StackDPPred: Multiclass prediction of defensin peptides using stacked ensemble learning with optimized features.

Host defense or antimicrobial peptides (AMPs) are promising candidates for protecting host against microbial pathogens for example bacteria, virus, fungi, yeast. Defensins are the type of AMPs that act as potential therapeutic drug agent and perform vital role in various biological process. Conventional Experiments to identify defensin peptides (DPs) are time consuming and expensive. Thus, the shortcomings of wet lab experiments are leveraged by computational methods to accurately predict the functional types of DPs. In this paper, we aim to propose a novel multi-class ensemble-based prediction model called StackDPPred for identifying the properties of DPs. The peptide sequences are encoded using split amino acid composition (SAAC), segmented position specific scoring matrix (SegPSSM), histogram of oriented gradients-based PSSM (HOGPSSM) and feature extraction based graphical and statistical (FEGS) descriptors. Next, principal component analysis (PCA) is used to select the best subset of attributes. After that, the optimized features are fed into single machine learning and stacking-based ensemble classifiers. Furthermore, the ablation study demonstrates the robustness and efficacy of the stacking approach using reduced features for predicting DPs and their families. The proposed StackDPPred method improves the overall accuracy by 13.41% and 7.62% compared to existing DPs predictors iDPF-PseRAAC and iDEF-PseRAAC, respectively on validation test. Additionally, we applied the local interpretable model-agnostic explanations (LIME) algorithm to understand the contribution of selected features to the overall prediction. We believe, StackDPPred could serve as a valuable tool accelerating the screening of large-scale DPs and peptide-based drug discovery process.

PLMACPred prediction of anticancer peptides based on protein language model and wavelet denoising transformation.

Anticancer peptides (ACPs) perform a promising role in discovering anti-cancer drugs. The growing research on ACPs as therapeutic agent is increasing due to its minimal side effects. However, identifying novel ACPs using wet-lab experiments are generally time-consuming, labor-intensive, and expensive. Leveraging computational methods for fast and accurate prediction of ACPs would harness the drug discovery process. Herein, a machine learning-based predictor, called PLMACPred, is developed for identifying ACPs from peptide sequence only. PLMACPred adopted a set of encoding schemes representing evolutionary-property, composition-property, and protein language model (PLM), i.e., evolutionary scale modeling (ESM-2)- and ProtT5-based embedding to encode peptides. Then, two-dimensional (2D) wavelet denoising (WD) was employed to remove the noise from extracted features. Finally, ensemble-based cascade deep forest (CDF) model was developed to identify ACP. PLMACPred model attained superior performance on all three benchmark datasets, namely, ACPmain, ACPAlter, and ACP740 over tenfold cross validation and independent dataset. PLMACPred outperformed the existing models and improved the prediction accuracy by 18.53%, 2.4%, 7.59% on ACPmain, ACPalter, ACP740 dataset, respectively. We showed that embedding from ProtT5 and ESM-2 was capable of capturing better contextual information from the entire sequence than the other encoding schemes for ACP prediction. For the explainability of proposed model, SHAP (SHapley Additive exPlanations) method was used to analyze the feature effect on the ACP prediction. A list of novel sequence motifs was proposed from the ACP sequence using MEME suites. We believe, PLMACPred will support in accelerating the discovery of novel ACPs as well as other activities of microbial peptides.

iMRSAPred: Improved Prediction of Anti-MRSA Peptides Using Physicochemical and Pairwise Contact-Energy Properties of Amino Acids.

Methicillin-resistant Staphylococcus aureus (MRSA) is a growing concern for human lives worldwide. Anti-MRSA peptides act as potential antibiotic agents and play significant role to combat MRSA infection. Traditional laboratory-based methods for annotating Anti-MRSA peptides are although precise but quite challenging, costly, and time-consuming. Therefore, computational methods capable of identifying Anti-MRSA peptides accelerate the drug designing process for treating bacterial infections. In this study, we developed a novel sequence-based predictor "iMRSAPred" for screening Anti-MRSA peptides by incorporating energy estimation and physiochemical and sequential information. We successfully resolved the skewed imbalance phenomena by using synthetic minority oversampling technique plus Tomek link (SMOTETomek) algorithm. Furthermore, the Shapley additive explanation method was leveraged to analyze the impact of top-ranked features in the prediction task. We evaluated multiple machine learning algorithms, i.e., CatBoost, Cascade Deep Forest, Kernel and Tree Boosting, support vector machine, and HistGBoost classifiers by 10-fold cross-validation and independent testing. The proposed iMRSAPred method significantly improved the overall performance in terms of accuracy and Matthew's correlation coefficient (MCC) by 5.45 and 0.083%, respectively, on the training data set. On the independent data set, iMRSAPred improved accuracy and MCC by 3.98 and 0.055%, respectively. We believe that the proposed method would be useful in large-scale Anti-MRSA peptide prediction and provide insights into other bioactive peptides.