Strategic pathway analysis for dual management of epilepsy and comorbid depression: a systems biology perspective.

In silico pharmacology Pub Date : 2024-04-30 eCollection Date: 2024-01-01 DOI:10.1007/s40203-024-00208-1
Arvinder Kaur, Raji, Varinder Verma, Rajesh Kumar Goel
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Abstract

Depression is a common psychiatric comorbidity among patients with epilepsy (PWE), affecting more than a third of PWE. Management of depression may improve quality of life of epileptic patients. Unfortunately, available antidepressants worsen epilepsy by reducing the seizure threshold. This situation demands search of new safer target for combined directorate of epilepsy and comorbid depression. A system biology approach may be useful to find novel pathways/markers for the cure of both epilepsy and associated depression via analyzing available genomic and proteomic information. Hence, the system biology approach using curated 64 seed genes involved in temporal lobe epilepsy and mental depression was applied. The interplay of 600 potential proteins was revealed by the Disease Module Detection (DIAMOnD) Algorithm for the treatment of both epilepsy and comorbid depression using these seed genes. The gene enrichment analysis of seed and diamond genes through DAVID suggested 95 pathways. Selected pathways were refined based on their syn or anti role in epilepsy and depression. In conclusion, total 8 pathways and 27 DIAMOnD genes/proteins were finally deduced as potential new targets for modulation of selected pathways to manage epilepsy and comorbid depression.

Supplementary information: The online version contains supplementary material available at 10.1007/s40203-024-00208-1.

癫痫和合并抑郁症双重管理的战略路径分析:系统生物学视角。
抑郁症是癫痫患者(PWE)中常见的精神并发症,影响着三分之一以上的癫痫患者。治疗抑郁症可改善癫痫患者的生活质量。遗憾的是,现有的抗抑郁药会降低癫痫发作阈值,从而使癫痫恶化。这种情况要求寻找新的更安全的靶点,以综合控制癫痫和合并抑郁症。通过分析现有的基因组和蛋白质组信息,系统生物学方法可能有助于找到治疗癫痫和相关抑郁症的新通路/标记。因此,我们采用了系统生物学方法,使用了与颞叶癫痫和精神抑郁有关的 64 个经过策划的种子基因。疾病模块检测(DIAMOnD)算法揭示了 600 个潜在蛋白质的相互作用,从而利用这些种子基因治疗癫痫和合并抑郁症。通过 DAVID 对种子基因和钻石基因进行的基因富集分析提出了 95 条通路。根据这些通路在癫痫和抑郁症中的同步或反作用,对所选通路进行了细化。最后,共推导出 8 条通路和 27 个 DIAMOnD 基因/蛋白质,作为调节所选通路以控制癫痫和合并抑郁症的潜在新靶点:在线版本包含补充材料,可查阅 10.1007/s40203-024-00208-1。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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