Funding and support: The Generative AI Challenge is funded by grants from the Future Health Research and Innovation Fund (FHRIF), Grant ID IC2023-GAIA/11. Conflict of interest statement: The authors declare no conflicts of interest. Abstract This exploratory pilot study investigated the potential of combining a domain-specific model, BERN2, with large language models (LLMs) to enhance automated disease phenotyping from research survey data. Motivated by the need for efficient and accurate methods to harmonize the growing volume of survey data with standardized disease ontologies, we employed BERN2, a biomedical named entity recognition and normalization model, to extract disease information from the ORIGINS birth cohort survey data. After rigorously evaluating BERN2's performance against a manually curated ground truth dataset, we integrated various LLMs using prompt engineering, Retrieval-Augmented Generation (RAG), and Instructional Fine-Tuning (IFT) to refine the model's outputs. BERN2 demonstrated high performance in extracting and normalizing disease mentions, and the integration of LLMs, particularly with Few Shot Inference and RAG orchestration, further improved accuracy. This approach, especially when incorporating structured examples, logical reasoning prompts, and detailed context, offers a promising avenue for developing tools to enable efficient cohort profiling and data harmonization across large, heterogeneous research datasets. Introduction The increasing availability of research survey data from cohort studies and clinical trials offers unprecedented opportunities to advance biomedical research and improve healthcare (1).

While machine learning (ML) includes a valuable array of tools for analyzing biomedical data, significant time and expertise is required to assemble effective, rigorous, and unbiased pipelines. Automated ML (AutoML) tools seek to facilitate ML application by automating a subset of analysis pipeline elements. In this study we develop and validate a Simple, Transparent, End-to-end Automated Machine Learning Pipeline (STREAMLINE) and apply it to investigate the added utility of photography-based phenotypes for predicting obstructive sleep apnea (OSA); a common and underdiagnosed condition associated with a variety of health, economic, and safety consequences. STREAMLINE is designed to tackle biomedical binary classification tasks while adhering to best practices and accommodating complexity, scalability, reproducibility, customization, and model interpretation. Benchmarking analyses validated the efficacy of STREAMLINE across data simulations with increasingly complex patterns of association. Then we applied STREAMLINE to evaluate the utility of demographics (DEM), self-reported comorbidities (DX), symptoms (SYM), and photography-based craniofacial (CF) and intraoral (IO) anatomy measures in predicting any OSA or moderate/severe OSA using 3,111 participants from Sleep Apnea Global Interdisciplinary Consortium (SAGIC). OSA analyses identified a significant increase in ROC-AUC when adding CF to DEM+DX+SYM to predict moderate/severe OSA. A consistent but non-significant increase in PRC-AUC was observed with the addition of each subsequent feature set to predict any OSA, with CF and IO yielding minimal improvements. Application of STREAMLINE to OSA data suggests that CF features provide additional value in predicting moderate/severe OSA, but neither CF nor IO features meaningfully improved the prediction of any OSA beyond established demographics, comorbidity and symptom characteristics.

Objective: Clinical deep phenotyping and phenotype annotation play a critical role in both the diagnosis of patients with rare disorders as well as in building computationally-tractable knowledge in the rare disorders field. These processes rely on using ontology concepts, often from the Human Phenotype Ontology, in conjunction with a phenotype concept recognition task (supported usually by machine learning methods) to curate patient profiles or existing scientific literature. With the significant shift in the use of large language models (LLMs) for most NLP tasks, we examine the performance of the latest Generative Pre-trained Transformer (GPT) models underpinning ChatGPT as a foundation for the tasks of clinical phenotyping and phenotype annotation. Materials and Methods: The experimental setup of the study included seven prompts of various levels of specificity, two GPT models (gpt-3.5-turbo and gpt-4.0) and two established gold standard corpora for phenotype recognition, one consisting of publication abstracts and the other clinical observations. Results: Our results show that, with an appropriate setup, these models can achieve state of the art performance. The best run, using few-shot learning, achieved 0.58 macro F1 score on publication abstracts and 0.75 macro F1 score on clinical observations, the former being comparable with the state of the art, while the latter surpassing the current best in class tool. Conclusion: While the results are promising, the non-deterministic nature of the outcomes, the high cost and the lack of concordance between different runs using the same prompt and input make the use of these LLMs challenging for this particular task.