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Microprotein Dysregulation in the Serum of Patients with Atrial Fibrillation
Zheng Zhang1, Tao Tian2, Ni Pan1
1School of Life Sciences and Hubei Key Laboratory of Genetic Regulation and Integrative Biology, Central China Normal University, Wuhan, Hubei 430079, People's Republic of China.
Abstract:
The incidence rate of atrial fibrillation (AF) has stayed at a high level in recent years. Despite the intensive efforts to study the pathologic changes of AF, the molecular mechanism of disease development remains unclarified. Microproteins are ribosomally translated gene products from small open reading frames (sORFs) and are found to play crucial biological functions, while remain rare attention and indistinct in AF study. In this work, we recruited 65 AF patients and 65 healthy subjects for microproteomic profiling. By differential analysis and cross-validation between independent datasets, a total of 4 microproteins were identified as significantly different, including 3 annotated ones and 1 novel one. Additionally, we established a diagnostic model with either microproteins or global proteins by machine learning methods and found the model with microproteins achieved comparable and excellent performance as that with global proteins. Our results confirmed the abnormal expression of microproteins in AF and may provide new perspectives on the mechanism study of AF.
Insights
Researchers identified 4 microproteins with abnormal expression in atrial fibrillation (AF) patients. A diagnostic model using these microproteins showed excellent performance, offering new insights into AF mechanisms.
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiology
Background:
- Atrial fibrillation (AF) incidence remains high, with its molecular mechanisms poorly understood.
- Microproteins, translated from small open reading frames (sORFs), have critical biological roles but are understudied in AF.
- Existing research on AF pathology has not fully elucidated the underlying molecular drivers.
Purpose of the Study:
- To investigate the role of microproteins in the molecular mechanism of atrial fibrillation.
- To identify differentially expressed microproteins in AF patients compared to healthy individuals.
- To develop and evaluate a diagnostic model for AF using microprotein expression profiles.
Main Methods:
- Microproteomic profiling of 65 AF patients and 65 healthy subjects.
- Differential analysis and cross-validation of microprotein expression data.
- Machine learning-based diagnostic model development using microproteins and global proteins.
Main Results:
- Four microproteins, including one novel, showed significantly different expression levels in AF patients.
- A diagnostic model based on microprotein expression achieved performance comparable to a model using global proteins.
- Abnormal microprotein expression is confirmed in the context of atrial fibrillation.
Conclusions:
- Microproteins represent a novel class of biomarkers and potential therapeutic targets for atrial fibrillation.
- The findings suggest that microproteins play a significant role in AF pathogenesis.
- This study opens new avenues for understanding the molecular basis of atrial fibrillation.
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