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删除组工具:利用酵母缺失菌株转录组汇编来鉴定共功能基因。

DeleteomeTools: utilizing a compendium of yeast deletion strain transcriptomes to identify co-functional genes.

作者信息

Neal Maxwell L, Choudhry Sanjeev K, Aitchison John D

机构信息

Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, 98109, United States.

Department of Pediatrics, University of Washington, Seattle, WA, 98195, United States.

出版信息

NAR Genom Bioinform. 2025 Feb 27;7(1):lqaf008. doi: 10.1093/nargab/lqaf008. eCollection 2025 Mar.

DOI:10.1093/nargab/lqaf008
PMID:40041208
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11878635/
Abstract

We introduce DeleteomeTools, an R package that leverages the Deleteome compendium of yeast single-gene deletion transcriptomes to predict gene function. Primarily, the package provides functions for identifying similarities between the transcriptomic signatures of deletion strains, thereby associating genes of interest with others that may be functionally related. We describe how our software predicted a novel relationship between the yeast nucleoporin Nup170 and the Ctf18-RFC complex, which was confirmed experimentally, revealing a previously unknown link between nuclear pore complexes and the DNA replication machinery. To assess the package's broader predictive capabilities, we performed a systematic evaluation that tested how well it predicted Gene Ontology (GO) annotations already applied to the subset of genes deleted in Deleteome strains. We show that our package predicted a majority of reported GO: annotations with semantic similarities ranging from moderate to identical. We also discuss how our strategy for quantifying similarity between deletion strains, which relies on differential expression signatures, differs from other approaches that use global expression profiles, and why it has the potential to identify functional relationships that might otherwise go undetected.

摘要

我们介绍了DeleteomeTools,这是一个R软件包,它利用酵母单基因缺失转录组的Deleteome纲要来预测基因功能。该软件包主要提供用于识别缺失菌株转录组特征之间相似性的功能,从而将感兴趣的基因与其他可能功能相关的基因联系起来。我们描述了我们的软件如何预测酵母核孔蛋白Nup170与Ctf18-RFC复合物之间的新关系,这一关系已通过实验得到证实,揭示了核孔复合物与DNA复制机制之间以前未知的联系。为了评估该软件包更广泛的预测能力,我们进行了一项系统评估,测试它对已经应用于Deleteome菌株中缺失基因子集的基因本体(GO)注释的预测效果如何。我们表明,我们的软件包预测了大多数已报道的GO注释,其语义相似性从中度到完全相同。我们还讨论了我们基于差异表达特征来量化缺失菌株之间相似性的策略与其他使用全局表达谱的方法有何不同,以及为什么它有潜力识别那些可能否则会未被发现的功能关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ceda/11878635/b9133ed8afaf/lqaf008fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ceda/11878635/ff2dfc6c7e6f/lqaf008fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ceda/11878635/c2510a73cb90/lqaf008fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ceda/11878635/b9133ed8afaf/lqaf008fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ceda/11878635/ff2dfc6c7e6f/lqaf008fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ceda/11878635/c2510a73cb90/lqaf008fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ceda/11878635/b9133ed8afaf/lqaf008fig3.jpg

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本文引用的文献

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Nuclear pore complexes mediate subtelomeric gene silencing by regulating PCNA levels on chromatin.核孔复合物通过调节染色质上 PCNA 的水平来介导端粒基因沉默。
J Cell Biol. 2023 Sep 4;222(9). doi: 10.1083/jcb.202207060. Epub 2023 Jun 26.
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The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens.CAFA 挑战赛报告称,通过实验筛选,提高了数百个基因的蛋白质功能预测和新的功能注释。
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Large-scale genetic perturbations reveal regulatory networks and an abundance of gene-specific repressors.大规模的遗传扰动揭示了调控网络和大量基因特异性抑制剂。
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A role for the nucleoporin Nup170p in chromatin structure and gene silencing.核孔蛋白 Nup170p 在染色质结构和基因沉默中的作用。
Cell. 2013 Feb 28;152(5):969-83. doi: 10.1016/j.cell.2013.01.049.
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GOSemSim: an R package for measuring semantic similarity among GO terms and gene products.GO 语义相似度分析:用于测量 GO 术语和基因产物之间语义相似性的 R 包。
Bioinformatics. 2010 Apr 1;26(7):976-8. doi: 10.1093/bioinformatics/btq064. Epub 2010 Feb 23.
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