Correction of a widespread bias in pooled chemical genomics screens improves their interpretability.

IF 8.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Systems Biology Pub Date : 2024-11-01 Epub Date: 2024-09-30 DOI:10.1038/s44320-024-00069-y
Lili M Kim, Horia Todor, Carol A Gross
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Abstract

Chemical genomics is a powerful and increasingly accessible technique to probe gene function, gene-gene interactions, and antibiotic synergies and antagonisms. Indeed, multiple large-scale pooled datasets in diverse organisms have been published. Here, we identify an artifact arising from uncorrected differences in the number of cell doublings between experiments within such datasets. We demonstrate that this artifact is widespread, show how it causes spurious gene-gene and drug-drug correlations, and present a simple but effective post hoc method for removing its effects. Using several published datasets, we demonstrate that this correction removes spurious correlations between genes and conditions, improving data interpretability and revealing new biological insights. Finally, we determine experimental factors that predispose a dataset for this artifact and suggest a set of experimental and computational guidelines for performing pooled chemical genomics experiments that will maximize the potential of this powerful technique.

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纠正集合化学基因组学筛选中的普遍偏差,提高其可解释性。
化学基因组学是一项功能强大且越来越容易获得的技术,可用于探究基因功能、基因与基因之间的相互作用以及抗生素的协同作用和拮抗作用。事实上,多种生物的大规模集合数据集已经发表。在这里,我们发现了由于此类数据集中不同实验之间细胞倍增数的差异未得到校正而产生的假象。我们证明了这种假象的普遍性,展示了它如何导致虚假的基因-基因和药物-药物相关性,并提出了一种简单而有效的事后方法来消除其影响。通过使用几个已发表的数据集,我们证明了这种校正可以消除基因和条件之间的虚假相关性,从而提高数据的可解释性并揭示新的生物学观点。最后,我们确定了导致数据集出现这种伪影的实验因素,并提出了一套进行集合化学基因组学实验的实验和计算指南,以最大限度地发挥这项强大技术的潜力。
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来源期刊
Molecular Systems Biology
Molecular Systems Biology 生物-生化与分子生物学
CiteScore
18.50
自引率
1.00%
发文量
62
审稿时长
6-12 weeks
期刊介绍: Systems biology is a field that aims to understand complex biological systems by studying their components and how they interact. It is an integrative discipline that seeks to explain the properties and behavior of these systems. Molecular Systems Biology is a scholarly journal that publishes top-notch research in the areas of systems biology, synthetic biology, and systems medicine. It is an open access journal, meaning that its content is freely available to readers, and it is peer-reviewed to ensure the quality of the published work.
期刊最新文献
Identifying T-cell clubs by embracing the local harmony between TCR and gene expressions. XCMS-METLIN: data-driven metabolite, lipid, and chemical analysis. Author Correction: Predictive evolution of metabolic phenotypes using model-designed environments. Correction of a widespread bias in pooled chemical genomics screens improves their interpretability. Prediction of the 3D cancer genome from whole-genome sequencing using InfoHiC.
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