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AbstractpiwiRNA is a kind of non-coding RNA (ncRNA) that cannot be translated into proteins. It helps in understanding the study of gametes generation and regulation of gene expression over both transcriptional and post-transcriptional levels. piwiRNA has the function of instructing deadenylation, animal fertility, silencing transposons, fighting viruses, and regulating endogenous genes. Due to the great significance of piwiRNA, prediction of piwiRNA is essential for crucial cellular functions. Several predictors were established for prediction of piwiRNA. However, improving the prediction of piwiRNA is highly desirable. In the current study, we developed a more promising predictor named, BLP-piwiRNA. The features are explored by reverse complement k-mer, gapped-k-mer composition, and k-mer composition. The feature set of all descriptors is fused and the best features are selected by cascade and relief feature selection strategies. The best feature sets are provided to random forest (RF), deep neural network (DNN), and support vector machine (SVM). The models validation are examined by 10-fold test. DNN with optimal features of Cascade feature selection approach secured the highest prediction results. The results illustrate that BLP-piwiRNA effectively outperforms the existing studies. The proposed approach would be beneficial for both research community and drug development industry. BLP-piwiRNA would serve as novel biomarkers and therapeutic targets for tumor diagnostics and treatment.Communicated by Ramaswamy H. Sarma