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DOI | 10.1038/s41467-018-05741-0 |
Systematic discovery of mutation-specific synthetic lethals by mining pan-cancer human primary tumor data | |
Sinha, Subarna1; Thomas, Daniel2,3; Chan, Steven4; Gao, Yang5; Brunen, Diede6; Torabi, Damoun2,3; Reinisch, Andreas2,3; Hernandez, David2,3; Chan, Andy7; Rankin, Erinn B.7,8; Bernards, Rene6; Majeti, Ravindra2,3; Dill, David L.1 | |
2017-05-31 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Canada; Netherlands |
英文摘要 | Two genes are synthetically lethal (SL) when defects in both are lethal to a cell but a single defect is non-lethal. SL partners of cancer mutations are of great interest as pharmacological targets; however, identifying them by cell line-based methods is challenging. Here we develop MiSL (Mining Synthetic Lethals), an algorithm that mines pan-cancer human primary tumour data to identify mutation-specific SL partners for specific cancers. We apply MiSL to 12 different cancers and predict 145,891 SL partners for 3,120 mutations, including known mutation-specific SL partners. Comparisons with functional screens show that MiSL predictions are enriched for SLs in multiple cancers. We extensively validate a SL interaction identified by MiSL between the IDH1 mutation and ACACA in leukaemia using gene targeting and patient-derived xenografts. Furthermore, we apply MiSL to pinpoint genetic biomarkers for drug sensitivity. These results demonstrate that MiSL can accelerate precision oncology by identifying mutation-specific targets and biomarkers. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000402390900001 |
WOS关键词 | DRUG-SENSITIVITY ; PHASE-II ; INHIBITOR ; CELL ; VULNERABILITY ; REVEALS ; SCREENS ; NETWORK ; TARGETS ; GENOME |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203978 |
专题 | 资源环境科学 |
作者单位 | 1.Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA; 2.Stanford Univ, Dept Med, Div Hematol, Canc Inst,Sch Med, Stanford, CA 94305 USA; 3.Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA; 4.Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada; 5.Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA; 6.Netherlands Canc Inst, Div Mol Carcinogenesis, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands; 7.Stanford Univ, Div Radiat & Canc Biol, Dept Radiat Oncol, Sch Med, Stanford, CA 94305 USA; 8.Stanford Univ, Dept Obstet & Gynecol, Sch Med, Stanford, CA 94305 USA |
推荐引用方式 GB/T 7714 | Sinha, Subarna,Thomas, Daniel,Chan, Steven,et al. Systematic discovery of mutation-specific synthetic lethals by mining pan-cancer human primary tumor data[J]. NATURE COMMUNICATIONS,2017,8. |
APA | Sinha, Subarna.,Thomas, Daniel.,Chan, Steven.,Gao, Yang.,Brunen, Diede.,...&Dill, David L..(2017).Systematic discovery of mutation-specific synthetic lethals by mining pan-cancer human primary tumor data.NATURE COMMUNICATIONS,8. |
MLA | Sinha, Subarna,et al."Systematic discovery of mutation-specific synthetic lethals by mining pan-cancer human primary tumor data".NATURE COMMUNICATIONS 8(2017). |
条目包含的文件 | 条目无相关文件。 |
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