Abstract:Objectives: The vast and complex nature of human genomic sequencing data presents challenges for effective analysis. This review aims to investigate the application of Natural Language Processing (NLP) techniques, particularly Large Language Models (LLMs) and transformer architectures, in deciphering genomic codes, focusing on tokenization, transformer models, and regulatory annotation prediction. The goal of this review is to assess data and model accessibility in the most recent literature, gaining a better understanding of the existing capabilities and constraints of these tools in processing genomic sequencing data. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, our scoping review was conducted across PubMed, Medline, Scopus, Web of Science, Embase, and ACM Digital Library. Studies were included if they focused on NLP methodologies applied to genomic sequencing data analysis, without restrictions on publication date or article type. Results: A total of 26 studies published between 2021 and April 2024 were selected for review. The review highlights that tokenization and transformer models enhance the processing and understanding of genomic data, with applications in predicting regulatory annotations like transcription-factor binding sites and chromatin accessibility. Discussion: The application of NLP and LLMs to genomic sequencing data interpretation is a promising field that can help streamline the processing of large-scale genomic data while also providing a better understanding of its complex structures. It has the potential to drive advancements in personalized medicine by offering more efficient and scalable solutions for genomic analysis. Further research is also needed to discuss and overcome current limitations, enhancing model transparency and applicability.
Abstract:Despite significant progress in applying large language models (LLMs) to the medical domain, several limitations still prevent them from practical applications. Among these are the constraints on model size and the lack of cohort-specific labeled datasets. In this work, we investigated the potential of improving a lightweight LLM, such as Llama 3.1-8B, through fine-tuning with datasets using synthetic labels. Two tasks are jointly trained by combining their respective instruction datasets. When the quality of the task-specific synthetic labels is relatively high (e.g., generated by GPT4- o), Llama 3.1-8B achieves satisfactory performance on the open-ended disease detection task, with a micro F1 score of 0.91. Conversely, when the quality of the task-relevant synthetic labels is relatively low (e.g., from the MIMIC-CXR dataset), fine-tuned Llama 3.1-8B is able to surpass its noisy teacher labels (micro F1 score of 0.67 v.s. 0.63) when calibrated against curated labels, indicating the strong inherent underlying capability of the model. These findings demonstrate the potential of fine-tuning LLMs with synthetic labels, offering a promising direction for future research on LLM specialization in the medical domain.
Abstract:Large language models (LLMs) hold great promise in summarizing medical evidence. Most recent studies focus on the application of proprietary LLMs. Using proprietary LLMs introduces multiple risk factors, including a lack of transparency and vendor dependency. While open-source LLMs allow better transparency and customization, their performance falls short compared to proprietary ones. In this study, we investigated to what extent fine-tuning open-source LLMs can further improve their performance in summarizing medical evidence. Utilizing a benchmark dataset, MedReview, consisting of 8,161 pairs of systematic reviews and summaries, we fine-tuned three broadly-used, open-sourced LLMs, namely PRIMERA, LongT5, and Llama-2. Overall, the fine-tuned LLMs obtained an increase of 9.89 in ROUGE-L (95% confidence interval: 8.94-10.81), 13.21 in METEOR score (95% confidence interval: 12.05-14.37), and 15.82 in CHRF score (95% confidence interval: 13.89-16.44). The performance of fine-tuned LongT5 is close to GPT-3.5 with zero-shot settings. Furthermore, smaller fine-tuned models sometimes even demonstrated superior performance compared to larger zero-shot models. The above trends of improvement were also manifested in both human and GPT4-simulated evaluations. Our results can be applied to guide model selection for tasks demanding particular domain knowledge, such as medical evidence summarization.
Abstract:The study examines the application of GPT-4V, a multi-modal large language model equipped with visual recognition, in detecting radiological findings from a set of 100 chest radiographs and suggests that GPT-4V is currently not ready for real-world diagnostic usage in interpreting chest radiographs.
Abstract:Data accuracy is essential for scientific research and policy development. The National Violent Death Reporting System (NVDRS) data is widely used for discovering the patterns and causes of death. Recent studies suggested the annotation inconsistencies within the NVDRS and the potential impact on erroneous suicide-cause attributions. We present an empirical Natural Language Processing (NLP) approach to detect annotation inconsistencies and adopt a cross-validation-like paradigm to identify problematic instances. We analyzed 267,804 suicide death incidents between 2003 and 2020 from the NVDRS. Our results showed that incorporating the target state's data into training the suicide-crisis classifier brought an increase of 5.4% to the F-1 score on the target state's test set and a decrease of 1.1% on other states' test set. To conclude, we demonstrated the annotation inconsistencies in NVDRS's death investigation notes, identified problematic instances, evaluated the effectiveness of correcting problematic instances, and eventually proposed an NLP improvement solution.
Abstract:Recent studies indicate that Generative Pre-trained Transformer 4 with Vision (GPT-4V) outperforms human physicians in medical challenge tasks. However, these evaluations primarily focused on the accuracy of multi-choice questions alone. Our study extends the current scope by conducting a comprehensive analysis of GPT-4V's rationales of image comprehension, recall of medical knowledge, and step-by-step multimodal reasoning when solving New England Journal of Medicine (NEJM) Image Challenges - an imaging quiz designed to test the knowledge and diagnostic capabilities of medical professionals. Evaluation results confirmed that GPT-4V outperforms human physicians regarding multi-choice accuracy (88.0% vs. 77.0%, p=0.034). GPT-4V also performs well in cases where physicians incorrectly answer, with over 80% accuracy. However, we discovered that GPT-4V frequently presents flawed rationales in cases where it makes the correct final choices (27.3%), most prominent in image comprehension (21.6%). Regardless of GPT-4V's high accuracy in multi-choice questions, our findings emphasize the necessity for further in-depth evaluations of its rationales before integrating such models into clinical workflows.
Abstract:Objectives Extraction of PICO (Populations, Interventions, Comparison, and Outcomes) entities is fundamental to evidence retrieval. We present a novel method PICOX to extract overlapping PICO entities. Materials and Methods PICOX first identifies entities by assessing whether a word marks the beginning or conclusion of an entity. Then it uses a multi-label classifier to assign one or more PICO labels to a span candidate. PICOX was evaluated using one of the best-performing baselines, EBM-NLP, and three more datasets, i.e., PICO-Corpus, and RCT publications on Alzheimer's Disease or COVID-19, using entity-level precision, recall, and F1 scores. Results PICOX achieved superior precision, recall, and F1 scores across the board, with the micro F1 score improving from 45.05 to 50.87 (p << 0.01). On the PICO-Corpus, PICOX obtained higher recall and F1 scores than the baseline and improved the micro recall score from 56.66 to 67.33. On the COVID-19 dataset, PICOX also outperformed the baseline and improved the micro F1 score from 77.10 to 80.32. On the AD dataset, PICOX demonstrated comparable F1 scores with higher precision when compared to the baseline. Conclusion PICOX excels in identifying overlapping entities and consistently surpasses a leading baseline across multiple datasets. Ablation studies reveal that its data augmentation strategy effectively minimizes false positives and improves precision.
Abstract:Many real-world image recognition problems, such as diagnostic medical imaging exams, are "long-tailed" $\unicode{x2013}$ there are a few common findings followed by many more relatively rare conditions. In chest radiography, diagnosis is both a long-tailed and multi-label problem, as patients often present with multiple findings simultaneously. While researchers have begun to study the problem of long-tailed learning in medical image recognition, few have studied the interaction of label imbalance and label co-occurrence posed by long-tailed, multi-label disease classification. To engage with the research community on this emerging topic, we conducted an open challenge, CXR-LT, on long-tailed, multi-label thorax disease classification from chest X-rays (CXRs). We publicly release a large-scale benchmark dataset of over 350,000 CXRs, each labeled with at least one of 26 clinical findings following a long-tailed distribution. We synthesize common themes of top-performing solutions, providing practical recommendations for long-tailed, multi-label medical image classification. Finally, we use these insights to propose a path forward involving vision-language foundation models for few- and zero-shot disease classification.