Objective To discover candidate drugs to repurpose for COVID-19 using literature-derived knowledge and knowledge graph completion methods. Methods We propose a novel, integrative, and neural network-based literature-based discovery (LBD) approach to identify drug candidates from PubMed and other COVID-19-focused research literature. Our approach relies on semantic triples extracted using SemRep (via SemMedDB). We identified an informative and accurate subset of semantic triples using filtering rules and an accuracy classifier developed on a BERT variant. We used this subset to construct a knowledge graph, and applied five state-of-the-art, neural knowledge graph completion algorithms (TransE, RotatE, DistMult, ComplEx, and STELP) to predict drug repurposing candidates. The models were trained and assessed using a time slicing approach and the predicted drugs were compared with a list of drugs reported in the literature and evaluated in clinical trials. These models were complemented by a discovery pattern-based approach. Results Accuracy classifier based on PubMedBERT achieved the best performance (F 1 = 0.854) in classifying semantic predications. Among five knowledge graph completion models, TransE outperformed others (MR = 0.923, Hits@1 = 0.417). Some known drugs linked to COVID-19 in the literature were identified, as well as others that have not yet been studied. Discovery patterns enabled identification of additional candidate drugs and generation of plausible hypotheses regarding the links between the candidate drugs and COVID-19. Among them, five highly ranked and novel drugs (paclitaxel, SB 203580, alpha 2-antiplasmin, metoclopramide, and oxymatrine) and the mechanistic explanations for their potential use are further discussed. Conclusion We showed that a LBD approach can be feasible not only for discovering drug candidates for COVID-19, but also for generating mechanistic explanations. Our approach can be generalized to other diseases as well as to other clinical questions. Source code and data are available at https://github.com/kilicogluh/lbd-covid.

Objective The objective of this study is to develop a deep learning pipeline to detect signals on dietary supplement-related adverse events (DS AEs) from Twitter. Materials and Methods We obtained 247 807 tweets ranging from 2012 to 2018 that mentioned both DS and AE. We designed a tailor-made annotation guideline for DS AEs and annotated biomedical entities and relations on 2000 tweets. For the concept extraction task, we fine-tuned and compared the performance of BioClinical-BERT, PubMedBERT, ELECTRA, RoBERTa, and DeBERTa models with a CRF classifier. For the relation extraction task, we fine-tuned and compared BERT models to BioClinical-BERT, PubMedBERT, RoBERTa, and DeBERTa models. We chose the best-performing models in each task to assemble an end-to-end deep learning pipeline to detect DS AE signals and compared the results to the known DS AEs from a DS knowledge base (ie, iDISK). Results DeBERTa-CRF model outperformed other models in the concept extraction task, scoring a lenient microaveraged F1 score of 0.866. RoBERTa model outperformed other models in the relation extraction task, scoring a lenient microaveraged F1 score of 0.788. The end-to-end pipeline built on these 2 models was able to extract DS indication and DS AEs with a lenient microaveraged F1 score of 0.666. Conclusion We have developed a deep learning pipeline that can detect DS AE signals from Twitter. We have found DS AEs that were not recorded in an existing knowledge base (iDISK) and our proposed pipeline can as sist DS AE pharmacovigilance.

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Background Since no effective therapies exist for Alzheimer’s disease (AD), prevention has become more critical through lifestyle status changes and interventions. Analyzing electronic health records (EHRs) of patients with AD can help us better understand lifestyle’s effect on AD. However, lifestyle information is typically stored in clinical narratives. Thus, the objective of the study was to compare different natural language processing (NLP) models on classifying the lifestyle statuses (e.g., physical activity and excessive diet) from clinical texts in English. Methods Based on the collected concept unique identifiers (CUIs) associated with the lifestyle status, we extracted all related EHRs for patients with AD from the Clinical Data Repository (CDR) of the University of Minnesota (UMN). We automatically generated labels for the training data by using a rule-based NLP algorithm. We conducted weak supervision for pre-trained Bidirectional Encoder Representations from Transformers (BERT) models and three traditional machine learning models as baseline models on the weakly labeled training corpus. These models include the BERT base model, PubMedBERT (abstracts + full text), PubMedBERT (only abstracts), Unified Medical Language System (UMLS) BERT, Bio BERT, Bio-clinical BERT, logistic regression, support vector machine, and random forest. The rule-based model used for weak supervision was tested on the GSC for comparison. We performed two case studies: physical activity and excessive diet, in order to validate the effectiveness of BERT models in classifying lifestyle status for all models were evaluated and compared on the developed Gold Standard Corpus (GSC) on the two case studies. Results The UMLS BERT model achieved the best performance for classifying status of physical activity, with its precision, recall, and F-1 scores of 0.93, 0.93, and 0.92, respectively. Regarding classifying excessive diet, the Bio-clinical BERT model showed the best performance with precision, recall, and F-1 scores of 0.93, 0.93, and 0.93, respectively. Conclusion The proposed approach leveraging weak supervision could significantly increase the sample size, which is required for training the deep learning models. By comparing with the traditional machine learning models, the study also demonstrates the high performance of BERT models for classifying lifestyle status for Alzheimer’s disease in clinical notes.

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