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DOI | 10.1038/s41467-019-09776-9 |
A systems-level framework for drug discovery identifies Csf1R as an anti-epileptic drug target | |
Srivastava, Prashant K.1; van Eyll, Jonathan2; Godard, Patrice3; Mazzuferi, Manuela; Delahaye-Duriez, Andree1,2,4,5; Van Steenwinckel, Juliette5; Gressens, Pierre5,6; Danis, Benedicte2; Vandenplas, Catherine2; Foerch, Patrik2; Leclercq, Karine2; Mairet-Coello, Georges2; Cardenas, Alvaro2; Vanclef, Frederic2; Laaniste, Liisi1; Niespodziany, Isabelle2; Keaney, James2; Gasser, Julien2; Gillet, Gaelle2; Shkura, Kirill1; Chong, Seon-Ah2; Behmoaras, Jacques7; Kadiu, Irena2; Petretto, Enrico8,9; Kaminski, Rafal M.2; Johnson, Michael R.1 | |
2019-04-23 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | England; Belgium; USA; France; Singapore |
英文摘要 | The identification of drug targets is highly challenging, particularly for diseases of the brain. To address this problem, we developed and experimentally validated a general computational framework for drug target discovery that combines gene regulatory information with causal reasoning ("Causal Reasoning Analytical Framework for Target discovery"-CRAFT). Using a systems genetics approach and starting from gene expression data from the target tissue, CRAFT provides a predictive framework for identifying cell membrane receptors with a direction-specified influence over disease-related gene expression profiles. As proof of concept, we applied CRAFT to epilepsy and predicted the tyrosine kinase receptor Csf1R as a potential therapeutic target. The predicted effect of Csf1R blockade in attenuating epilepsy seizures was validated in three pre-clinical models of epilepsy. These results highlight CRAFT as a systems-level framework for target discovery and suggest Csf1R blockade as a novel therapeutic strategy in epilepsy. CRAFT is applicable to disease settings other than epilepsy. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000443466700001 |
WOS关键词 | TEMPORAL-LOBE EPILEPSY ; GENE-EXPRESSION ; PILOCARPINE MODEL ; NETWORK ; SEIZURES ; DRIVERS ; OPINION ; DISEASE ; CELL ; EEG |
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/204337 |
专题 | 资源环境科学 |
作者单位 | 1.Imperial Coll London, Div Brain Sci, London W12 0NN, England; 2.UCB Pharma, Ave Ind,Braine IAlleud R9, B-1420 Braine Lalleud, Belgium; 3.Clarivate Analyt, 5901 Priestly Dr,200, Carlsbad, CA 92008 USA; 4.Univ Paris 13, UFR Sante Med & Biol Humaine, Sorbonne Paris Cite, Bobigny, France; 5.Univ Paris Diderot, PROTECT, INSERM, Sorbonne Paris Cite, Paris, France; 6.Kings Coll London, Sch Biomed Engn & Imaging Sci, St Thomas Hosp, Ctr Developing Brain, London SE1 7EH, England; 7.Imperial Coll London, Ctr Complement & Inflammat Res, London W12 0NN, England; 8.Duke NUS Med Sch, Ctr Computat Biol, 8 Coll Rd, Singapore 169857, Singapore; 9.Imperial Coll London, MRC Clin Sci Ctr, Fac Med, London W12 0NN, England |
推荐引用方式 GB/T 7714 | Srivastava, Prashant K.,van Eyll, Jonathan,Godard, Patrice,et al. A systems-level framework for drug discovery identifies Csf1R as an anti-epileptic drug target[J]. NATURE COMMUNICATIONS,2019,9. |
APA | Srivastava, Prashant K..,van Eyll, Jonathan.,Godard, Patrice.,Mazzuferi, Manuela.,Delahaye-Duriez, Andree.,...&Johnson, Michael R..(2019).A systems-level framework for drug discovery identifies Csf1R as an anti-epileptic drug target.NATURE COMMUNICATIONS,9. |
MLA | Srivastava, Prashant K.,et al."A systems-level framework for drug discovery identifies Csf1R as an anti-epileptic drug target".NATURE COMMUNICATIONS 9(2019). |
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