A functional variomics tool for discovering drug-resistance genes and drug targets.
A functional variomics tool for discovering drug-resistance genes and drug targets.
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DOI：
10.1016/j.celrep.2013.01.019
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发表时间：
2013-02-21
期刊：
影响因子：
8.8
通讯作者：
Pan X
中科院分区：
文献类型：
--
作者：
Huang Z;Chen K;Zhang J;Li Y;Wang H;Cui D;Tang J;Liu Y;Shi X;Li W;Liu D;Chen R;Sucgang RS;Pan X
全面发现耐药的遗传机制和确定体内药物靶点是一项重大挑战。在这里，我们提出了一种模式生物酿酒酵母的功能变异组学技术。这一工具分析了大量的遗传变异，并有效地同时解决了这两个问题。利用这一工具，我们发现了几乎所有由于突变或适度过度表达而导致对雷帕霉素、环己亚胺和两性霉素B产生耐药性的基因。最显著的耐药性基因是药物靶点，包括给定药物的多个靶点。对于两性霉素B，我们发现高度保守的膜蛋白Pmp3是一种强大的抗性因子，可能是一个新的靶点。这一工具的广泛应用应该能够快速识别保守的抗性机制和更多化合物的靶标。新的基因和等位基因也可以被发现，这些基因和等位基因赋予了对其他压力的抗性。人类细胞系等其他系统中的类似工具也将是有用的。
Comprehensive discovery of genetic mechanisms of drug resistance and identification of in vivo drug targets represent significant challenges. Here we present a functional variomics technology in the model organism Saccharomyces cerevisiae. This tool analyzes numerous genetic variants and effectively tackles both problems simultaneously. Using this tool, we discovered almost all genes that, due to mutations or modest overexpression, confer resistance to rapamycin, cycloheximide, and amphotericin B. Most significant among the resistance genes were drug targets, including multiple targets of a given drug. With amphotericin B, we discovered the highly conserved membrane protein Pmp3 as a potent resistance factor and a possible novel target. Widespread application of this tool should allow rapid identification of conserved resistance mechanisms and targets of many more compounds. New genes and alleles that confer resistance to other stresses can also be discovered. Similar tools in other systems such as human cell lines will also be useful.
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影响因子：
46.9
作者：
通讯作者：
--
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
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通讯作者：
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影响因子：
2.1
作者：
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通讯作者：
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影响因子：
5.3
作者：
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通讯作者：
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DOI：
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发表时间：
2010-01-22
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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通讯作者：
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