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三百万张经过化学和遗传扰动处理的细胞的图像和形态特征图谱。

Three million images and morphological profiles of cells treated with matched chemical and genetic perturbations.

机构信息

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Merck Healthcare KGaA, Darmstadt, Germany.

出版信息

Nat Methods. 2024 Jun;21(6):1114-1121. doi: 10.1038/s41592-024-02241-6. Epub 2024 Apr 9.

Abstract

The identification of genetic and chemical perturbations with similar impacts on cell morphology can elucidate compounds' mechanisms of action or novel regulators of genetic pathways. Research on methods for identifying such similarities has lagged due to a lack of carefully designed and well-annotated image sets of cells treated with chemical and genetic perturbations. Here we create such a Resource dataset, CPJUMP1, in which each perturbed gene's product is a known target of at least two chemical compounds in the dataset. We systematically explore the directionality of correlations among perturbations that target the same protein encoded by a given gene, and we find that identifying matches between chemical and genetic perturbations is a challenging task. Our dataset and baseline analyses provide a benchmark for evaluating methods that measure perturbation similarities and impact, and more generally, learn effective representations of cellular state from microscopy images. Such advancements would accelerate the applications of image-based profiling of cellular states, such as uncovering drug mode of action or probing functional genomics.

摘要

具有相似细胞形态影响的遗传和化学干扰的鉴定,可以阐明化合物的作用机制或遗传途径的新调节剂。由于缺乏经过精心设计和充分注释的用化学和遗传干扰处理的细胞图像集,用于识别此类相似性的研究方法一直滞后。在这里,我们创建了这样一个资源数据集 CPJUMP1,其中每个受干扰基因的产物至少是该数据集中两种化学化合物的已知靶点。我们系统地探索了针对给定基因编码的同一蛋白质的干扰之间相关性的方向性,并且我们发现,鉴定化学和遗传干扰之间的匹配是一项具有挑战性的任务。我们的数据集和基准分析为评估测量干扰相似性和影响的方法提供了基准,更普遍地说,从显微镜图像中学习细胞状态的有效表示。此类进步将加速基于图像的细胞状态分析的应用,例如揭示药物作用模式或探测功能基因组学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3732/11166567/ad32b1d8979a/41592_2024_2241_Fig1_HTML.jpg

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