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Identifying Human SIRT1 Substrates by Integrating Heterogeneous Information from Various Sources
Zichao Zhai1, Ming Tang2, Yue Yang1
1Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
Scientific Reports
|July 6, 2017
Summary
This study introduces a new computational method to identify SIRT1 substrates, crucial proteins involved in acetylation. The approach integrates sequence and functional features, significantly improving prediction accuracy for biological research.
Area of Science:
- Biochemistry
- Computational Biology
- Molecular Biology
Background:
- Protein acetylation is a vital post-translational modification impacting biological activities.
- Sirtuin 1 (SIRT1), a Class III HDAC, plays a key role in acetylation, but its function is difficult to elucidate due to a limited number of known substrates.
Purpose of the Study:
- To develop a novel computational method for screening and identifying SIRT1 substrates.
- To enhance the accuracy of SIRT1 substrate prediction by incorporating diverse protein features.
Main Methods:
- A Support Vector Machine (SVM) based computational approach was designed.
- The method integrates both primary protein sequence and functional features for prediction.
- A manually curated dataset was used for training and validation.
Main Results:
- Integrating functional features improved the Matthews correlation coefficient (MCC) from 0.10 to 0.65.
- The developed classifier demonstrated high effectiveness in identifying SIRT1 substrates.
- Validation using an independent dataset and biological experiments confirmed the method's accuracy.
Conclusions:
- The novel computational method effectively identifies SIRT1 substrates, aiding in understanding SIRT1's biological roles.
- The tool provides a valuable resource for filtering candidate substrates for further experimental research.
- An online prediction tool is available to support the scientific community.

