Accurate Drug Repositioning through Non-tissue-Specific Core Signatures from Cancer Transcriptomes
文献类型：期刊论文
| 作者 | Xu, Chi1,2; Ai, Daosheng2; Suo, Shengbao2; Chen, Xingwei1,2; Yan, Yizhen1,2; Cao, Yaqiang1,2; Sun, Na2; Chen, Weizhong2; McDermott, Joseph2; Zhang, Shiqiang1,2 |
| 刊名 | CELL REPORTS
 |
| 出版日期 | 2018 |
| 卷号 | 25期号:2页码:523-+ |
| 关键词 | Skin color Natural selection Genetic adaptation Modern humans Archaic hominin |
| ISSN号 | 2211-1247 |
| DOI | 10.1016/j.celrep.2018.09.031 |
| 文献子类 | Article |
| 英文摘要 | Experimental large-scale screens for drug repositioning are limited by restriction to in vitro conditions and lack of applicability to real human conditions. Here, we developed an in silico screen in human in vivo conditions using a reference of single gene mutations' non-tissue-specific "core transcriptome signatures" (CSs) of 8,476 genes generated from the TCGA database. We developed the core-signature drug-to-gene (csD2G) software to scan 3,546 drug treatment profiles against the reference signatures. csD2G significantly outperformed conventional cell line-based gene perturbation signatures and existing drug-repositioning methods in both coverage and specificity. We highlight this with 3 demonstrated applications: (1) repositioned category of psychiatric drugs to inhibit the TGF-beta pathway; (2) antihypertensive calcium channel blockers predicted to activate AMPK and inhibit AKT pathways, and validated by clinical electronic medical records; and (3) 7 drugs predicted and validated to selectively target the AKT-FOXO and AMPK pathways and thus regulate worm lifespan. |
| 学科主题 | Cell Biology |
| WOS关键词 | CONNECTIVITY MAP ; GENE-EXPRESSION ; TGF-BETA ; CELLS ; NETWORK ; GENOME ; KINASE ; AKT ; DIFFERENTIATION ; LONGEVITY |
| 语种 | 英语 |
| WOS记录号 | WOS:000446691400024 |
| 出版者 | CELL PRESS |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/985]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China, 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Ctr Excellence Mol Cell Sci,Key Lab Computat Biol, Collaborat Innovat Ctr Genet & Dev Biol,Max Planc, Shanghai 200031, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Xu, Chi,Ai, Daosheng,Suo, Shengbao,et al. Accurate Drug Repositioning through Non-tissue-Specific Core Signatures from Cancer Transcriptomes[J]. CELL REPORTS,2018,25(2):523-+. |
| APA | Xu, Chi.,Ai, Daosheng.,Suo, Shengbao.,Chen, Xingwei.,Yan, Yizhen.,...&,.(2018).Accurate Drug Repositioning through Non-tissue-Specific Core Signatures from Cancer Transcriptomes.CELL REPORTS,25(2),523-+. |
| MLA | Xu, Chi,et al."Accurate Drug Repositioning through Non-tissue-Specific Core Signatures from Cancer Transcriptomes".CELL REPORTS 25.2(2018):523-+. |
入库方式： OAI收割
来源：上海营养与健康研究所
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