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Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
A novel approach to select differential pathways associated with hypertrophic cardiomyopathy based on gene
Xiao-Min Chen1, Ming-Jun Feng1, Cai-Jie Shen2
1Department of Cardiology, Ningbo First Hospital, Ningbo, Zhejiang 315000, P.R. China.
Insights
This study introduces a new gene co-expression analysis method to identify significant pathways in hypertrophic cardiomyopathy (HCM). The novel approach identified more pathways than traditional methods, potentially revealing new therapeutic targets for HCM.
Area of Science:
- Cardiovascular Biology
- Systems Biology
- Bioinformatics
Background:
- Hypertrophic cardiomyopathy (HCM) is a complex genetic heart disease.
- Identifying key biological pathways is crucial for understanding HCM pathogenesis and developing treatments.
Purpose of the Study:
- To develop and validate a novel gene co-expression analysis method for identifying significant pathways in human hypertrophic cardiomyopathy (HCM).
- To compare the efficacy of the novel co-expression method against traditional pathway enrichment analysis.
Main Methods:
- Utilized a microarray dataset (E-GEOD-36961) for HCM patients.
- Employed an empirical Bayes method to construct gene co-expression networks and assigned pathway weights.
- Screened informative pathways using the Reactome database and differential pathway extraction based on a weight threshold.
Main Results:
- Identified 1,074 informative pathways and assigned weight values.
- Extracted 447 differential pathways, including actin folding by CCT/TRiC, purine ribonucleoside monophosphate biosynthesis, and ubiquinol biosynthesis.
- The co-expression approach yielded a greater number of pathways compared to traditional enrichment analysis.
Conclusions:
- The developed co-expression method is a feasible approach for predicting marker pathways in HCM.
- Identified pathways like actin folding and purine biosynthesis may elucidate HCM molecular mechanisms.
- These findings offer potential novel therapeutic strategies for hypertrophic cardiomyopathy.
Abstract:
The present study was designed to develop a novel method for identifying significant pathways associated with human hypertrophic cardiomyopathy (HCM), based on gene co‑expression analysis. The microarray dataset associated with HCM (E‑GEOD‑36961) was obtained from the European Molecular Biology Laboratory‑European Bioinformatics Institute database. Informative pathways were selected based on the Reactome pathway database and screening treatments. An empirical Bayes method was utilized to construct co‑expression networks for informative pathways, and a weight value was assigned to each pathway. Differential pathways were extracted based on weight threshold, which was calculated using a random model. In order to assess whether the co‑expression method was feasible, it was compared with traditional pathway enrichment analysis of differentially expressed genes, which were identified using the significance analysis of microarrays package. A total of 1,074 informative pathways were screened out for subsequent investigations and their weight values were also obtained. According to the threshold of weight value of 0.01057, 447 differential pathways, including folding of actin by chaperonin containing T‑complex protein 1 (CCT)/T‑complex protein 1 ring complex (TRiC), purine ribonucleoside monophosphate biosynthesis and ubiquinol biosynthesis, were obtained. Compared with traditional pathway enrichment analysis, the number of pathways obtained from the co‑expression approach was increased. The results of the present study demonstrated that this method may be useful to predict marker pathways for HCM. The pathways of folding of actin by CCT/TRiC and purine ribonucleoside monophosphate biosynthesis may provide evidence of the underlying molecular mechanisms of HCM, and offer novel therapeutic directions for HCM.
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