MOESM1 of Influence of commercial inactivated yeast derivatives on the survival of probiotic bacterium Lactobacillus rhamnosus HN001 in an acidic environment

Additional file 1: Figure S1. Viability of S. cerevisiae EC-1118 when co-incubated with L. rhamnosus HN001 at pH 3.0. Cell counts are the mean values of triplicate experiments (n = 3), with error bars representing the standard deviation of the mean values

Structural Analysis and Prediction of Hematotoxicity Using Deep Learning Approaches

Hematotoxicity has been becoming a serious but overlooked toxicity in drug discovery. However, only a few in silico models have been reported for the prediction of hematotoxicity. In this study, we constructed a high-quality dataset comprising 759 hematotoxic compounds and 1623 nonhematotoxic compounds and then established a series of classification models based on a combination of seven machine learning (ML) algorithms and nine molecular representations. The results based on two data partitioning strategies and applicability domain (AD) analysis illustrate that the best prediction model based on Attentive FP yielded a balanced accuracy (BA) of 72.6%, an area under the receiver operating characteristic curve (AUC) value of 76.8% for the validation set, and a BA of 69.2%, an AUC of 75.9% for the test set. In addition, compared with existing filtering rules and models, our model achieved the highest BA value of 67.5% for the external validation set. Additionally, the shapley additive explanation (SHAP) and atom heatmap approaches were utilized to discover the important features and structural fragments related to hematotoxicity, which could offer helpful tips to detect undesired positive substances. Furthermore, matched molecular pair analysis (MMPA) and representative substructure derivation technique were employed to further characterize and investigate the transformation principles and distinctive structural features of hematotoxic chemicals. We believe that the novel graph-based deep learning algorithms and insightful interpretation presented in this study can be used as a trustworthy and effective tool to assess hematotoxicity in the development of new drugs

Structural Analysis and Prediction of Hematotoxicity Using Deep Learning Approaches

Hematotoxicity has been becoming a serious but overlooked toxicity in drug discovery. However, only a few in silico models have been reported for the prediction of hematotoxicity. In this study, we constructed a high-quality dataset comprising 759 hematotoxic compounds and 1623 nonhematotoxic compounds and then established a series of classification models based on a combination of seven machine learning (ML) algorithms and nine molecular representations. The results based on two data partitioning strategies and applicability domain (AD) analysis illustrate that the best prediction model based on Attentive FP yielded a balanced accuracy (BA) of 72.6%, an area under the receiver operating characteristic curve (AUC) value of 76.8% for the validation set, and a BA of 69.2%, an AUC of 75.9% for the test set. In addition, compared with existing filtering rules and models, our model achieved the highest BA value of 67.5% for the external validation set. Additionally, the shapley additive explanation (SHAP) and atom heatmap approaches were utilized to discover the important features and structural fragments related to hematotoxicity, which could offer helpful tips to detect undesired positive substances. Furthermore, matched molecular pair analysis (MMPA) and representative substructure derivation technique were employed to further characterize and investigate the transformation principles and distinctive structural features of hematotoxic chemicals. We believe that the novel graph-based deep learning algorithms and insightful interpretation presented in this study can be used as a trustworthy and effective tool to assess hematotoxicity in the development of new drugs

PyDPI: Freely Available Python Package for Chemoinformatics, Bioinformatics, and Chemogenomics Studies

The rapidly increasing amount of publicly available data in biology and chemistry enables researchers to revisit interaction problems by systematic integration and analysis of heterogeneous data. Herein, we developed a comprehensive python package to emphasize the integration of chemoinformatics and bioinformatics into a molecular informatics platform for drug discovery. PyDPI (drug–protein interaction with Python) is a powerful python toolkit for computing commonly used structural and physicochemical features of proteins and peptides from amino acid sequences, molecular descriptors of drug molecules from their topology, and protein–protein interaction and protein–ligand interaction descriptors. It computes 6 protein feature groups composed of 14 features that include 52 descriptor types and 9890 descriptors, 9 drug feature groups composed of 13 descriptor types that include 615 descriptors. In addition, it provides seven types of molecular fingerprint systems for drug molecules, including topological fingerprints, electro-topological state (E-state) fingerprints, MACCS keys, FP4 keys, atom pair fingerprints, topological torsion fingerprints, and Morgan/circular fingerprints. By combining different types of descriptors from drugs and proteins in different ways, interaction descriptors representing protein–protein or drug–protein interactions could be conveniently generated. These computed descriptors can be widely used in various fields relevant to chemoinformatics, bioinformatics, and chemogenomics. PyDPI is freely available via https://sourceforge.net/projects/pydpicao/

The predictive probability plot of screening all cross-linking drug-target pairs. The size of predictive probability gradually varies from green to red.

<p>The predictive probability plot of screening all cross-linking drug-target pairs. The size of predictive probability gradually varies from green to red.</p

Prediction results of five-fold cross validation using different models.

<p>TP: true positives; FN: false negatives; TN: true negatives; FP: false positives; Sen: sensitivity; Spe: specificity; Acc: accuracy.</p

ROCs and precision-recall curves with different K_i thresholds using RF.

<p>(A) ROCs (B) precision-recall curves. The auPRCs drop with the decreasing of K_i thresholds. However, the varying trend of auROCs is consistent with that of auPRCs.</p

ROCs and precision-recall curves for Naïve Bayes (green) and random forest (red) with full and selected features.

<p>(A) ROCs (B) precision-recall curves.</p

Outline of our methodology.

<p>(A) Interaction features are calculated by combing the fingerprint descriptors from drugs and the CTD and amino acid composition descriptors from protein sequences. These feature vectors are used to find the optimal RF parameters which most accurately separate the positive and negative training sets. The independent validation sets are used for further validation for the RF model. (B) Once the RF model is constructed, we can predict new unknown drug-target associations or screen all cross-linking associations.</p

Prediction statistics on different false discovery rates.

<p>FDR: false discovery rate, Number: Number of drug-target pairs predicted as interactions, Ratio: the ratio between drug target pairs predicted as interactions and all screening pairs on specific FDR.</p