Can machine learning 'transform' peptides/peptidomimetics into small molecules? A case study with ghrelin receptor ligands.

There has been considerable interest in transforming peptides into small molecules as peptide-based molecules often present poorer bioavailability and lower metabolic stability. Our studies looked into building machine learning (ML) models to investigate if ML is able to identify the 'bioactive' features of peptides and use the features to accurately discriminate between binding and non-binding small molecules. The ghrelin receptor (GR), a receptor that is implicated in various diseases, was used as an example to demonstrate whether ML models derived from a peptide library can be used to predict small molecule binders. ML models based on three different algorithms, namely random forest, support vector machine, and extreme gradient boosting, were built based on a carefully curated dataset of peptide/peptidomimetic and small molecule GR ligands. The results indicated that ML models trained with a dataset exclusively composed of peptides/peptidomimetics provide limited predictive power for small molecules, but that ML models trained with a diverse dataset composed of an array of both peptides/peptidomimetics and small molecules displayed exceptional results in terms of accuracy and false rates. The diversified models can accurately differentiate the binding small molecules from non-binding small molecules using an external validation set with new small molecules that we synthesized previously. Structural features that are the most critical contributors to binding activity were extracted and are remarkably consistent with the crystallography and mutagenesis studies.

Utilizing deep learning and graph mining to identify drug use on Twitter data.

BACKGROUND: The collection and examination of social media has become a useful mechanism for studying the mental activity and behavior tendencies of users. Through the analysis of a collected set of Twitter data, a model will be developed for predicting positively referenced, drug-related tweets. From this, trends and correlations can be determined. METHODS: Social media data (tweets and attributes) were collected and processed using topic pertaining keywords, such as drug slang and use-conditions (methods of drug consumption). Potential candidates were preprocessed resulting in a dataset of 3,696,150 rows. The predictive classification power of multiple methods was compared including SVM, XGBoost, BERT and CNN-based classifiers. For the latter, a deep learning approach was implemented to screen and analyze the semantic meaning of the tweets. RESULTS: To test the predictive capability of the model, SVM and XGBoost were first employed. The results calculated from the models respectively displayed an accuracy of 59.33% and 54.90%, with AUC's of 0.87 and 0.71. The values show a low predictive capability with little discrimination. Conversely, the CNN-based classifiers presented a significant improvement, between the two models tested. The first was trained with 2661 manually labeled samples, while the other included synthetically generated tweets culminating in 12,142 samples. The accuracy scores were 76.35% and 82.31%, with an AUC of 0.90 and 0.91. Using association rule mining in conjunction with the CNN-based classifier showed a high likelihood for keywords such as "smoke", "cocaine", and "marijuana" triggering a drug-positive classification. CONCLUSION: Predictive analysis with a CNN is promising, whereas attribute-based models presented little predictive capability and were not suitable for analyzing text of data. This research found that the commonly mentioned drugs had a level of correspondence with frequently used illicit substances, proving the practical usefulness of this system. Lastly, the synthetically generated set provided increased accuracy scores and improves the predictive capability.