Genome-scale analysis of interactions between genetic perturbations and natural variation.

IF 6.3 2区 经济学 Q1 BUSINESS, FINANCE
Joseph J Hale, Takeshi Matsui, Ilan Goldstein, Martin N Mullis, Kevin R Roy, Chris Ne Ville, Darach Miller, Charley Wang, Trevor Reynolds, Lars M Steinmetz, Sasha F Levy, Ian M Ehrenreich
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引用次数: 0

Abstract

Interactions between genetic perturbations and segregating loci can cause perturbations to show different phenotypic effects across genetically distinct individuals. To study these interactions on a genome scale in many individuals, we used combinatorial DNA barcode sequencing to measure the fitness effects of 7,700 CRISPRi perturbations targeting 1,712 distinct genes in 169 yeast cross progeny (or segregants). We identified 460 genes whose perturbation has different effects across segregants. Several factors caused perturbations to show variable effects, including baseline segregant fitness, the mean effect of a perturbation across segregants, and interacting loci. We mapped 234 interacting loci and found four hub loci that interact with many different perturbations. Perturbations that interact with a given hub exhibit similar epistatic relationships with the hub and show enrichment for cellular processes that may mediate these interactions. These results suggest that an individual's response to perturbations is shaped by a network of perturbation-locus interactions that cannot be measured by approaches that examine perturbations or natural variation alone.

基因组尺度分析遗传扰动与自然变异之间的相互作用。
基因扰动与分离位点之间的相互作用会导致扰动在不同基因个体中表现出不同的表型效应。为了在许多个体的基因组尺度上研究这些相互作用,我们使用组合 DNA 条形码测序技术,测量了在 169 个酵母杂交后代(或分离子)中针对 1 712 个不同基因的 7 700 个 CRISPRi 扰动的适应性效应。我们确定了 460 个基因,这些基因的扰动对不同的杂交后代产生了不同的影响。有几个因素导致扰动产生不同的效应,包括基线分离适配性、扰动对不同分离子的平均效应以及相互作用位点。我们绘制了 234 个相互作用位点的图谱,并发现了与许多不同扰动相互作用的四个中心位点。与特定枢纽相互作用的扰动与枢纽表现出相似的表观关系,并显示出可能介导这些相互作用的细胞过程的富集。这些结果表明,个体对扰动的反应是由扰动-基因座相互作用网络形成的,而这种网络无法通过单独研究扰动或自然变异的方法来测量。
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来源期刊
CiteScore
11.20
自引率
9.20%
发文量
240
期刊介绍: Research in International Business and Finance (RIBAF) seeks to consolidate its position as a premier scholarly vehicle of academic finance. The Journal publishes high quality, insightful, well-written papers that explore current and new issues in international finance. Papers that foster dialogue, innovation, and intellectual risk-taking in financial studies; as well as shed light on the interaction between finance and broader societal concerns are particularly appreciated. The Journal welcomes submissions that seek to expand the boundaries of academic finance and otherwise challenge the discipline. Papers studying finance using a variety of methodologies; as well as interdisciplinary studies will be considered for publication. Papers that examine topical issues using extensive international data sets are welcome. Single-country studies can also be considered for publication provided that they develop novel methodological and theoretical approaches or fall within the Journal''s priority themes. It is especially important that single-country studies communicate to the reader why the particular chosen country is especially relevant to the issue being investigated. [...] The scope of topics that are most interesting to RIBAF readers include the following: -Financial markets and institutions -Financial practices and sustainability -The impact of national culture on finance -The impact of formal and informal institutions on finance -Privatizations, public financing, and nonprofit issues in finance -Interdisciplinary financial studies -Finance and international development -International financial crises and regulation -Financialization studies -International financial integration and architecture -Behavioral aspects in finance -Consumer finance -Methodologies and conceptualization issues related to finance
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