Department of Biochemistry and Molecular Biology, Centre for High-throughput Biology, University of British Columbia, 2125 East Mall, Vancouver, BC V6T 1Z4, Canada.
BMC Med Genomics. 2013 Nov 14;6:52. doi: 10.1186/1755-8794-6-52.
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.
神经退行性疾病（NDs）的特征是人类大脑中神经元的进行性丧失。尽管大多数 NDs 是散发性的，但有证据表明它们具有很强的遗传成分。因此，近年来人们做出了巨大努力，不仅要识别致病基因，还要识别修饰 NDs 严重程度的基因，即所谓的遗传修饰因子。迄今为止，还没有一个综合资源列出和交叉链接不同 NDs 的遗传修饰因子。
为了满足这一需求，我们提出了 NeuroGeM，这是第一个提供有关模型生物 D. melanogaster、C. elegans 和 S. cerevisiae 中 9 种不同 NDs 的遗传修饰因子的综合知识库。NeuroGeM 交叉链接了来自不同 NDs 的经过策展的遗传修饰因子信息，并提供了用于鉴定修饰因子的实验条件的详细信息、功能注释、同源蛋白的链接以及彩色编码的蛋白质-蛋白质相互作用网络，以可视化修饰因子相互作用。我们展示了如何通过元分析来利用该数据库生成新的认识。例如，我们揭示了果蝇基因 DnaJ-1、thread、Atx2 和 mub 是通用修饰因子，可影响多种甚至所有 NDs。
作为第一个遗传修饰因子综合资源，NeuroGeM 将帮助实验和计算科学家寻找 NDs 背后的病理生理机制。http://chibi.ubc.ca/neurogem.
