Discovering New Genes in the Pathways of Common Sporadic Neurodegenerative Diseases: A Bioinformatics Approach
Discovering New Genes in the Pathways of Common Sporadic Neurodegenerative Diseases: A Bioinformatics Approach
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DOI：
10.3233/jad-150769
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发表时间：
2016-01-01
影响因子：
4
通讯作者：
Song, Min
中科院分区：
文献类型：
--
作者：
Kim, Yong Hwan;Beak, Seung Han;Song, Min
晚发性阿尔茨海默病(AD)和帕金森氏病(PD)大多是与年龄相关的散发性神经退行性疾病，但有明确的遗传成分。然而，它们的遗传结构是复杂和异质的，在很大程度上仍然是一个难题，只有少数公认的遗传风险因素与这些疾病持续相关。有可能存在许多尚未发现的AD和PD相关基因。我们利用生物文献挖掘技术，将“基因”作为中介，寻找可能与这两种疾病有关的新的潜在基因。基于Entrez基因，我们提取了整个MEDLINE记录中的基因和方向性基因-基因关系，构建了方向性基因-基因网络。我们通过对网络进行最短路径分析，确定了与两种不同但相关的疾病相关的共同基因。通过我们的方法，我们能够识别和定位与PD和AD有直接关系的已知基因。此外，我们还鉴定了7个以前未知的基因，它们是这两种疾病之间的桥梁。我们通过生物医学文献证实了4个基因ROS1、FMN1、ATP8A2和SNORD12C，并进一步验证了3个基因ERVK-10、PrS和C7orf49可能与这两种疾病有很高的相关性。另外还进行了实验，以验证所提方法的有效性。与共现法相比，我们的方法检测到的候选基因多了25%，验证了与两种疾病之间有关系的基因多了10%。
Late onset Alzheimer's disease (AD) and Parkinson's disease (PD) are mostly "sporadic" age-related neurode-generative disorders, but with a clear genetic component. However, their genetic architecture is complex and heterogeneous, largely remaining a conundrum, with only a handful of well-established genetic risk factors consistently associated with these diseases. It is possible that numerous, yet undiscovered, AD and PD related genes might exist. We focused on the 'gene' as a mediator to find new potential genes that might have a relationship with both disorders using bio-literature mining techniques. Based on Entrez Gene, we extracted the genes and directional gene-gene relation in the entire MEDLINE records and then constructed a directional gene-gene network. We identified common genes associated with two different but related diseases by performing shortest path analysis on the network. With our approach, we were able to identify and map already known genes that have a direct relationship with PD and AD. In addition, we identified 7 genes previously unknown to be a bridge between these two disorders. We confirmed 4 genes, ROS1, FMN1, ATP8A2, and SNORD12C, by biomedical literature and further checked 3 genes, ERVK-10, PRS, and C7orf49, that might have a high possibility to be related with both diseases. Additional experiments were performed to demonstrate the effectiveness of our proposed method. Comparing to the co-occurrence approach, our approach detected 25% more candidate genes and verified 10% more genes that have the relationship between both diseases than the co-occurrence approach did.