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基于单核苷酸变异比例的抑郁患者和正常对照的遗传聚类。

Genetic clustering of depressed patients and normal controls based on single-nucleotide variant proportion.

机构信息

Robinson Research Institute, Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia; Mind and Brain Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia; College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia.

Discipline of Psychiatry, Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.

出版信息

J Affect Disord. 2018 Feb;227:450-454. doi: 10.1016/j.jad.2017.11.023. Epub 2017 Nov 10.

DOI:10.1016/j.jad.2017.11.023
PMID:29154167
Abstract

BACKGROUND

Genetic components play important roles in the susceptibility to major depressive disorder (MDD). The rapid development of sequencing technologies is allowing scientists to contribute new ideas for personalized medicine; thus, it is essential to design non-invasive genetic tests on sequencing data, which can help physicians diagnose and differentiate depressed patients and healthy individuals.

METHODS

We have recently proposed a genetic concept involving single-nucleotide variant proportion (SNVP) in genes to study MDD. Using this approach, we investigated combinations of distance metrics and hierarchical clustering criteria for genetic clustering of depressed patients and ethnically matched controls.

RESULTS

We analysed clustering results of 25 human subjects based on their SNVPs in 46 newly discovered candidate genes.

CONCLUSIONS

According to our findings, we recommend Canberra metric with Ward's method to be used in hierarchical clustering of depressed and normal individuals. Futures studies are needed to advance this line of research validating our approach in larger datasets, those may also be allow the investigation of MDD subtypes.

LIMITATIONS

High quality sequencing costs limited our ability to obtain larger datasets.

摘要

背景

遗传因素在重度抑郁症(MDD)易感性中起着重要作用。测序技术的快速发展使科学家们能够为个性化医学提供新的思路;因此,设计基于测序数据的非侵入性遗传测试至关重要,这有助于医生诊断和区分抑郁患者和健康个体。

方法

我们最近提出了一个涉及基因中单核苷酸变异比例(SNVP)的遗传概念,以研究 MDD。使用这种方法,我们研究了距离度量和层次聚类标准的组合,以对抑郁患者和种族匹配的对照组进行遗传聚类。

结果

我们根据 25 个人的 SNVPs 在 46 个新发现的候选基因中的分析结果进行了聚类。

结论

根据我们的发现,我们建议在抑郁和正常个体的层次聚类中使用堪培拉度量和 Ward 方法。需要进一步的研究来推进这一研究领域,在更大的数据集上验证我们的方法,这也可能允许对 MDD 亚型进行研究。

局限性

高质量测序的成本限制了我们获得更大数据集的能力。

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