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TargetAntiAngio: A Sequence-Based Tool for the Prediction and Analysis of Anti-Angiogenic Peptides
Vishuda Laengsri1,2, Chanin Nantasenamat3, Nalini Schaduangrat4
1Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand. l.vishuda@gmail.com.
Abstract:
Cancer remains one of the major causes of death worldwide. Angiogenesis is crucial for the pathogenesis of various human diseases, especially solid tumors. The discovery of anti-angiogenic peptides is a promising therapeutic route for cancer treatment. Thus, reliably identifying anti-angiogenic peptides is extremely important for understanding their biophysical and biochemical properties that serve as the basis for the discovery of new anti-cancer drugs. This study aims to develop an efficient and interpretable computational model called TargetAntiAngio for predicting and characterizing anti-angiogenic peptides. TargetAntiAngio was developed using the random forest classifier in conjunction with various classes of peptide features. It was observed via an independent validation test that TargetAntiAngio can identify anti-angiogenic peptides with an average accuracy of 77.50% on an objective benchmark dataset. Comparisons demonstrated that TargetAntiAngio is superior to other existing methods. In addition, results revealed the following important characteristics of anti-angiogenic peptides: (i) disulfide bond forming Cys residues play an important role for inhibiting blood vessel proliferation; (ii) Cys located at the C-terminal domain can decrease endothelial formatting activity and suppress tumor growth; and (iii) Cyclic disulfide-rich peptides contribute to the inhibition of angiogenesis and cell migration, selectivity and stability. Finally, for the convenience of experimental scientists, the TargetAntiAngio web server was established and made freely available online.
Insights
Researchers developed TargetAntiAngio, a computational model that accurately predicts anti-angiogenic peptides, crucial for developing new cancer therapies. This tool identifies key peptide characteristics that inhibit tumor growth and blood vessel formation.
Area of Science:
- Biochemistry
- Computational Biology
- Oncology
Background:
- Angiogenesis, the formation of new blood vessels, is vital for solid tumor growth and a key target for cancer therapies.
- Identifying anti-angiogenic peptides is crucial for developing novel anti-cancer drugs and understanding their mechanisms.
- Existing methods for identifying anti-angiogenic peptides require improvement in efficiency and interpretability.
Purpose of the Study:
- To develop an efficient and interpretable computational model, TargetAntiAngio, for predicting and characterizing anti-angiogenic peptides.
- To leverage peptide features and machine learning for accurate anti-angiogenic peptide identification.
- To provide insights into the structural and functional characteristics of anti-angiogenic peptides.
Main Methods:
- Development of the TargetAntiAngio model using a random forest classifier.
- Integration of various classes of peptide features into the model.
- Validation using an independent benchmark dataset to assess predictive accuracy.
Main Results:
- TargetAntiAngio achieved an average accuracy of 77.50% in identifying anti-angiogenic peptides.
- The model demonstrated superior performance compared to existing anti-angiogenic peptide identification methods.
- Key characteristics of anti-angiogenic peptides were identified, including the role of cysteine residues and disulfide bonds.
Conclusions:
- TargetAntiAngio is an effective computational tool for predicting anti-angiogenic peptides.
- Disulfide bond forming Cys residues, particularly at the C-terminal domain, are important for inhibiting angiogenesis and tumor growth.
- Cyclic disulfide-rich peptides exhibit enhanced selectivity, stability, and anti-angiogenic properties, offering potential for cancer therapy.
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