Combinatorial Design of Molecule using Activity-Linked Substructural Topological Information as Applied to Antitubercular Compounds

Background: Generating a large number of compounds using combinatorial methods increases the possibility of finding novel bioactive compounds. Although some combinatorial structure generation algorithms are available, any method for generating structures from activity-linked substructural topological information is not yet reported. Objective: To develop a method using graph-theoretical techniques for generating structures of antitubercular compounds combinatorially from activity-linked substructural topological information, predict activity and prioritize and screen potential drug candidates. Methods: Activity related vertices are identified from datasets composed of both active and inactive or, differently active compounds and structures are generated combinatorially using the topological distance distribution associated with those vertices. Biological activities are predicted using topological distance based vertex indices and a rule based method. Generated structures are prioritized using a newly defined Molecular Priority Score (MPS). Results: Studies considering a series of Acid Alkyl Ester (AAE) compounds and three known antitubercular drugs show that active compounds can be generated from substructural information of other active compounds for all these classes of compounds. Activity predictions show high level of success rate and a number of highly active AAE compounds produced high MPS score indicating that MPS score may help prioritize and screen potential drug molecules. A possible relation of this work with scaffold hopping and inverse Quantitative Structure-Activity Relationship (iQSAR) problem has also been discussed. Conclusion: The proposed method seems to hold promise for discovering novel therapeutic candidates for combating Tuberculosis and may be useful for discovering novel drug molecules for the treatment of other diseases as well

Extraction of Explicit and Implicit Cause-Effect Relationships in Patient-Reported Diabetes-Related Tweets From 2017 to 2021: Deep Learning Approach

Background Intervening in and preventing diabetes distress requires an understanding of its causes and, in particular, from a patient’s perspective. Social media data provide direct access to how patients see and understand their disease and consequently show the causes of diabetes distress. Objective Leveraging machine learning methods, we aim to extract both explicit and implicit cause-effect relationships in patient-reported diabetes-related tweets and provide a methodology to better understand the opinions, feelings, and observations shared within the diabetes online community from a causality perspective. Methods More than 30 million diabetes-related tweets in English were collected between April 2017 and January 2021. Deep learning and natural language processing methods were applied to focus on tweets with personal and emotional content. A cause-effect tweet data set was manually labeled and used to train (1) a fine-tuned BERTweet model to detect causal sentences containing a causal relation and (2) a conditional random field model with Bidirectional Encoder Representations from Transformers (BERT)-based features to extract possible cause-effect associations. Causes and effects were clustered in a semisupervised approach and visualized in an interactive cause-effect network. Results Causal sentences were detected with a recall of 68% in an imbalanced data set. A conditional random field model with BERT-based features outperformed a fine-tuned BERT model for cause-effect detection with a macro recall of 68%. This led to 96,676 sentences with cause-effect relationships. “Diabetes” was identified as the central cluster followed by “death” and “insulin.” Insulin pricing–related causes were frequently associated with death. Conclusions A novel methodology was developed to detect causal sentences and identify both explicit and implicit, single and multiword cause, and the corresponding effect, as expressed in diabetes-related tweets leveraging BERT-based architectures and visualized as cause-effect network. Extracting causal associations in real life, patient-reported outcomes in social media data provide a useful complementary source of information in diabetes research