Quantitative assessment of protein activity in orphan tissues and single cells using the metaVIPER algorithm.
Quantitative assessment of protein activity in orphan tissues and single cells using the metaVIPER algorithm.
复制标题
DOI：
10.1038/s41467-018-03843-3
复制
发表时间：
2018-04-16
影响因子：
16.6
通讯作者：
Califano A
中科院分区：
文献类型：
--
作者：
Ding H;Douglass EF Jr;Sonabend AM;Mela A;Bose S;Gonzalez C;Canoll PD;Sims PA;Alvarez MJ;Califano A
我们和其他人已经证明，生物状态的转变和维持是由主调节蛋白控制的，这可以通过使用VIPER算法询问具有转录特征的组织特异性调节模型（相互作用组）来推断。然而，一些组织可能缺乏相互作用组推断所需的分子谱（孤儿组织），或者，对于从异质样品中分离出来的单细胞，其组织背景可能不确定。为了解决这个问题，我们引入了metaVIPER，这是一种算法，旨在通过对多个非组织匹配的相互作用组的综合分析，以组织独立的方式评估蛋白质活性。这假设每个蛋白质的转录目标将被一个或多个可用的相互作用组重述。我们证实了该算法在评估体细胞突变诱导的蛋白质失调以及评估孤儿组织中的蛋白质活性方面的价值，最重要的是，在单细胞中，从而允许将嘈杂和潜在偏差的RNA-Seq特征转化为可重复的蛋白质活性特征。VIPER已被成功地用于评估基因表达数据中蛋白质的调控活性，但其对组织特异性分子谱的依赖限制了其适用性。MetaVIPER，在这里介绍，可以推断孤儿组织和单细胞中的蛋白质活性。
We and others have shown that transition and maintenance of biological states is controlled by master regulator proteins, which can be inferred by interrogating tissue-specific regulatory models (interactomes) with transcriptional signatures, using the VIPER algorithm. Yet, some tissues may lack molecular profiles necessary for interactome inference (orphan tissues), or, as for single cells isolated from heterogeneous samples, their tissue context may be undetermined. To address this problem, we introduce metaVIPER, an algorithm designed to assess protein activity in tissue-independent fashion by integrative analysis of multiple, non-tissue-matched interactomes. This assumes that transcriptional targets of each protein will be recapitulated by one or more available interactomes. We confirm the algorithm’s value in assessing protein dysregulation induced by somatic mutations, as well as in assessing protein activity in orphan tissues and, most critically, in single cells, thus allowing transformation of noisy and potentially biased RNA-Seq signatures into reproducible protein-activity signatures. VIPER has been successfully used to assess the regulatory activities of proteins from gene expression data, but its dependence on tissue-specific molecular profiles limits its applicability. MetaVIPER, introduced here, enables inference of the protein activities in orphan tissues and single cells.
登录
查看更多内容
DOI：
10.1038/nrc.2016.124
发表时间：
2017-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Califano A;Alvarez MJ
通讯作者：
Alvarez MJ
影响因子：
16.2
作者：
Canoll, PD;Musacchio, JM;Salzer, JL
通讯作者：
Salzer, JL
影响因子：
3.7
作者：
Aubry, Soline;Shin, William;Shelanski, Michael L.
通讯作者：
Shelanski, Michael L.
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
25
作者：
Brichta, Lars;Shin, William;Greengard, Paul
通讯作者：
Greengard, Paul