Background Angiogenesis inhibition research is a cutting edge area in angiogenesis-dependent disease therapy, especially in cancer therapy. Recently, studies on anti-angiogenic peptides have provided promising results in the field of cancer treatment. Methods A non-redundant dataset of 135 anti-angiogenic peptides (positive instances) and 135 non anti-angiogenic peptides (negative instances) was used in this study. Also, 20% of each class were selected to construct an independent test dataset (see Additional files 1, 2). We proposed an effective machine learning based R package (AntAngioCOOL) to predict anti-angiogenic peptides. We have examined more than 200 different classifiers to build an efficient predictor. Also, more than 17,000 features were extracted to encode the peptides. Results Finally, more than 2000 informative features were selected to train the classifiers for detecting anti-angiogenic peptides. AntAngioCOOL includes three different models that can be selected by the user for different purposes; it is the most sensitive, most specific and most accurate. According to the obtained results AntAngioCOOL can effectively suggest anti-angiogenic peptides; this tool achieved sensitivity of 88%, specificity of 77% and accuracy of 75% on the independent test set. AntAngioCOOL can be accessed at https://cran.r-project.org/. Conclusions Only 2% of the extracted descriptors were used to build the predictor models. The results revealed that physico-chemical profile is the most important feature type in predicting anti-angiogenic peptides. Also, atomic profile and PseAAC are the other important features.

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