Mining key circadian biomarkers for major depressive disorder by integrating bioinformatics and machine learning

Jun 14, 2024Aging

Identifying important daily rhythm markers linked to major depression using computer analysis and machine learning

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Four key circadian rhythm genes were identified that could effectively distinguish MDD samples from controls.

The identified genes are ABCC2, APP, HK2, and RORA.
These genes are significantly enriched in pathways related to circadian rhythms.
Strong correlations were observed between these genes and immune cell infiltration.
Drug target prediction indicates that small molecules like melatonin and escitalopram may interact with these circadian rhythm proteins.
The findings suggest that disruptions in circadian rhythms may play a role in the development of major depressive disorder.

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OBJECTIVE: This study aimed to identify key clock genes closely associated with major depressive disorder (MDD) using bioinformatics and machine learning approaches.

METHODS: Gene expression data of 128 MDD patients and 64 healthy controls from blood samples were obtained. Differentially expressed were identified and weighted gene co-expression network analysis (WGCNA) was first performed to screen MDD-related key genes. These genes were then intersected with 1475 known circadian rhythm genes to identify circadian rhythm genes associated with MDD. Finally, multiple machine learning algorithms were applied for further selection, to determine the most critical 4 circadian rhythm biomarkers.

RESULTS: Four key circadian rhythm genes (ABCC2, APP, HK2 and RORA) were identified that could effectively distinguish MDD samples from controls. These genes were significantly enriched in circadian pathways and showed strong correlations with immune cell infiltration. Drug target prediction suggested that small molecules like melatonin and escitalopram may target these circadian rhythm proteins.

CONCLUSION: This study revealed discovered 4 key circadian rhythm genes closely associated with MDD, which may serve as diagnostic biomarkers and therapeutic targets. The findings highlight the important roles of circadian disruptions in the pathogenesis of MDD, providing new insights for precision diagnosis and targeted treatment of MDD.

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Mining key circadian biomarkers for major depressive disorder by integrating bioinformatics and machine learning

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