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Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein
Published on: June 30, 2019
Comprehensive bioinformatics analysis reveals kinase activity profiling associated with heart failure
Zhen Zhang1, Saisai Tian1, Chennan Wu1
1School of Pharmacy, Second Military Medical University, Shanghai, China.
Abstract:
Heart failure is a complex clinical syndrome originating from cardiac injury, which leads to considerable morbidity and mortality. Among the dynamic molecular adaptations occurring in heart failure development, aggravation of the disease is often attributed to global or local abnormality of the kinase. Therefore, the overall monitoring of kinase activity is indispensable. In this study, a bioinformatics analysis method was developed to conduct deep mining of transcriptome and phosphoproteome in failing heart tissue. A total of 982 differentially expressed genes and 9781 phosphorylation sites on 3252 proteins were identified. Via upstream regulator relations and kinase-substrate relations, a dendrogram of kinases can be constructed to monitor its abnormality. The results show that, on the dendrogram, the distribution of kinases demonstrated complex kinase activity changes and certain rules that occur during heart failure. Finally, we also identified the hub kinases in heart failure and verified the expression of these kinases by reverse-transcription polymerase chain reaction and Western blot analysis. In conclusion, for the first time, we have systematically analyzed the differences in kinases during heart failure and provided an unprecedented breadth of multi-omics data. These results can bring about a sufficient data foundation and novel research perspectives.
Insights
This study developed a bioinformatics method to analyze kinase activity in heart failure. It identified key kinases and their complex changes, offering new research perspectives for this condition.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Bioinformatics
Background:
- Heart failure is a complex syndrome with significant morbidity and mortality.
- Kinase abnormalities are implicated in the progression of heart failure.
- Monitoring kinase activity is crucial for understanding and managing heart failure.
Purpose of the Study:
- To develop a bioinformatics method for deep mining of multi-omics data in heart failure.
- To systematically analyze kinase activity and identify key kinases in heart failure.
- To provide a comprehensive dataset and novel research perspectives for heart failure.
Main Methods:
- Bioinformatics analysis of transcriptome and phosphoproteome data from failing heart tissue.
- Identification of differentially expressed genes and phosphorylation sites.
- Construction of kinase dendrograms using upstream regulator and kinase-substrate relations.
- Validation of hub kinase expression using reverse-transcription polymerase chain reaction and Western blot analysis.
Main Results:
- 982 differentially expressed genes and 9781 phosphorylation sites on 3252 proteins were identified.
- Complex kinase activity changes and specific patterns were observed in heart failure.
- Hub kinases critical to heart failure were identified and expression validated.
Conclusions:
- A novel bioinformatics approach systematically analyzed kinase differences in heart failure.
- This study provides an unprecedented breadth of multi-omics data for heart failure research.
- The findings offer a robust data foundation and novel perspectives for future heart failure studies.
