a Single-Cell Resolution

论文作者

Hetzel, Leon, Böhm, Simon, Kilbertus, Niki, Günnemann, Stephan, Lotfollahi, Mohammad, Theis, Fabian

论文摘要

单细胞转录组学能够研究单个细胞分辨率下的细胞异质性。但是,由于技术局限性,对许多药物的细胞反应进行测量的高通量筛选(HTSS)仍然是一个挑战,更重要的是,此类多重实验的成本。因此,需要从常规执行的大量RNA HTS中传输信息才能有意义地丰富单细胞数据。我们介绍了一种新的编码器架构ChemCPA,以研究看不见的药物的扰动作用。我们将模型与用于转移学习的体系结构手术结合在一起,并证明对现有的大量RNA HTS数据集进行培训如何可以改善概括性能。更好的概括减少了单细胞分辨率的广泛且昂贵的屏幕的需求。我们设想我们提出的方法将通过其产生内部假设的能力来促进更有效的实验设计,最终加速药物发现。

Single-cell transcriptomics enabled the study of cellular heterogeneity in response to perturbations at the resolution of individual cells. However, scaling high-throughput screens (HTSs) to measure cellular responses for many drugs remains a challenge due to technical limitations and, more importantly, the cost of such multiplexed experiments. Thus, transferring information from routinely performed bulk RNA HTS is required to enrich single-cell data meaningfully. We introduce chemCPA, a new encoder-decoder architecture to study the perturbational effects of unseen drugs. We combine the model with an architecture surgery for transfer learning and demonstrate how training on existing bulk RNA HTS datasets can improve generalisation performance. Better generalisation reduces the need for extensive and costly screens at single-cell resolution. We envision that our proposed method will facilitate more efficient experiment designs through its ability to generate in-silico hypotheses, ultimately accelerating drug discovery.

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