Volume 26, No 9, Sep 2016

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 26 Issue 9, September 2016: 1067-1070

LETTERS TO THE EDITOR

A genome-wide loss-of-function screening method for minimizing false-negatives caused by functional redundancy

Li Mao^1,*, Chenglin Liu^2,3,*, Zhen Wang², Xiaofeng Niu¹, Liang Xue¹, Zhilei Zhou¹, Zhenying Cai¹, Meng Yu^1,4, Yixue Li^2,3,5, Dianqing Wu⁶ and Lin Li¹

¹State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai 200031, China
²Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
³School of Life Sciences and Biotechnology, Shanghai Jiaotong University, Shanghai, China
⁴School of Life Science and Technology, Shanghai Tech University, Shanghai 200031, China
⁵Collaborative Innovation Center for Genetics and Development, Fudan University, Shanghai, China
⁶Vascular Biology and Therapeutic Program and Department of Pharmacology, Yale School of Medicine, New Haven, CT 06520, USA Correspondence: Lin Li, E-mail: lli@sibs.ac.cn; Dianqing Wu, E-mail: dianqing.wu@yale.edu; Yixue Li,(yxli@sibs.ac.cn)

Loss-of-function screens are powerful tools for identifying gene contribution in a given biological context. Over the past decade, the RNA interference technology has become a dominant approach in the loss-of-function screen-based gene discovery1. However, about 3 quarters of genes in mammalian genomes belong to gene families and have functional redundant homologs. While this functional redundancy protects cells and organisms from deleterious mutations2, it also masks phenotypic outcomes, resulting in false-negatives in loss-of-function screens that target individual genes. However, all of reported loss-of-function screens have been designed to target individual genes and thus suffer from limitations of the false-negatives.

10.1038/cr.2016.97

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