Mapping the effects of drugs on the immune system.
Mapping the effects of drugs on the immune system.
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DOI：
10.1038/nbt.3367
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发表时间：
2016-01
影响因子：
46.9
通讯作者：
Dudley JT
中科院分区：
文献类型：
--
作者：
Kidd BA;Wroblewska A;Boland MR;Agudo J;Merad M;Tatonetti NP;Brown BD;Dudley JT
了解药物如何影响免疫系统对于治疗疾病和最大限度地减少不必要的副作用具有重要意义。在这里，我们提出了一个综合的计算方法来预测药物和免疫细胞之间的相互作用，在一个系统范围内的方式。该方法匹配转录签名之间的基因集，以确定它们的相似性。我们应用该方法对1,309种药物和221种免疫细胞类型之间的相互作用进行了建模，并预测了69,995种已知和新的相互作用。由此产生的免疫细胞药理学图谱用于预测5种药物如何影响人类和小鼠的4种免疫细胞类型。为了验证预测，我们分析了患者记录并检查了体内实验中的细胞群变化。我们的方法提供了一种工具，用于筛选数千种相互作用，以确定药物和免疫系统之间的关系。
Understanding how drugs affect the immune system has consequences for treating disease and minimizing unwanted side effects. Here we present an integrative computational approach for predicting interactions between drugs and immune cells in a system-wide manner. The approach matches gene sets between transcriptional signatures to determine their similarity. We apply the method to model the interactions between 1,309 drugs and 221 immune cell types and predict 69,995 known and novel interactions. The resulting immune-cell pharmacology map is used to predict how 5 drugs influence 4 immune cell types in humans and mice. To validate the predictions, we analyzed patient records and examined cell population changes from in vivo experiments. Our method offers a tool for screening thousands of interactions to identify relationships between drugs and the immune system.