Accelerating Complex Disease Treatment through Network Medicine and GenAI: A Case Study on Drug Repurposing for Breast Cancer

The objective of this research is to introduce a network specialized in predicting drugs that can be repurposed by investigating real-world evidence sources, such as clinical trials and biomedical literature. Specifically, it aims to generate drug combination therapies for complex diseases (e.g., cancer, Alzheimer's). We present a multilayered network medicine approach, empowered by a highly configured ChatGPT prompt engineering system, which is constructed on the fly to extract drug mentions in clinical trials. Additionally, we introduce a novel algorithm that connects real-world evidence with disease-specific signaling pathways (e.g., KEGG database). This sheds light on the repurposability of drugs if they are found to bind with one or more protein constituents of a signaling pathway. To demonstrate, we instantiated the framework for breast cancer and found that, out of 46 breast cancer signaling pathways, the framework identified 38 pathways that were covered by at least two drugs. This evidence signals the potential for combining those drugs. Specifically, the most covered signaling pathway, ID hsa:2064, was covered by 108 drugs, some of which can be combined. Conversely, the signaling pathway ID hsa:1499 was covered by only two drugs, indicating a significant gap for further research. Our network medicine framework, empowered by GenAI, shows promise in identifying drug combinations with a high degree of specificity, knowing the exact signaling pathways and proteins that serve as targets. It is noteworthy that ChatGPT successfully accelerated the process of identifying drug mentions in clinical trials, though further investigations are required to determine the relationships among the drug mentions.

Reinforcement of Explainability of ChatGPT Prompts by Embedding Breast Cancer Self-Screening Rules into AI Responses

Addressing the global challenge of breast cancer, this research explores the fusion of generative AI, focusing on ChatGPT 3.5 turbo model, and the intricacies of breast cancer risk assessment. The research aims to evaluate ChatGPT's reasoning capabilities, emphasizing its potential to process rules and provide explanations for screening recommendations. The study seeks to bridge the technology gap between intelligent machines and clinicians by demonstrating ChatGPT's unique proficiency in natural language reasoning. The methodology employs a supervised prompt-engineering approach to enforce detailed explanations for ChatGPT's recommendations. Synthetic use cases, generated algorithmically, serve as the testing ground for the encoded rules, evaluating the model's processing prowess. Findings highlight ChatGPT's promising capacity in processing rules comparable to Expert System Shells, with a focus on natural language reasoning. The research introduces the concept of reinforcement explainability, showcasing its potential in elucidating outcomes and facilitating user-friendly interfaces for breast cancer risk assessment.

Quantifying Similarity: Text-Mining Approaches to Evaluate ChatGPT and Google Bard Content in Relation to BioMedical Literature

Background: The emergence of generative AI tools, empowered by Large Language Models (LLMs), has shown powerful capabilities in generating content. To date, the assessment of the usefulness of such content, generated by what is known as prompt engineering, has become an interesting research question. Objectives Using the mean of prompt engineering, we assess the similarity and closeness of such contents to real literature produced by scientists. Methods In this exploratory analysis, (1) we prompt-engineer ChatGPT and Google Bard to generate clinical content to be compared with literature counterparts, (2) we assess the similarities of the contents generated by comparing them with counterparts from biomedical literature. Our approach is to use text-mining approaches to compare documents and associated bigrams and to use network analysis to assess the terms' centrality. Results The experiments demonstrated that ChatGPT outperformed Google Bard in cosine document similarity (38% to 34%), Jaccard document similarity (23% to 19%), TF-IDF bigram similarity (47% to 41%), and term network centrality (degree and closeness). We also found new links that emerged in ChatGPT bigram networks that did not exist in literature bigram networks. Conclusions: The obtained similarity results show that ChatGPT outperformed Google Bard in document similarity, bigrams, and degree and closeness centrality. We also observed that ChatGPT offers linkage to terms that are connected in the literature. Such connections could inspire asking interesting questions and generate new hypotheses.

Improving Detection of ChatGPT-Generated Fake Science Using Real Publication Text: Introducing xFakeBibs a Supervised-Learning Network Algorithm

ChatGPT is becoming a new reality. In this paper, we show how to distinguish ChatGPT-generated publications from counterparts produced by scientists. Using a newly designed supervised Machine Learning algorithm, we demonstrate how to detect machine-generated publications from those produced by scientists. The algorithm was trained using 100 real publication abstracts, followed by a 10-fold calibration approach to establish a lower-upper bound range of acceptance. In the comparison with ChatGPT content, it was evident that ChatGPT contributed merely 23\% of the bigram content, which is less than 50\% of any of the other 10 calibrating folds. This analysis highlights a significant disparity in technical terms where ChatGPT fell short of matching real science. When categorizing the individual articles, the xFakeBibs algorithm accurately identified 98 out of 100 publications as fake, with 2 articles incorrectly classified as real publications. Though this work introduced an algorithmic approach that detected the ChatGPT-generated fake science with a high degree of accuracy, it remains challenging to detect all fake records. This work is indeed a step in the right direction to counter fake science and misinformation.

Establishing Trust in ChatGPT BioMedical Generated Text: An Ontology-Based Knowledge Graph to Validate Disease-Symptom Links

Methods: Through an innovative approach, we construct ontology-based knowledge graphs from authentic medical literature and AI-generated content. Our goal is to distinguish factual information from unverified data. We compiled two datasets: one from biomedical literature using a "human disease and symptoms" query, and another generated by ChatGPT, simulating articles. With these datasets (PubMed and ChatGPT), we curated 10 sets of 250 abstracts each, selected randomly with a specific seed. Our method focuses on utilizing disease ontology (DOID) and symptom ontology (SYMP) to build knowledge graphs, robust mathematical models that facilitate unbiased comparisons. By employing our fact-checking algorithms and network centrality metrics, we conducted GPT disease-symptoms link analysis to quantify the accuracy of factual knowledge amid noise, hypotheses, and significant findings. Results: The findings obtained from the comparison of diverse ChatGPT knowledge graphs with their PubMed counterparts revealed some interesting observations. While PubMed knowledge graphs exhibit a wealth of disease-symptom terms, it is surprising to observe that some ChatGPT graphs surpass them in the number of connections. Furthermore, some GPT graphs are demonstrating supremacy of the centrality scores, especially for the overlapping nodes. This striking contrast indicates the untapped potential of knowledge that can be derived from AI-generated content, awaiting verification. Out of all the graphs, the factual link ratio between any two graphs reached its peak at 60%. Conclusions: An intriguing insight from our findings was the striking number of links among terms in the knowledge graph generated from ChatGPT datasets, surpassing some of those in its PubMed counterpart. This early discovery has prompted further investigation using universal network metrics to unveil the new knowledge the links may hold.