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注意缺陷多动障碍候选基因的网络和通路富集分析

Network and pathway enrichment analysis of Attention Deficit/Hyperactivity Disorder candidate genes.

作者信息

Singh Pratichi

机构信息

Department of Biochemistry, School of Basic and Applied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India.

出版信息

Indian J Psychiatry. 2020 Jul-Aug;62(4):400-406. doi: 10.4103/psychiatry.IndianJPsychiatry_105_17. Epub 2020 Jul 27.

Abstract

BACKGROUND

Attention deficit/hyperactivity disorder (ADHD) is a well-known multigenic neurodevelopment disorder. It is a psychiatric disease which mainly affects the children and adolescence. Globally, 3%-5% of children are suffering from this mental disorder.

AIMS AND OBJECTIVES

This disease is characterized by hyperactivity, impulsiveness and inattentiveness. Suffering individuals are also observed with sleep related problems. Though, its polygenic, to study the complexity of these genes, we used a purely network approach. Firstly, we collected all the candidate genes involved in ADHD through a literature survey.

MATERIALS AND METHODS

We investigated these genes using STRING 10 and Cytoscape v 3.3.0 for protein protein interaction network. Accordingly, we attempted to identify the hub genes based on definite parameters like betweenness centrality, clustering coefficient and node degree using Network analyzer. Likewise, the key transcriptional regulators were acknowledged by means of MatInspector program. Finally, the enrichment analysis was executed using ClueGO.

RESULTS

As a result, dopamine receptor D2, brain derived neurotrophic factor, , and dopamine receptor D4 were recognized as hub genes among the reported ADHD genes. While, 17 transcription factors (TFs) were conveyed as the key TFs for these hub genes.

CONCLUSION

Functional enrichment analysis revealed regulation of dopamine and behavioral fear response pathways. These pathways have been assumed to play a central role in the ADHD within the selected candidate genes.

摘要

背景

注意力缺陷多动障碍(ADHD)是一种广为人知的多基因神经发育障碍。它是一种主要影响儿童和青少年的精神疾病。在全球范围内,3%-5%的儿童患有这种精神障碍。

目的

这种疾病的特征是多动、冲动和注意力不集中。患病个体还存在与睡眠相关的问题。尽管它是多基因的,但为了研究这些基因的复杂性,我们采用了一种纯粹的网络方法。首先,我们通过文献调查收集了所有与ADHD相关的候选基因。

材料和方法

我们使用STRING 10和Cytoscape v 3.3.0研究这些基因的蛋白质-蛋白质相互作用网络。相应地,我们试图使用网络分析器根据介数中心性、聚类系数和节点度等确定参数来识别枢纽基因。同样,通过MatInspector程序确定关键转录调节因子。最后,使用ClueGO进行富集分析。

结果

结果显示,多巴胺受体D2、脑源性神经营养因子和多巴胺受体D4在已报道的ADHD基因中被识别为枢纽基因。同时,17种转录因子(TFs)被确定为这些枢纽基因的关键TFs。

结论

功能富集分析揭示了多巴胺调节和行为恐惧反应途径。在所选候选基因中,这些途径被认为在ADHD中起核心作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c789/7597701/542095e16744/IJPsy-62-400-g001.jpg

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