NeuroGeM, a knowledgebase of genetic modifiers in neurodegenerative diseases.

NeuroGeM, a knowledgebase of genetic modifiers in neurodegenerative diseases.
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DOI:
10.1186/1755-8794-6-52
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发表时间:
2013-11-14
影响因子:
2.7
通讯作者:
Gsponer J
Gsponer J
中科院分区:
医学3区
文献类型:
--
作者:
Na D;Rouf M;O'Kane CJ;Rubinsztein DC;Gsponer J

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神经退行性疾病(ND)的特征在于人脑中神经元的进行性损失。虽然大多数ND是散发性的,但越来越多的证据表明它们具有很强的遗传成分。因此,近年来已经做出了重大努力,不仅要识别致病基因,还要识别改变ND严重程度的基因,即所谓的遗传修饰剂。到目前为止,还没有列出和交叉链接不同ND的遗传修饰剂的汇编。为了解决这一需求,我们提出了NeuroGeM,第一个全面的知识库,提供综合信息的遗传修饰剂的9个不同的ND在模式生物D。melanogaster、黑腹隐翅虫C. elegans和S.啤酒。NeuroGeM交叉链接来自不同ND的策划遗传修饰剂信息,并提供用于修饰剂鉴定,功能注释,同源蛋白质和颜色编码蛋白质-蛋白质相互作用网络的链接的实验条件的详细信息,以可视化修饰剂相互作用。我们展示了如何使用这个数据库,通过荟萃分析产生新的理解。例如,我们发现,果蝇基因DnaJ-1,线程,Atx 2,和MUB是通用的修改器,影响多个,如果不是所有的ND。作为遗传修饰剂的第一个纲要,NeuroGeM将帮助实验和计算科学家寻找ND的病理生理机制。http://chibi.ubc.ca/neurogem.
Neurodegenerative diseases (NDs) are characterized by the progressive loss of neurons in the human brain. Although the majority of NDs are sporadic, evidence is accumulating that they have a strong genetic component. Therefore, significant efforts have been made in recent years to not only identify disease-causing genes but also genes that modify the severity of NDs, so-called genetic modifiers. To date there exists no compendium that lists and cross-links genetic modifiers of different NDs. In order to address this need, we present NeuroGeM, the first comprehensive knowledgebase providing integrated information on genetic modifiers of nine different NDs in the model organisms D. melanogaster, C. elegans, and S. cerevisiae. NeuroGeM cross-links curated genetic modifier information from the different NDs and provides details on experimental conditions used for modifier identification, functional annotations, links to homologous proteins and color-coded protein-protein interaction networks to visualize modifier interactions. We demonstrate how this database can be used to generate new understanding through meta-analysis. For instance, we reveal that the Drosophila genes DnaJ-1, thread, Atx2, and mub are generic modifiers that affect multiple if not all NDs. As the first compendium of genetic modifiers, NeuroGeM will assist experimental and computational scientists in their search for the pathophysiological mechanisms underlying NDs. http://chibi.ubc.ca/neurogem.
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