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DOI | 10.1126/science.aax4438 |
Exploring genetic interaction manifolds constructed from rich single-cell phenotypes | |
Norman, Thomas M.1,2,3; Horlbeck, Max A.1,2,3; Replogle, Joseph M.1,2,3; Ge, Alex Y.4,5; Xu, Albert1,2,3; Jost, Marco1,2,3; Gilbert, Luke A.4,5; Weissman, Jonathan S.1,2,3 | |
2019-08-23 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 365期号:6455页码:786-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | How cellular and organismal complexity emerges from combinatorial expression of genes is a central question in biology. High-content phenotyping approaches such as Perturb-seq (single-cell RNA-sequencing pooled CRISPR screens) present an opportunity for exploring such genetic interactions (GIs) at scale. Here, we present an analytical framework for interpreting high-dimensional landscapes of cell states (manifolds) constructed from transcriptional phenotypes. We applied this approach to Perturb-seq profiling of strong GIs mined from a growth-based. gain-of-function GI map. Exploration of this manifold enabled ordering of regulatory pathways, principled classification of GIs (e.g., identifying suppressors). and mechanistic elucidation of synergistic interactions, including an unexpected synergy between CBL and CNN1 driving erythroid differentiation. Finally, we applied recommender system machine learning to predict interactions. facilitating exploration of vastly larger GI manifolds. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000482464000047 |
WOS关键词 | EXPRESSION ; CIRCUITS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
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/202132 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA; 2.Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA; 3.Univ Calif San Francisco, Calif Inst Quantitat Biomed Res, San Francisco, CA 94158 USA; 4.Univ Calif San Francisco, Dept Urol, San Francisco, CA 94158 USA; 5.Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA |
推荐引用方式 GB/T 7714 | Norman, Thomas M.,Horlbeck, Max A.,Replogle, Joseph M.,et al. Exploring genetic interaction manifolds constructed from rich single-cell phenotypes[J]. SCIENCE,2019,365(6455):786-+. |
APA | Norman, Thomas M..,Horlbeck, Max A..,Replogle, Joseph M..,Ge, Alex Y..,Xu, Albert.,...&Weissman, Jonathan S..(2019).Exploring genetic interaction manifolds constructed from rich single-cell phenotypes.SCIENCE,365(6455),786-+. |
MLA | Norman, Thomas M.,et al."Exploring genetic interaction manifolds constructed from rich single-cell phenotypes".SCIENCE 365.6455(2019):786-+. |
条目包含的文件 | 条目无相关文件。 |
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