Essential genes from genome-wide screenings as a resource for neuropsychiatric disorders gene discovery.
Essential genes from genome-wide screenings as a resource for neuropsychiatric disorders gene discovery.
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来自全基因组筛查的基本基因作为神经精神疾病的资源基因发现。
DOI：
10.1038/s41398-021-01447-y
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发表时间：
2021-05-25
影响因子：
6.8
通讯作者：
Fries GR
中科院分区：
文献类型：
--
作者：
Zhang W;Quevedo J;Fries GR
全基因组筛选“必需基因”，即，生物体或细胞存活所需的基因，传统上在癌细胞系中进行体外检测，限制了结果对其他组织和非癌细胞的转化。最近，在成年小鼠纹状体组织中进行了体内筛选，提供了神经元细胞中必需基因的第一个全基因组数据集。在这里，我们的目标是调查大脑发育和疾病风险的重要基因的作用与一套全面的生物信息学工具，包括整合从开发人类大脑的转录组数据，从全基因组关联研究，从头突变数据集不同的神经精神疾病，和病例对照转录组数据从死后脑组织。本研究首次发现神经元必需基因（neuronal essential genes，NEGs）在人脑发育早期的表达在出生前增加，并在出生后保持较高的表达水平。相反，来自癌细胞系筛选（ACEGs）的常见必需基因往往在发育期间以高水平表达，但在出生后迅速下降。这两个基因集都富含神经发育障碍，但只有NEGs与神经精神障碍风险基因密切相关。最后，NEGs比ACEGs更可能在神经精神疾病患者的大脑中显示差异表达。总的来说，全基因组中枢神经系统必需基因的筛查可以为神经精神疾病提供新的见解。
Genome-wide screenings of “essential genes”, i.e., genes required for an organism or cell survival, have been traditionally conducted in vitro in cancer cell lines, limiting the translation of results to other tissues and non-cancerous cells. Recently, an in vivo screening was conducted in adult mouse striatum tissue, providing the first genome-wide dataset of essential genes in neuronal cells. Here, we aim to investigate the role of essential genes in brain development and disease risk with a comprehensive set of bioinformatics tools, including integration with transcriptomic data from developing human brain, publicly available data from genome-wide association studies, de novo mutation datasets for different neuropsychiatric disorders, and case–control transcriptomic data from postmortem brain tissues. For the first time, we found that the expression of neuronal essential genes (NEGs) increases before birth during the early development of human brain and maintains a relatively high expression after birth. On the contrary, common essential genes from cancer cell line screenings (ACEGs) tend to be expressed at high levels during development but quickly drop after birth. Both gene sets were enriched in neurodevelopmental disorders, but only NEGs were robustly associated with neuropsychiatric disorders risk genes. Finally, NEGs were more likely to show differential expression in the brains of neuropsychiatric disorders patients than ACEGs. Overall, genome-wide central nervous system screening of essential genes can provide new insights into neuropsychiatric diseases.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
4.4
作者：
Fried EI;van Borkulo CD;Cramer AO;Boschloo L;Schoevers RA;Borsboom D
通讯作者：
Borsboom D
影响因子：
56.9
作者：
Li, Mingfeng;Santpere, Gabriel;Sanders, Stephan
通讯作者：
Sanders, Stephan
DOI：
10.1080/15384101.2015.1004937
发表时间：
2015
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Frade JM;Ovejero-Benito MC
通讯作者：
Ovejero-Benito MC