Clustering phenotype populations by genome-wide RNAi and multiparametric imaging.
Clustering phenotype populations by genome-wide RNAi and multiparametric imaging.
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DOI：
10.1038/msb.2010.25
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发表时间：
2010-06-08
影响因子：
9.9
通讯作者：
中科院分区：
文献类型：
--
作者：
表型相似性的遗传筛选为基因与生物过程的关联做出了关键贡献。利用RNA干扰（RNAi），细胞中功能丧失效应的高度平行表型分析已变得可行。然而，目前的挑战之一是视觉表型的计算分类和生物功能和过程的预测。在这项研究中，我们描述了一种结合计算和实验的方法来发现新的基因功能和探索功能关系。我们在人类细胞中进行了全基因组RNAi筛选，并使用来自高通量成像的定量描述符来生成多参数表型谱。我们发现，配置文件预测功能的基因表型相似性。具体来说，我们研究了几个候选人，包括在很大程度上未表征的基因DONSON，它与已知的DNA损伤反应（DDR）和基因组完整性的因素共享表型相似性。实验证据支持DONSON是DDR信号传导和基因组完整性所需的新型中心体蛋白。通过自动成像和计算注释的多参数表型分析是功能发现和绘制对细胞扰动的表型反应景观的有力方法。
Genetic screens for phenotypic similarity have made key contributions to associating genes with biological processes. With RNA interference (RNAi), highly parallel phenotyping of loss-of-function effects in cells has become feasible. One of the current challenges however is the computational categorization of visual phenotypes and the prediction of biological function and processes. In this study, we describe a combined computational and experimental approach to discover novel gene functions and explore functional relationships. We performed a genome-wide RNAi screen in human cells and used quantitative descriptors derived from high-throughput imaging to generate multiparametric phenotypic profiles. We show that profiles predicted functions of genes by phenotypic similarity. Specifically, we examined several candidates including the largely uncharacterized gene DONSON, which shared phenotype similarity with known factors of DNA damage response (DDR) and genomic integrity. Experimental evidence supports that DONSON is a novel centrosomal protein required for DDR signalling and genomic integrity. Multiparametric phenotyping by automated imaging and computational annotation is a powerful method for functional discovery and mapping the landscape of phenotypic responses to cellular perturbations.
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影响因子：
12.3
作者：
Kim WK;Krumpelman C;Marcotte EM
通讯作者：
Marcotte EM
DOI：
10.1083/jcb.200706150
发表时间：
2007-12-31
期刊：
The Journal of cell biology
影响因子：
--
作者：
Jørgensen S;Elvers I;Trelle MB;Menzel T;Eskildsen M;Jensen ON;Helleday T;Helin K;Sørensen CS
通讯作者：
Sørensen CS
DOI：
10.1083/jcb.200704138
发表时间：
2007-11-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Liu E;Lee AY;Chiba T;Olson E;Sun P;Wu X
通讯作者：
Wu X
DOI：
10.1083/jcb.200707181
发表时间：
2007-10-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Graser S;Stierhof YD;Lavoie SB;Gassner OS;Lamla S;Le Clech M;Nigg EA
通讯作者：
Nigg EA
影响因子：
5.3
作者：
Liu, Shizhou;Bekker-Jensen, Simon;Lukas, Jiri
通讯作者：
Lukas, Jiri