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Genetic interaction networks mediate individual statin drug response in Saccharomyces cerevisiae.
npj Systems Biology and Applications ( IF 3.5 ) Pub Date : 2019-10-03 , DOI: 10.1038/s41540-019-0112-5 Bede P Busby 1, 2 , Eliatan Niktab 1 , Christina A Roberts 1 , Jeffrey P Sheridan 1 , Namal V Coorey 1 , Dinindu S Senanayake 1 , Lisa M Connor 1 , Andrew B Munkacsi 1 , Paul H Atkinson 1
npj Systems Biology and Applications ( IF 3.5 ) Pub Date : 2019-10-03 , DOI: 10.1038/s41540-019-0112-5 Bede P Busby 1, 2 , Eliatan Niktab 1 , Christina A Roberts 1 , Jeffrey P Sheridan 1 , Namal V Coorey 1 , Dinindu S Senanayake 1 , Lisa M Connor 1 , Andrew B Munkacsi 1 , Paul H Atkinson 1
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Eukaryotic genetic interaction networks (GINs) are extensively described in the Saccharomyces cerevisiae S288C model using deletion libraries, yet being limited to this one genetic background, not informative to individual drug response. Here we created deletion libraries in three additional genetic backgrounds. Statin response was probed with five queries against four genetic backgrounds. The 20 resultant GINs representing drug-gene and gene-gene interactions were not conserved by functional enrichment, hierarchical clustering, and topology-based community partitioning. An unfolded protein response (UPR) community exhibited genetic background variation including different betweenness genes that were network bottlenecks, and we experimentally validated this UPR community via measurements of the UPR that were differentially activated and regulated in statin-resistant strains relative to the statin-sensitive S288C background. These network analyses by topology and function provide insight into the complexity of drug response influenced by genetic background.
中文翻译：
遗传相互作用网络介导酿酒酵母中个体他汀类药物反应。
使用缺失文库在酿酒酵母 S288C 模型中广泛描述了真核遗传相互作用网络 (GIN)，但仅限于这一遗传背景，无法提供个体药物反应的信息。在这里，我们在三个额外的遗传背景中创建了缺失文库。通过针对四种遗传背景的五个查询来探究他汀类药物的反应。代表药物-基因和基因-基因相互作用的 20 个生成的 GIN 并未通过功能富集、层次聚类和基于拓扑的群落划分而保守。未折叠蛋白反应（UPR）群落表现出遗传背景变异，包括作为网络瓶颈的不同中介基因，我们通过测量 UPR 来实验验证了这个 UPR 群落，相对于他汀类药物敏感的菌株，UPR 在他汀类药物抗性菌株中被差异性激活和调节。 S288C背景。这些通过拓扑和功能进行的网络分析可以深入了解受遗传背景影响的药物反应的复杂性。
更新日期：2019-10-03
中文翻译：
遗传相互作用网络介导酿酒酵母中个体他汀类药物反应。
使用缺失文库在酿酒酵母 S288C 模型中广泛描述了真核遗传相互作用网络 (GIN)，但仅限于这一遗传背景，无法提供个体药物反应的信息。在这里，我们在三个额外的遗传背景中创建了缺失文库。通过针对四种遗传背景的五个查询来探究他汀类药物的反应。代表药物-基因和基因-基因相互作用的 20 个生成的 GIN 并未通过功能富集、层次聚类和基于拓扑的群落划分而保守。未折叠蛋白反应（UPR）群落表现出遗传背景变异，包括作为网络瓶颈的不同中介基因，我们通过测量 UPR 来实验验证了这个 UPR 群落，相对于他汀类药物敏感的菌株，UPR 在他汀类药物抗性菌株中被差异性激活和调节。 S288C背景。这些通过拓扑和功能进行的网络分析可以深入了解受遗传背景影响的药物反应的复杂性。
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