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差异共表达和调控分析揭示了重度抑郁症和亚综合征症状性抑郁症背后的不同机制。

Differential co-expression and regulation analyses reveal different mechanisms underlying major depressive disorder and subsyndromal symptomatic depression.

作者信息

Xu Fan, Yang Jing, Chen Jin, Wu Qingyuan, Gong Wei, Zhang Jianguo, Shao Weihua, Mu Jun, Yang Deyu, Yang Yongtao, Li Zhiwei, Xie Peng

机构信息

Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, China.

Institute of Neuroscience, Chongqing Medical University, and Chongqing Key Laboratory of Neurobiology, Chongqing, China.

出版信息

BMC Bioinformatics. 2015 Apr 3;16:112. doi: 10.1186/s12859-015-0543-y.

DOI:10.1186/s12859-015-0543-y
PMID:25880836
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4434877/
Abstract

BACKGROUND

Recent depression research has revealed a growing awareness of how to best classify depression into depressive subtypes. Appropriately subtyping depression can lead to identification of subtypes that are more responsive to current pharmacological treatment and aid in separating out depressed patients in which current antidepressants are not particularly effective. Differential co-expression analysis (DCEA) and differential regulation analysis (DRA) were applied to compare the transcriptomic profiles of peripheral blood lymphocytes from patients with two depressive subtypes: major depressive disorder (MDD) and subsyndromal symptomatic depression (SSD).

RESULTS

Six differentially regulated genes (DRGs) (FOSL1, SRF, JUN, TFAP4, SOX9, and HLF) and 16 transcription factor-to-target differentially co-expressed gene links or pairs (TF2target DCLs) appear to be the key differential factors in MDD; in contrast, one DRG (PATZ1) and eight TF2target DCLs appear to be the key differential factors in SSD. There was no overlap between the MDD target genes and SSD target genes. Venlafaxine (Efexor™, Effexor™) appears to have a significant effect on the gene expression profile of MDD patients but no significant effect on the gene expression profile of SSD patients.

CONCLUSION

DCEA and DRA revealed no apparent similarities between the differential regulatory processes underlying MDD and SSD. This bioinformatic analysis may provide novel insights that can support future antidepressant R&D efforts.

摘要

背景

近期的抑郁症研究表明，人们越来越意识到如何将抑郁症最佳地分类为抑郁亚型。对抑郁症进行恰当的亚型分类能够识别出对当前药物治疗反应更佳的亚型，并有助于区分出当前抗抑郁药效果不佳的抑郁症患者。应用差异共表达分析（DCEA）和差异调控分析（DRA）来比较两种抑郁亚型患者外周血淋巴细胞的转录组谱，这两种抑郁亚型分别为重度抑郁症（MDD）和亚综合征症状性抑郁症（SSD）。

结果

六个差异调控基因（DRGs）（FOSL1、SRF、JUN、TFAP4、SOX9和HLF）以及16个转录因子-靶标差异共表达基因链接或配对（TF2target DCLs）似乎是MDD中的关键差异因素；相比之下，一个DRG（PATZ1）和八个TF2target DCLs似乎是SSD中的关键差异因素。MDD靶基因和SSD靶基因之间没有重叠。文拉法辛（怡诺思™、Effexor™）似乎对MDD患者的基因表达谱有显著影响，但对SSD患者的基因表达谱没有显著影响。

结论

DCEA和DRA显示，MDD和SSD潜在的差异调控过程之间没有明显相似性。这种生物信息学分析可能提供新的见解，以支持未来的抗抑郁药物研发工作。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/083d/4434877/1eb6ce1c2d71/12859_2015_543_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/083d/4434877/cef612652bd3/12859_2015_543_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/083d/4434877/7c3baecf7958/12859_2015_543_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/083d/4434877/639fc1ac07b8/12859_2015_543_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/083d/4434877/1eb6ce1c2d71/12859_2015_543_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/083d/4434877/cef612652bd3/12859_2015_543_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/083d/4434877/7c3baecf7958/12859_2015_543_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/083d/4434877/639fc1ac07b8/12859_2015_543_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/083d/4434877/1eb6ce1c2d71/12859_2015_543_Fig4_HTML.jpg

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