iIL13Pred: improved prediction of IL-13 inducing peptides using popular machine learning classifiers.

BACKGROUND: Inflammatory mediators play havoc in several diseases including the novel Coronavirus disease 2019 (COVID-19) and generally correlate with the severity of the disease. Interleukin-13 (IL-13), is a pleiotropic cytokine that is known to be associated with airway inflammation in asthma and reactive airway diseases, in neoplastic and autoimmune diseases. Interestingly, the recent association of IL-13 with COVID-19 severity has sparked interest in this cytokine. Therefore characterization of new molecules which can regulate IL-13 induction might lead to novel therapeutics. RESULTS: Here, we present an improved prediction of IL-13-inducing peptides. The positive and negative datasets were obtained from a recent study (IL13Pred) and the Pfeature algorithm was used to compute features for the peptides. As compared to the state-of-the-art which used the regularization based feature selection technique (linear support vector classifier with the L1 penalty), we used a multivariate feature selection technique (minimum redundancy maximum relevance) to obtain non-redundant and highly relevant features. In the proposed study (improved IL-13 prediction (iIL13Pred)), the use of the mRMR feature selection method is instrumental in choosing the most discriminatory features of IL-13-inducing peptides with improved performance. We investigated seven common machine learning classifiers including Decision Tree, Gaussian Naïve Bayes, k-Nearest Neighbour, Logistic Regression, Support Vector Machine, Random Forest, and extreme gradient boosting to efficiently classify IL-13-inducing peptides. We report improved AUC, and MCC scores of 0.83 and 0.33 on validation data as compared to the current method. CONCLUSIONS: Extensive benchmarking experiments suggest that the proposed method (iIL13Pred) could provide improved performance metrics in terms of sensitivity, specificity, accuracy, the area under the curve - receiver operating characteristics (AUCROC) and Matthews correlation coefficient (MCC) than the existing state-of-the-art approach (IL13Pred) on the validation dataset and an external dataset comprising of experimentally validated IL-13-inducing peptides. Additionally, the experiments were performed with an increased number of experimentally validated training datasets to obtain a more robust model. A user-friendly web server ( www.soodlab.com/iil13pred ) is also designed to facilitate rapid screening of IL-13-inducing peptides.

Time Series Analysis of SARS-CoV-2 Genomes and Correlations among Highly Prevalent Mutations.

The efforts of the scientific community to tame the recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seem to have been diluted by the emergence of new viral strains. Therefore, it is imperative to understand the effect of mutations on viral evolution. We performed a time series analysis on 59,541 SARS-CoV-2 genomic sequences from around the world to gain insights into the kinetics of the mutations arising in the viral genomes. These 59,541 genomes were grouped according to month (January 2020 to March 2021) based on the collection date. Meta-analysis of these data led us to identify significant mutations in viral genomes. Pearson correlation of these mutations led us to the identification of 16 comutations. Among these comutations, some of the individual mutations have been shown to contribute to viral replication and fitness, suggesting a possible role of other unexplored mutations in viral evolution. We observed that the mutations 241C>T in the 5' untranslated region (UTR), 3037C>T in nsp3, 14408C>T in the RNA-dependent RNA polymerase (RdRp), and 23403A>G in spike are correlated with each other and were grouped in a single cluster by hierarchical clustering. These mutations have replaced the wild-type nucleotides in SARS-CoV-2 sequences. Additionally, we employed a suite of computational tools to investigate the effects of T85I (1059C>T), P323L (14408C>T), and Q57H (25563G>T) mutations in nsp2, RdRp, and the ORF3a protein of SARS-CoV-2, respectively. We observed that the mutations T85I and Q57H tend to be deleterious and destabilize the respective wild-type protein, whereas P323L in RdRp tends to be neutral and has a stabilizing effect. IMPORTANCE We performed a meta-analysis on SARS-CoV-2 genomes categorized by collection month and identified several significant mutations. Pearson correlation analysis of these significant mutations identified 16 comutations having absolute correlation coefficients of >0.4 and a frequency of >30% in the genomes used in this study. The correlation results were further validated by another statistical tool called hierarchical clustering, where mutations were grouped in clusters on the basis of their similarity. We identified several positive and negative correlations among comutations in SARS-CoV-2 isolates from around the world which might contribute to viral pathogenesis. The negative correlations among some of the mutations in SARS-CoV-2 identified in this study warrant further investigations. Further analysis of mutations such as T85I in nsp2 and Q57H in ORF3a protein revealed that these mutations tend to destabilize the protein relative to the wild type, whereas P323L in RdRp is neutral and has a stabilizing effect. Thus, we have identified several comutations which can be further characterized to gain insights into SARS-CoV-2 evolution.