A method for predicting linear and conformational B-cell epitopes in an antigen from its primary sequence.

B-cell is an essential component of the immune system that plays a vital role in providing the immune response against any pathogenic infection by producing antibodies. Existing methods either predict linear or conformational B-cell epitopes in an antigen. In this study, a single method was developed for predicting both types (linear/conformational) of B-cell epitopes. The dataset used in this study contains 3875 B-cell epitopes and 3996 non-B-cell epitopes, where B-cell epitopes consist of both linear and conformational B-cell epitopes. Our primary analysis indicates that certain residues (like Asp, Glu, Lys, and Asn) are more prominent in B-cell epitopes. We developed machine-learning based methods using different types of sequence composition and achieved the highest AUROC of 0.80 using dipeptide composition. In addition, models were developed on selected features, but no further improvement was observed. Our similarity-based method implemented using BLAST shows a high probability of correct prediction with poor sensitivity. Finally, we developed a hybrid model that combines alignment-free (dipeptide based random forest model) and alignment-based (BLAST-based similarity) models. Our hybrid model attained a maximum AUROC of 0.83 with an MCC of 0.49 on the independent dataset. Our hybrid model performs better than existing methods on an independent dataset used in this study. All models were trained and tested on 80 % of the data using a cross-validation technique, and the final model was evaluated on 20 % of the data, called an independent or validation dataset. A webserver and standalone package named "CLBTope" has been developed for predicting, designing, and scanning B-cell epitopes in an antigen sequence available at (https://webs.iiitd.edu.in/raghava/clbtope/).

A random forest model for predicting exosomal proteins using evolutionary information and motifs.

Non-invasive diagnostics and therapies are crucial to prevent patients from undergoing painful procedures. Exosomal proteins can serve as important biomarkers for such advancements. In this study, we attempted to build a model to predict exosomal proteins. All models are trained, tested, and evaluated on a non-redundant dataset comprising 2831 exosomal and 2831 non-exosomal proteins, where no two proteins have more than 40% similarity. Initially, the standard similarity-based method Basic Local Alignment Search Tool (BLAST) was used to predict exosomal proteins, which failed due to low-level similarity in the dataset. To overcome this challenge, machine learning (ML) based models were developed using compositional and evolutionary features of proteins achieving an area under the receiver operating characteristics (AUROC) of 0.73. Our analysis also indicated that exosomal proteins have a variety of sequence-based motifs which can be used to predict exosomal proteins. Hence, we developed a hybrid method combining motif-based and ML-based approaches for predicting exosomal proteins, achieving a maximum AUROC of 0.85 and MCC of 0.56 on an independent dataset. This hybrid model performs better than presently available methods when assessed on an independent dataset. A web server and a standalone software ExoProPred (https://webs.iiitd.edu.in/raghava/exopropred/) have been created to help scientists predict and discover exosomal proteins and find functional motifs present in them.

ChAlPred: A web server for prediction of allergenicity of chemical compounds.

BACKGROUND: Allergy is the abrupt reaction of the immune system that may occur after the exposure to allergens such as proteins, peptides, or chemicals. In the past, various methods have been generated for predicting allergenicity of proteins and peptides. In contrast, there is no method that can predict allergenic potential of chemicals. In this paper, we described a method ChAlPred developed for predicting chemical allergens as well as for designing chemical analogs with desired allergenicity. METHOD: In this study, we have used 403 allergenic and 1074 non-allergenic chemical compounds obtained from IEDB database. The PaDEL software was used to compute the molecular descriptors of the chemical compounds to develop different prediction models. All the models were trained and tested on the 80% training data and evaluated on the 20% validation data using the 2D, 3D and FP descriptors. RESULTS: In this study, we have developed different prediction models using several machine learning approaches. It was observed that the Random Forest based model developed using hybrid descriptors performed the best, and achieved the maximum accuracy of 83.39% and AUC of 0.93 on validation dataset. The fingerprint analysis of the dataset indicates that certain chemical fingerprints are more abundant in allergens that include PubChemFP129 and GraphFP1014. We have also predicted allergenicity potential of FDA-approved drugs using our best model and identified the drugs causing allergic symptoms (e.g., Cefuroxime, Spironolactone, Tioconazole). Our results agreed with allergenicity of these drugs reported in literature. CONCLUSIONS: To aid the research community, we developed a smart-device compatible web server ChAlPred (https://webs.iiitd.edu.in/raghava/chalpred/) that allows to predict and design the chemicals with allergenic properties.

Computer-aided prediction of inhibitors against STAT3 for managing COVID-19 associated cytokine storm.

BACKGROUND: Proinflammatory cytokines are correlated with the severity of disease in patients with COVID-19. IL6-mediated activation of STAT3 proliferates proinflammatory responses that lead to cytokine storm promotion. Thus, STAT3 inhibitors may play a crucial role in managing the COVID-19 pathogenesis. The present study discusses a method for predicting inhibitors against the STAT3 signaling pathway. METHOD: The main dataset comprises 1565 STAT3 inhibitors and 1671 non-inhibitors used for training, testing, and evaluation of models. A number of machine learning classifiers have been implemented to develop the models. RESULTS: The outcomes of the data analysis show that rings and aromatic groups are significantly abundant in STAT3 inhibitors compared to non-inhibitors. First, we developed models using 2-D and 3-D chemical descriptors and achieved a maximum AUC of 0.84 and 0.73, respectively. Second, fingerprints are used to build predictive models and achieved 0.86 AUC with an accuracy of 78.70% on the validation dataset. Finally, models were developed using hybrid descriptors, which achieved a maximum of 0.87 AUC with 78.55% accuracy on the validation dataset. CONCLUSION: We used the best model to identify STAT3 inhibitors in FDA-approved drugs and found few drugs (e.g., Tamoxifen and Perindopril) to manage the cytokine storm in COVID-19 patients. A webserver "STAT3In" (https://webs.iiitd.edu.in/raghava/stat3in/) has been developed to predict and design STAT3 inhibitors.