小柯机器人

美国斯坦福大学Anshul Kundaje、Michael C. Bassik等研究人员合作利用全基因组共同模块图谱为未知基因赋予功能。相关论文于2021年4月15日在线发表在《自然—遗传学》杂志上。

研究人员开发了一种统计方法，能够可靠地鉴定基因的共同必需性，并产生全基因组范围的功能模块。该图谱概括了各种途径和蛋白质复合物，并预测了108个未表征基因的功能。通过验证最高的预测，研究人员发现TMEM189编码plasmaylethanolamine去饱和酶，这是缩醛磷脂合成的关键酶。研究人员还显示，C15orf57编码结合AP2复合物的蛋白质，定位于网格蛋白包被的凹坑，并能有效地吸收转铁蛋白。最后，研究人员提供了一个交互式的网络工具来探索这些结果，从而将共同本质分析建立为生物学途径识别和发现新基因功能的有力资源。

据介绍，后基因组时代的一个核心问题是基因如何相互作用形成生物学途径。跨数百种细胞系的基因依赖性测量已用于将基因聚类为“共同必需”途径，但这种方法受到普遍存在的假阳性的局限。

附：英文原文

Title: A genome-wide atlas of co-essential modules assigns function to uncharacterized genes

Author: Michael Wainberg, Roarke A. Kamber, Akshay Balsubramani, Robin M. Meyers, Nasa Sinnott-Armstrong, Daniel Hornburg, Lihua Jiang, Joanne Chan, Ruiqi Jian, Mingxin Gu, Anna Shcherbina, Michael M. Dubreuil, Kaitlyn Spees, Wouter Meuleman, Michael P. Snyder, Michael C. Bassik, Anshul Kundaje

Issue&Volume: 2021-04-15

Abstract: A central question in the post-genomic era is how genes interact to form biological pathways. Measurements of gene dependency across hundreds of cell lines have been used to cluster genes into ‘co-essential’ pathways, but this approach has been limited by ubiquitous false positives. In the present study, we develop a statistical method that enables robust identification of gene co-essentiality and yields a genome-wide set of functional modules. This atlas recapitulates diverse pathways and protein complexes, and predicts the functions of 108 uncharacterized genes. Validating top predictions, we show that TMEM189 encodes plasmanylethanolamine desaturase, a key enzyme for plasmalogen synthesis. We also show that C15orf57 encodes a protein that binds the AP2 complex, localizes to clathrin-coated pits and enables efficient transferrin uptake. Finally, we provide an interactive webtool for the community to explore our results, which establish co-essentiality profiling as a powerful resource for biological pathway identification and discovery of new gene functions.

DOI: 10.1038/s41588-021-00840-z

Source: https://www.nature.com/articles/s41588-021-00840-z

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex