A Library of Phosphoproteomic and Chromatin Signatures for Characterizing Cellular Responses to Drug Perturbations.
A Library of Phosphoproteomic and Chromatin Signatures for Characterizing Cellular Responses to Drug Perturbations.
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DOI：
10.1016/j.cels.2018.03.012
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发表时间：
2018-04-25
期刊：
影响因子：
9.3
通讯作者：
Jaffe JD
中科院分区：
文献类型：
--
作者：
Litichevskiy L;Peckner R;Abelin JG;Asiedu JK;Creech AL;Davis JF;Davison D;Dunning CM;Egertson JD;Egri S;Gould J;Ko T;Johnson SA;Lahr DL;Lam D;Liu Z;Lyons NJ;Lu X;MacLean BX;Mungenast AE;Officer A;Natoli TE;Papanastasiou M;Patel J;Sharma V;Toder C;Tubelli AA;Young JZ;Carr SA;Golub TR;Subramanian A;MacCoss MJ;Tsai LH;Jaffe JD
虽然蛋白质组学的价值已被证明，成本和规模通常是令人望而却步的，基因表达谱仍然占主导地位的表征细胞对扰动的反应。然而，高通量前哨检测为蛋白质组学提供了一个机会，以有意义的规模作出贡献。我们提出了一个系统的图书馆资源（90种药物3 - 6细胞系）的蛋白质组学签名，测量减少代表磷酸化蛋白质组（P100）的变化和组蛋白（GCP）表观遗传标记的变化。这些药物中的大多数引起了可重复的签名，但观察到显著的细胞系和测定特异性差异。使用“连接性”框架，我们比较了不同细胞类型的特征，并整合了包括转录测定（L1000）在内的测定数据。细胞类型之间的一致连接性揭示了超越谱系的细胞反应，并且测定之间的一致连接性揭示了药物之间的意外关联。我们进一步利用公共数据的资源来制定治疗多发性骨髓瘤和急性淋巴细胞白血病的假设。此资源可在https://clue.io/proteomics上公开获取。通过磷酸化信号传导和组蛋白修饰的蛋白质组学分析，对药物的细胞反应的一个大型纲要揭示了超越谱系的细胞反应，发现了药物之间的意外关联，并认识到治疗多发性骨髓瘤和急性淋巴细胞白血病的治疗假设。
Although the value of proteomics has been demonstrated, cost and scale are typically prohibitive, and gene expression profiling remains dominant for characterizing cellular responses to perturbations. However, high-throughput sentinel assays provide an opportunity for proteomics to contribute at a meaningful scale. We present a systematic library resource (90 drugs 3 6 cell lines) of proteomic signatures that measure changes in the reduced-representation phosphoproteome (P100) and changes in epigenetic marks on histones (GCP). A majority of these drugs elicited reproducible signatures, but notable cell line- and assay-specific differences were observed. Using the “connectivity” framework, we compared signatures across cell types and integrated data across assays, including a transcriptional assay (L1000). Consistent connectivity among cell types revealed cellular responses that transcended lineage, and consistent connectivity among assays revealed unexpected associations between drugs. We further leveraged the resource against public data to formulate hypotheses for treatment of multiple myeloma and acute lymphocytic leukemia. This resource is publicly available at https://clue.io/proteomics. A large compendium of cellular responses to drugs as profiled through proteomic assays of phosphosignaling and histone modifications reveals cellular responses that transcend lineage, discovers unexpected associations between drugs, and recognizes therapeutic hypotheses for treatment of multiple myeloma and acute lymphocytic leukemia.
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影响因子：
--
作者：
Iacovelli S;Ricciardi MR;Allegretti M;Mirabilii S;Licchetta R;Bergamo P;Rinaldo C;Zeuner A;Foà R;Milella M;McCubrey JA;Martelli AM;Tafuri A
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作者：
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作者：
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通讯作者：
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影响因子：
3.3
作者：
Bian, Yangyang;Song, Chunxia;Zou, Hanfa
通讯作者：
Zou, Hanfa