Qingyu Chen

Qingyu Chen, Jingcheng Du, Alexis Allot et al.

The rapid growth of biomedical literature poses a significant challenge for curation and interpretation. This has become more evident during the COVID-19 pandemic. LitCovid, a literature database of COVID-19 related papers in PubMed, has accumulated over 180,000 articles with millions of accesses. Approximately 10,000 new articles are added to LitCovid every month. A main curation task in LitCovid is topic annotation where an article is assigned with up to eight topics, e.g., Treatment and Diagnosis. The annotated topics have been widely used both in LitCovid (e.g., accounting for ~18% of total uses) and downstream studies such as network generation. However, it has been a primary curation bottleneck due to the nature of the task and the rapid literature growth. This study proposes LITMC-BERT, a transformer-based multi-label classification method in biomedical literature. It uses a shared transformer backbone for all the labels while also captures label-specific features and the correlations between label pairs. We compare LITMC-BERT with three baseline models on two datasets. Its micro-F1 and instance-based F1 are 5% and 4% higher than the current best results, respectively, and only requires ~18% of the inference time than the Binary BERT baseline. The related datasets and models are available via https://github.com/ncbi/ml-transformer.

Shubo Tian, Qiao Jin, Lana Yeganova et al. · tsinghua

ChatGPT has drawn considerable attention from both the general public and domain experts with its remarkable text generation capabilities. This has subsequently led to the emergence of diverse applications in the field of biomedicine and health. In this work, we examine the diverse applications of large language models (LLMs), such as ChatGPT, in biomedicine and health. Specifically we explore the areas of biomedical information retrieval, question answering, medical text summarization, information extraction, and medical education, and investigate whether LLMs possess the transformative power to revolutionize these tasks or whether the distinct complexities of biomedical domain presents unique challenges. Following an extensive literature survey, we find that significant advances have been made in the field of text generation tasks, surpassing the previous state-of-the-art methods. For other applications, the advances have been modest. Overall, LLMs have not yet revolutionized biomedicine, but recent rapid progress indicates that such methods hold great potential to provide valuable means for accelerating discovery and improving health. We also find that the use of LLMs, like ChatGPT, in the fields of biomedicine and health entails various risks and challenges, including fabricated information in its generated responses, as well as legal and privacy concerns associated with sensitive patient data. We believe this survey can provide a comprehensive and timely overview to biomedical researchers and healthcare practitioners on the opportunities and challenges associated with using ChatGPT and other LLMs for transforming biomedicine and health.

Ling Luo, Chih-Hsuan Wei, Po-Ting Lai et al.

The automatic assignment of species information to the corresponding genes in a research article is a critically important step in the gene normalization task, whereby a gene mention is normalized and linked to a database record or identifier by a text-mining algorithm. Existing methods typically rely on heuristic rules based on gene and species co-occurrence in the article, but their accuracy is suboptimal. We therefore developed a high-performance method, using a novel deep learning-based framework, to classify whether there is a relation between a gene and a species. Instead of the traditional binary classification framework in which all possible pairs of genes and species in the same article are evaluated, we treat the problem as a sequence-labeling task such that only a fraction of the pairs needs to be considered. Our benchmarking results show that our approach obtains significantly higher performance compared to that of the rule-based baseline method for the species assignment task (from 65.8% to 81.3% in accuracy). The source code and data for species assignment are freely available at https://github.com/ncbi/SpeciesAssignment.

Li Fang, Qingyu Chen, Chih-Hsuan Wei et al.

Pretrained language models such as Bidirectional Encoder Representations from Transformers (BERT) have achieved state-of-the-art performance in natural language processing (NLP) tasks. Recently, BERT has been adapted to the biomedical domain. Despite the effectiveness, these models have hundreds of millions of parameters and are computationally expensive when applied to large-scale NLP applications. We hypothesized that the number of parameters of the original BERT can be dramatically reduced with minor impact on performance. In this study, we present Bioformer, a compact BERT model for biomedical text mining. We pretrained two Bioformer models (named Bioformer8L and Bioformer16L) which reduced the model size by 60% compared to BERTBase. Bioformer uses a biomedical vocabulary and was pre-trained from scratch on PubMed abstracts and PubMed Central full-text articles. We thoroughly evaluated the performance of Bioformer as well as existing biomedical BERT models including BioBERT and PubMedBERT on 15 benchmark datasets of four different biomedical NLP tasks: named entity recognition, relation extraction, question answering and document classification. The results show that with 60% fewer parameters, Bioformer16L is only 0.1% less accurate than PubMedBERT while Bioformer8L is 0.9% less accurate than PubMedBERT. Both Bioformer16L and Bioformer8L outperformed BioBERTBase-v1.1. In addition, Bioformer16L and Bioformer8L are 2-3 fold as fast as PubMedBERT/BioBERTBase-v1.1. Bioformer has been successfully deployed to PubTator Central providing gene annotations over 35 million PubMed abstracts and 5 million PubMed Central full-text articles. We make Bioformer publicly available via https://github.com/WGLab/bioformer, including pre-trained models, datasets, and instructions for downstream use.

Qiao Jin, Yifan Yang, Qingyu Chen et al. · tsinghua

While large language models (LLMs) have been successfully applied to various tasks, they still face challenges with hallucinations. Augmenting LLMs with domain-specific tools such as database utilities can facilitate easier and more precise access to specialized knowledge. In this paper, we present GeneGPT, a novel method for teaching LLMs to use the Web APIs of the National Center for Biotechnology Information (NCBI) for answering genomics questions. Specifically, we prompt Codex to solve the GeneTuring tests with NCBI Web APIs by in-context learning and an augmented decoding algorithm that can detect and execute API calls. Experimental results show that GeneGPT achieves state-of-the-art performance on eight tasks in the GeneTuring benchmark with an average score of 0.83, largely surpassing retrieval-augmented LLMs such as the new Bing (0.44), biomedical LLMs such as BioMedLM (0.08) and BioGPT (0.04), as well as GPT-3 (0.16) and ChatGPT (0.12). Our further analyses suggest that: (1) API demonstrations have good cross-task generalizability and are more useful than documentations for in-context learning; (2) GeneGPT can generalize to longer chains of API calls and answer multi-hop questions in GeneHop, a novel dataset introduced in this work; (3) Different types of errors are enriched in different tasks, providing valuable insights for future improvements.

Qiao Jin, Won Kim, Qingyu Chen et al. · tsinghua

Information retrieval (IR) is essential in biomedical knowledge acquisition and clinical decision support. While recent progress has shown that language model encoders perform better semantic retrieval, training such models requires abundant query-article annotations that are difficult to obtain in biomedicine. As a result, most biomedical IR systems only conduct lexical matching. In response, we introduce MedCPT, a first-of-its-kind Contrastively Pre-trained Transformer model for zero-shot semantic IR in biomedicine. To train MedCPT, we collected an unprecedented scale of 255 million user click logs from PubMed. With such data, we use contrastive learning to train a pair of closely-integrated retriever and re-ranker. Experimental results show that MedCPT sets new state-of-the-art performance on six biomedical IR tasks, outperforming various baselines including much larger models such as GPT-3-sized cpt-text-XL. In addition, MedCPT also generates better biomedical article and sentence representations for semantic evaluations. As such, MedCPT can be readily applied to various real-world biomedical IR tasks.

Po-Ting Lai, Chih-Hsuan Wei, Ling Luo et al.

Biomedical relation extraction (RE) is the task of automatically identifying and characterizing relations between biomedical concepts from free text. RE is a central task in biomedical natural language processing (NLP) research and plays a critical role in many downstream applications, such as literature-based discovery and knowledge graph construction. State-of-the-art methods were used primarily to train machine learning models on individual RE datasets, such as protein-protein interaction and chemical-induced disease relation. Manual dataset annotation, however, is highly expensive and time-consuming, as it requires domain knowledge. Existing RE datasets are usually domain-specific or small, which limits the development of generalized and high-performing RE models. In this work, we present a novel framework for systematically addressing the data heterogeneity of individual datasets and combining them into a large dataset. Based on the framework and dataset, we report on BioREx, a data-centric approach for extracting relations. Our evaluation shows that BioREx achieves significantly higher performance than the benchmark system trained on the individual dataset, setting a new SOTA from 74.4% to 79.6% in F-1 measure on the recently released BioRED corpus. We further demonstrate that the combined dataset can improve performance for five different RE tasks. In addition, we show that on average BioREx compares favorably to current best-performing methods such as transfer learning and multi-task learning. Finally, we demonstrate BioREx's robustness and generalizability in two independent RE tasks not previously seen in training data: drug-drug N-ary combination and document-level gene-disease RE. The integrated dataset and optimized method have been packaged as a stand-alone tool available at https://github.com/ncbi/BioREx.

Rui Yang, Qingcheng Zeng, Keen You et al.

This study introduces Ascle, a pioneering natural language processing (NLP) toolkit designed for medical text generation. Ascle is tailored for biomedical researchers and healthcare professionals with an easy-to-use, all-in-one solution that requires minimal programming expertise. For the first time, Ascle evaluates and provides interfaces for the latest pre-trained language models, encompassing four advanced and challenging generative functions: question-answering, text summarization, text simplification, and machine translation. In addition, Ascle integrates 12 essential NLP functions, along with query and search capabilities for clinical databases. The toolkit, its models, and associated data are publicly available via https://github.com/Yale-LILY/MedGen.

Ling Luo, Chih-Hsuan Wei, Po-Ting Lai et al.

Biomedical named entity recognition (BioNER) seeks to automatically recognize biomedical entities in natural language text, serving as a necessary foundation for downstream text mining tasks and applications such as information extraction and question answering. Manually labeling training data for the BioNER task is costly, however, due to the significant domain expertise required for accurate annotation. The resulting data scarcity causes current BioNER approaches to be prone to overfitting, to suffer from limited generalizability, and to address a single entity type at a time (e.g., gene or disease). We therefore propose a novel all-in-one (AIO) scheme that uses external data from existing annotated resources to enhance the accuracy and stability of BioNER models. We further present AIONER, a general-purpose BioNER tool based on cutting-edge deep learning and our AIO schema. We evaluate AIONER on 14 BioNER benchmark tasks and show that AIONER is effective, robust, and compares favorably to other state-of-the-art approaches such as multi-task learning. We further demonstrate the practical utility of AIONER in three independent tasks to recognize entity types not previously seen in training data, as well as the advantages of AIONER over existing methods for processing biomedical text at a large scale (e.g., the entire PubMed data).

Robert Leaman, Rezarta Islamaj, Alexis Allot et al.

A significant percentage of COVID-19 survivors experience ongoing multisystemic symptoms that often affect daily living, a condition known as Long Covid or post-acute-sequelae of SARS-CoV-2 infection. However, identifying scientific articles relevant to Long Covid is challenging since there is no standardized or consensus terminology. We developed an iterative human-in-the-loop machine learning framework combining data programming with active learning into a robust ensemble model, demonstrating higher specificity and considerably higher sensitivity than other methods. Analysis of the Long Covid collection shows that (1) most Long Covid articles do not refer to Long Covid by any name (2) when the condition is named, the name used most frequently in the literature is Long Covid, and (3) Long Covid is associated with disorders in a wide variety of body systems. The Long Covid collection is updated weekly and is searchable online at the LitCovid portal: https://www.ncbi.nlm.nih.gov/research/coronavirus/docsum?filters=e_condition.LongCovid

Qingyu Chen, Alexis Allot, Robert Leaman et al.

The COVID-19 pandemic has been severely impacting global society since December 2019. Massive research has been undertaken to understand the characteristics of the virus and design vaccines and drugs. The related findings have been reported in biomedical literature at a rate of about 10,000 articles on COVID-19 per month. Such rapid growth significantly challenges manual curation and interpretation. For instance, LitCovid is a literature database of COVID-19-related articles in PubMed, which has accumulated more than 200,000 articles with millions of accesses each month by users worldwide. One primary curation task is to assign up to eight topics (e.g., Diagnosis and Treatment) to the articles in LitCovid. Despite the continuing advances in biomedical text mining methods, few have been dedicated to topic annotations in COVID-19 literature. To close the gap, we organized the BioCreative LitCovid track to call for a community effort to tackle automated topic annotation for COVID-19 literature. The BioCreative LitCovid dataset, consisting of over 30,000 articles with manually reviewed topics, was created for training and testing. It is one of the largest multilabel classification datasets in biomedical scientific literature. 19 teams worldwide participated and made 80 submissions in total. Most teams used hybrid systems based on transformers. The highest performing submissions achieved 0.8875, 0.9181, and 0.9394 for macro F1-score, micro F1-score, and instance-based F1-score, respectively. The level of participation and results demonstrate a successful track and help close the gap between dataset curation and method development. The dataset is publicly available via https://ftp.ncbi.nlm.nih.gov/pub/lu/LitCovid/biocreative/ for benchmarking and further development.

Qingyu Chen, Tiarnan D L Keenan, Elvira Agron et al.

Timely disease diagnosis is challenging due to increasing disease burdens and limited clinician availability. AI shows promise in diagnosis accuracy but faces real-world application issues due to insufficient validation in clinical workflows and diverse populations. This study addresses gaps in medical AI downstream accountability through a case study on age-related macular degeneration (AMD) diagnosis and severity classification. We designed and implemented an AI-assisted diagnostic workflow for AMD, comparing diagnostic performance with and without AI assistance among 24 clinicians from 12 institutions with real patient data sampled from the Age-Related Eye Disease Study (AREDS). Additionally, we demonstrated continual enhancement of an existing AI model by incorporating approximately 40,000 additional medical images (named AREDS2 dataset). The improved model was then systematically evaluated using both AREDS and AREDS2 test sets, as well as an external test set from Singapore. AI assistance markedly enhanced diagnostic accuracy and classification for 23 out of 24 clinicians, with the average F1-score increasing by 20% from 37.71 (Manual) to 45.52 (Manual + AI) (P-value < 0.0001), achieving an improvement of over 50% in some cases. In terms of efficiency, AI assistance reduced diagnostic times for 17 out of the 19 clinicians tracked, with time savings of up to 40%. Furthermore, a model equipped with continual learning showed robust performance across three independent datasets, recording a 29% increase in accuracy, and elevating the F1-score from 42 to 54 in the Singapore population.

Xinyue Hu, Lin Gu, Kazuma Kobayashi et al.

Medical visual question answering (VQA) aims to answer clinically relevant questions regarding input medical images. This technique has the potential to improve the efficiency of medical professionals while relieving the burden on the public health system, particularly in resource-poor countries. Existing medical VQA methods tend to encode medical images and learn the correspondence between visual features and questions without exploiting the spatial, semantic, or medical knowledge behind them. This is partially because of the small size of the current medical VQA dataset, which often includes simple questions. Therefore, we first collected a comprehensive and large-scale medical VQA dataset, focusing on chest X-ray images. The questions involved detailed relationships, such as disease names, locations, levels, and types in our dataset. Based on this dataset, we also propose a novel baseline method by constructing three different relationship graphs: spatial relationship, semantic relationship, and implicit relationship graphs on the image regions, questions, and semantic labels. The answer and graph reasoning paths are learned for different questions.

Rui Yang, Edison Marrese-Taylor, Yuhe Ke et al.

Large language models (LLMs) have demonstrated powerful text generation capabilities, bringing unprecedented innovation to the healthcare field. While LLMs hold immense promise for applications in healthcare, applying them to real clinical scenarios presents significant challenges, as these models may generate content that deviates from established medical facts and even exhibit potential biases. In our research, we develop an augmented LLM framework based on the Unified Medical Language System (UMLS), aiming to better serve the healthcare community. We employ LLaMa2-13b-chat and ChatGPT-3.5 as our benchmark models, and conduct automatic evaluations using the ROUGE Score and BERTScore on 104 questions from the LiveQA test set. Additionally, we establish criteria for physician-evaluation based on four dimensions: Factuality, Completeness, Readability and Relevancy. ChatGPT-3.5 is used for physician evaluation with 20 questions on the LiveQA test set. Multiple resident physicians conducted blind reviews to evaluate the generated content, and the results indicate that this framework effectively enhances the factuality, completeness, and relevance of generated content. Our research demonstrates the effectiveness of using UMLS-augmented LLMs and highlights the potential application value of LLMs in in medical question-answering.

Anran Li, Yuanyuan Chen, Chao Ren et al.

For privacy-preserving graph learning tasks involving distributed graph datasets, federated learning (FL)-based GCN (FedGCN) training is required. A key challenge for FedGCN is scaling to large-scale graphs, which typically incurs high computation and communication costs when dealing with the explosively increasing number of neighbors. Existing graph sampling-enhanced FedGCN training approaches ignore graph structural information or dynamics of optimization, resulting in high variance and inaccurate node embeddings. To address this limitation, we propose the Federated Adaptive Importance-based Sampling (FedAIS) approach. It achieves substantial computational cost saving by focusing the limited resources on training important nodes, while reducing communication overhead via adaptive historical embedding synchronization. The proposed adaptive importance-based sampling method jointly considers the graph structural heterogeneity and the optimization dynamics to achieve optimal trade-off between efficiency and accuracy. Extensive evaluations against five state-of-the-art baselines on five real-world graph datasets show that FedAIS achieves comparable or up to 3.23% higher test accuracy, while saving communication and computation costs by 91.77% and 85.59%.

Qianqian Xie, Qingyu Chen, Aokun Chen et al.

Recent advancements in large language models (LLMs) like ChatGPT and LLaMA show promise in medical applications, yet challenges remain in medical language comprehension. This study presents Me-LLaMA, a new medical LLM family based on open-source LLaMA models, optimized for medical text analysis and diagnosis by leveraging large-scale, domain-specific datasets. The Me-LLaMA family, including foundation models Me-LLaMA 13/70B and their chat-enhanced versions, was developed through continued pre-training and instruction tuning with 129B tokens and 214K samples from biomedical and clinical sources. Training the 70B models required over 100,000 A100 GPU hours. Me-LLaMA's performance was evaluated across six medical text analysis tasks using 12 benchmark datasets and complex clinical case diagnosis, with automatic and human evaluations. Results indicate Me-LLaMA outperforms LLaMA and other open-source medical LLMs in zero-shot and supervised settings. Task-specific tuning further boosts performance, surpassing ChatGPT on 7 of 8 datasets and GPT-4 on 5 of 8. For complex clinical cases, Me-LLaMA achieves performance comparable to ChatGPT and GPT-4. This work underscores the importance of domain-specific data in developing medical LLMs and addresses the high computational costs involved in training, highlighting a balance between pre-training and fine-tuning strategies. Me-LLaMA models are now accessible under user agreements, providing a valuable resource for advancing medical AI.

Jaehoon Yun, Jiwoong Sohn, Jungwoo Park et al.

Large language models have shown promise in clinical decision making, but current approaches struggle to localize and correct errors at specific steps of the reasoning process. This limitation is critical in medicine, where identifying and addressing reasoning errors is essential for accurate diagnosis and effective patient care. We introduce Med-PRM, a process reward modeling framework that leverages retrieval-augmented generation to verify each reasoning step against established medical knowledge bases. By verifying intermediate reasoning steps with evidence retrieved from clinical guidelines and literature, our model can precisely assess the reasoning quality in a fine-grained manner. Evaluations on five medical QA benchmarks and two open-ended diagnostic tasks demonstrate that Med-PRM achieves state-of-the-art performance, with improving the performance of base models by up to 13.50% using Med-PRM. Moreover, we demonstrate the generality of Med-PRM by integrating it in a plug-and-play fashion with strong policy models such as Meerkat, achieving over 80\% accuracy on MedQA for the first time using small-scale models of 8 billion parameters. Our code and data are available at: https://med-prm.github.io/

Nicholas Wan, Qiao Jin, Joey Chan et al.

Although large language models (LLMs) have been assessed for general medical knowledge using licensing exams, their ability to support clinical decision-making, such as selecting medical calculators, remains uncertain. We assessed nine LLMs, including open-source, proprietary, and domain-specific models, with 1,009 multiple-choice question-answer pairs across 35 clinical calculators and compared LLMs to humans on a subset of questions. While the highest-performing LLM, OpenAI o1, provided an answer accuracy of 66.0% (CI: 56.7-75.3%) on the subset of 100 questions, two human annotators nominally outperformed LLMs with an average answer accuracy of 79.5% (CI: 73.5-85.0%). Ultimately, we evaluated medical trainees and LLMs in recommending medical calculators across clinical scenarios like risk stratification and diagnosis. With error analysis showing that the highest-performing LLMs continue to make mistakes in comprehension (49.3% of errors) and calculator knowledge (7.1% of errors), our findings highlight that LLMs are not superior to humans in calculator recommendation.

Qingyu Chen, Yan Hu, Xueqing Peng et al.

The rapid growth of biomedical literature poses challenges for manual knowledge curation and synthesis. Biomedical Natural Language Processing (BioNLP) automates the process. While Large Language Models (LLMs) have shown promise in general domains, their effectiveness in BioNLP tasks remains unclear due to limited benchmarks and practical guidelines. We perform a systematic evaluation of four LLMs, GPT and LLaMA representatives on 12 BioNLP benchmarks across six applications. We compare their zero-shot, few-shot, and fine-tuning performance with traditional fine-tuning of BERT or BART models. We examine inconsistencies, missing information, hallucinations, and perform cost analysis. Here we show that traditional fine-tuning outperforms zero or few shot LLMs in most tasks. However, closed-source LLMs like GPT-4 excel in reasoning-related tasks such as medical question answering. Open source LLMs still require fine-tuning to close performance gaps. We find issues like missing information and hallucinations in LLM outputs. These results offer practical insights for applying LLMs in BioNLP.

Yifan Peng, Qingyu Chen, Zhiyong Lu

Multi-task learning (MTL) has achieved remarkable success in natural language processing applications. In this work, we study a multi-task learning model with multiple decoders on varieties of biomedical and clinical natural language processing tasks such as text similarity, relation extraction, named entity recognition, and text inference. Our empirical results demonstrate that the MTL fine-tuned models outperform state-of-the-art transformer models (e.g., BERT and its variants) by 2.0% and 1.3% in biomedical and clinical domains, respectively. Pairwise MTL further demonstrates more details about which tasks can improve or decrease others. This is particularly helpful in the context that researchers are in the hassle of choosing a suitable model for new problems. The code and models are publicly available at https://github.com/ncbi-nlp/bluebert

Qingyu Chen, Kyubum Lee, Shankai Yan et al.

Capturing the semantics of related biological concepts, such as genes and mutations, is of significant importance to many research tasks in computational biology such as protein-protein interaction detection, gene-drug association prediction, and biomedical literature-based discovery. Here, we propose to leverage state-of-the-art text mining tools and machine learning models to learn the semantics via vector representations (aka. embeddings) of over 400,000 biological concepts mentioned in the entire PubMed abstracts. Our learned embeddings, namely BioConceptVec, can capture related concepts based on their surrounding contextual information in the literature, which is beyond exact term match or co-occurrence-based methods. BioConceptVec has been thoroughly evaluated in multiple bioinformatics tasks consisting of over 25 million instances from nine different biological datasets. The evaluation results demonstrate that BioConceptVec has better performance than existing methods in all tasks. Finally, BioConceptVec is made freely available to the research community and general public via https://github.com/ncbi-nlp/BioConceptVec.

Tiarnan D. Keenan, Shazia Dharssi, Yifan Peng et al.

Purpose: To assess the utility of deep learning in the detection of geographic atrophy (GA) from color fundus photographs; secondary aim to explore potential utility in detecting central GA (CGA). Design: A deep learning model was developed to detect the presence of GA in color fundus photographs, and two additional models to detect CGA in different scenarios. Participants: 59,812 color fundus photographs from longitudinal follow up of 4,582 participants in the AREDS dataset. Gold standard labels were from human expert reading center graders using a standardized protocol. Methods: A deep learning model was trained to use color fundus photographs to predict GA presence from a population of eyes with no AMD to advanced AMD. A second model was trained to predict CGA presence from the same population. A third model was trained to predict CGA presence from the subset of eyes with GA. For training and testing, 5-fold cross-validation was employed. For comparison with human clinician performance, model performance was compared with that of 88 retinal specialists. Results: The deep learning models (GA detection, CGA detection from all eyes, and centrality detection from GA eyes) had AUC of 0.933-0.976, 0.939-0.976, and 0.827-0.888, respectively. The GA detection model had accuracy, sensitivity, specificity, and precision of 0.965, 0.692, 0.978, and 0.584, respectively. The CGA detection model had equivalent values of 0.966, 0.763, 0.971, and 0.394. The centrality detection model had equivalent values of 0.762, 0.782, 0.729, and 0.799. Conclusions: A deep learning model demonstrated high accuracy for the automated detection of GA. The AUC was non-inferior to that of human retinal specialists. Deep learning approaches may also be applied to the identification of CGA. The code and pretrained models are publicly available at https://github.com/ncbi-nlp/DeepSeeNet.

Yifan Peng, Shazia Dharssi, Qingyu Chen et al.

In assessing the severity of age-related macular degeneration (AMD), the Age-Related Eye Disease Study (AREDS) Simplified Severity Scale predicts the risk of progression to late AMD. However, its manual use requires the time-consuming participation of expert practitioners. Although several automated deep learning systems have been developed for classifying color fundus photographs (CFP) of individual eyes by AREDS severity score, none to date has used a patient-based scoring system that uses images from both eyes to assign a severity score. DeepSeeNet, a deep learning model, was developed to classify patients automatically by the AREDS Simplified Severity Scale (score 0-5) using bilateral CFP. DeepSeeNet was trained on 58,402 and tested on 900 images from the longitudinal follow-up of 4549 participants from AREDS. Gold standard labels were obtained using reading center grades. DeepSeeNet simulates the human grading process by first detecting individual AMD risk factors (drusen size, pigmentary abnormalities) for each eye and then calculating a patient-based AMD severity score using the AREDS Simplified Severity Scale. DeepSeeNet performed better on patient-based classification (accuracy = 0.671; kappa = 0.558) than retinal specialists (accuracy = 0.599; kappa = 0.467) with high AUC in the detection of large drusen (0.94), pigmentary abnormalities (0.93), and late AMD (0.97). DeepSeeNet demonstrated high accuracy with increased transparency in the automated assignment of individual patients to AMD risk categories based on the AREDS Simplified Severity Scale. These results highlight the potential of deep learning to assist and enhance clinical decision-making in patients with AMD, such as early AMD detection and risk prediction for developing late AMD. DeepSeeNet is publicly available on https://github.com/ncbi-nlp/DeepSeeNet.

Rui Yang, Haoran Liu, Edison Marrese-Taylor et al.

Large language models (LLMs) have demonstrated impressive generative capabilities with the potential to innovate in medicine. However, the application of LLMs in real clinical settings remains challenging due to the lack of factual consistency in the generated content. In this work, we develop an augmented LLM framework, KG-Rank, which leverages a medical knowledge graph (KG) along with ranking and re-ranking techniques, to improve the factuality of long-form question answering (QA) in the medical domain. Specifically, when receiving a question, KG-Rank automatically identifies medical entities within the question and retrieves the related triples from the medical KG to gather factual information. Subsequently, KG-Rank innovatively applies multiple ranking techniques to refine the ordering of these triples, providing more relevant and precise information for LLM inference. To the best of our knowledge, KG-Rank is the first application of KG combined with ranking models in medical QA specifically for generating long answers. Evaluation on four selected medical QA datasets demonstrates that KG-Rank achieves an improvement of over 18% in ROUGE-L score. Additionally, we extend KG-Rank to open domains, including law, business, music, and history, where it realizes a 14% improvement in ROUGE-L score, indicating the effectiveness and great potential of KG-Rank.

Weihao Xuan, Rui Yang, Heli Qi et al.

Existing large language model (LLM) evaluation benchmarks primarily focus on English, while current multilingual tasks lack parallel questions that specifically assess cross-linguistic reasoning abilities. This dual limitation makes it challenging to comprehensively assess LLMs' performance in the multilingual setting. To fill this gap, we introduce MMLU-ProX, a comprehensive benchmark covering 29 languages, built on an English benchmark. Each language version consists of 11,829 identical questions, enabling direct cross-linguistic comparisons. Additionally, to meet efficient evaluation needs, we provide a lite version containing 658 questions per language. To ensure the high quality of MMLU-ProX, we employ a rigorous development process that involves multiple powerful LLMs for translation, followed by expert review to ensure accurate expression, consistent terminology, and cultural relevance. Building on this, we systematically evaluate 36 state-of-the-art LLMs, including reasoning-enhanced and multilingual-optimized LLMs. The results reveal significant disparities in the multilingual capabilities of LLMs: While they perform well in high-resource languages, their performance declines markedly in low-resource languages, with gaps of up to 24.3%. Through MMLU-ProX, we aim to advance the development of more inclusive AI systems and promote equitable access to technology across global contexts.

Qiao Jin, Zhizheng Wang, Yifan Yang et al.

Clinical calculators play a vital role in healthcare by offering accurate evidence-based predictions for various purposes such as prognosis. Nevertheless, their widespread utilization is frequently hindered by usability challenges, poor dissemination, and restricted functionality. Augmenting large language models with extensive collections of clinical calculators presents an opportunity to overcome these obstacles and improve workflow efficiency, but the scalability of the manual curation process poses a significant challenge. In response, we introduce AgentMD, a novel language agent capable of curating and applying clinical calculators across various clinical contexts. Using the published literature, AgentMD has automatically curated a collection of 2,164 diverse clinical calculators with executable functions and structured documentation, collectively named RiskCalcs. Manual evaluations show that RiskCalcs tools achieve an accuracy of over 80% on three quality metrics. At inference time, AgentMD can automatically select and apply the relevant RiskCalcs tools given any patient description. On the newly established RiskQA benchmark, AgentMD significantly outperforms chain-of-thought prompting with GPT-4 (87.7% vs. 40.9% in accuracy). Additionally, we also applied AgentMD to real-world clinical notes for analyzing both population-level and risk-level patient characteristics. In summary, our study illustrates the utility of language agents augmented with clinical calculators for healthcare analytics and patient care.

Zhiyuan Wang, Jinhao Duan, Chenxi Yuan et al.

Uncertainty estimation is crucial for the reliability of safety-critical human and artificial intelligence (AI) interaction systems, particularly in the domain of healthcare engineering. However, a robust and general uncertainty measure for free-form answers has not been well-established in open-ended medical question-answering (QA) tasks, where generative inequality introduces a large number of irrelevant words and sequences within the generated set for uncertainty quantification (UQ), which can lead to biases. This paper introduces Word-Sequence Entropy (WSE), a method that calibrates uncertainty at both the word and sequence levels, considering semantic relevance. WSE quantifies uncertainty in a way that is more closely aligned with the reliability of LLMs during uncertainty quantification (UQ). We compare WSE with six baseline methods on five free-form medical QA datasets, utilizing seven popular large language models (LLMs). Experimental results demonstrate that WSE exhibits superior performance in UQ under two standard criteria for correctness evaluation. Additionally, in terms of real-world medical QA applications, the performance of LLMs is significantly enhanced (e.g., a 6.36% improvement in model accuracy on the COVID-QA dataset) by employing responses with lower uncertainty that are identified by WSE as final answers, without any additional task-specific fine-tuning or architectural modifications.

Pagnarasmey Pit, Xingjun Ma, Mike Conway et al.

Large Language Models (LLMs) have gained significant popularity for their application in various everyday tasks such as text generation, summarization, and information retrieval. As the widespread adoption of LLMs continues to surge, it becomes increasingly crucial to ensure that these models yield responses that are politically impartial, with the aim of preventing information bubbles, upholding fairness in representation, and mitigating confirmation bias. In this paper, we propose a quantitative framework and pipeline designed to systematically investigate the political orientation of LLMs. Our investigation delves into the political alignment of LLMs across a spectrum of eight polarizing topics, spanning from abortion to LGBTQ issues. Across topics, the results indicate that LLMs exhibit a tendency to provide responses that closely align with liberal or left-leaning perspectives rather than conservative or right-leaning ones when user queries include details pertaining to occupation, race, or political affiliation. The findings presented in this study not only reaffirm earlier observations regarding the left-leaning characteristics of LLMs but also surface particular attributes, such as occupation, that are particularly susceptible to such inclinations even when directly steered towards conservatism. As a recommendation to avoid these models providing politicised responses, users should be mindful when crafting queries, and exercise caution in selecting neutral prompt language.

Yingjian Chen, Haoran Liu, Yinhong Liu et al.

Large language models (LLMs) are widely used, but they often generate subtle factual errors, especially in long-form text. These errors are fatal in some specialized domains such as medicine. Existing fact-checking with grounding documents methods face two main challenges: (1) they struggle to understand complex multihop relations in long documents, often overlooking subtle factual errors; (2) most specialized methods rely on pairwise comparisons, requiring multiple model calls, leading to high resource and computational costs. To address these challenges, we propose GraphCheck, a fact-checking framework that uses extracted knowledge graphs to enhance text representation. Graph Neural Networks further process these graphs as a soft prompt, enabling LLMs to incorporate structured knowledge more effectively. Enhanced with graph-based reasoning, GraphCheck captures multihop reasoning chains that are often overlooked by existing methods, enabling precise and efficient fact-checking in a single inference call. Experimental results on seven benchmarks spanning both general and medical domains demonstrate up to a 7.1% overall improvement over baseline models. Notably, GraphCheck outperforms existing specialized fact-checkers and achieves comparable performance with state-of-the-art LLMs, such as DeepSeek-V3 and OpenAI-o1, with significantly fewer parameters.

Sahana Srinivasan, Xuguang Ai, Minjie Zou et al.

Question: What is the performance and reasoning ability of OpenAI o1 compared to other large language models in addressing ophthalmology-specific questions? Findings: This study evaluated OpenAI o1 and five LLMs using 6,990 ophthalmological questions from MedMCQA. O1 achieved the highest accuracy (0.88) and macro-F1 score but ranked third in reasoning capabilities based on text-generation metrics. Across subtopics, o1 ranked first in ``Lens'' and ``Glaucoma'' but second to GPT-4o in ``Corneal and External Diseases'', ``Vitreous and Retina'' and ``Oculoplastic and Orbital Diseases''. Subgroup analyses showed o1 performed better on queries with longer ground truth explanations. Meaning: O1's reasoning enhancements may not fully extend to ophthalmology, underscoring the need for domain-specific refinements to optimize performance in specialized fields like ophthalmology.

Minjie Zou, Sahana Srinivasan, Thaddaeus Wai Soon Lo et al.

Recent advances in reasoning-focused large language models (LLMs) mark a shift from general LLMs toward models designed for complex decision-making, a crucial aspect in medicine. However, their performance in specialized domains like ophthalmology remains underexplored. This study comprehensively evaluated and compared the accuracy and reasoning capabilities of four newly developed reasoning-focused LLMs, namely DeepSeek-R1, OpenAI o1, o3-mini, and Gemini 2.0 Flash-Thinking. Each model was assessed using 5,888 multiple-choice ophthalmology exam questions from the MedMCQA dataset in zero-shot setting. Quantitative evaluation included accuracy, Macro-F1, and five text-generation metrics (ROUGE-L, METEOR, BERTScore, BARTScore, and AlignScore), computed against ground-truth reasonings. Average inference time was recorded for a subset of 100 randomly selected questions. Additionally, two board-certified ophthalmologists qualitatively assessed clarity, completeness, and reasoning structure of responses to differential diagnosis questions.O1 (0.902) and DeepSeek-R1 (0.888) achieved the highest accuracy, with o1 also leading in Macro-F1 (0.900). The performance of models across the text-generation metrics varied: O3-mini excelled in ROUGE-L (0.151), o1 in METEOR (0.232), DeepSeek-R1 and o3-mini tied for BERTScore (0.673), DeepSeek-R1 (-4.105) and Gemini 2.0 Flash-Thinking (-4.127) performed best in BARTScore, while o3-mini (0.181) and o1 (0.176) led AlignScore. Inference time across the models varied, with DeepSeek-R1 being slowest (40.4 seconds) and Gemini 2.0 Flash-Thinking fastest (6.7 seconds). Qualitative evaluation revealed that DeepSeek-R1 and Gemini 2.0 Flash-Thinking tended to provide detailed and comprehensive intermediate reasoning, whereas o1 and o3-mini displayed concise and summarized justifications.

Jia Wei, Xiaoqi Zhao, Jonghye Woo et al.

Single domain generalization (SDG) has recently attracted growing attention in medical image segmentation. One promising strategy for SDG is to leverage consistent semantic shape priors across different imaging protocols, scanner vendors, and clinical sites. However, existing dictionary learning methods that encode shape priors often suffer from limited representational power with a small set of offline computed shape elements, or overfitting when the dictionary size grows. Moreover, they are not readily compatible with large foundation models such as the Segment Anything Model (SAM). In this paper, we propose a novel Mixture-of-Shape-Experts (MoSE) framework that seamlessly integrates the idea of mixture-of-experts (MoE) training into dictionary learning to efficiently capture diverse and robust shape priors. Our method conceptualizes each dictionary atom as a shape expert, which specializes in encoding distinct semantic shape information. A gating network dynamically fuses these shape experts into a robust shape map, with sparse activation guided by SAM encoding to prevent overfitting. We further provide this shape map as a prompt to SAM, utilizing the powerful generalization capability of SAM through bidirectional integration. All modules, including the shape dictionary, are trained in an end-to-end manner. Extensive experiments on multiple public datasets demonstrate its effectiveness.

Anran Li, Lingfei Qian, Mengmeng Du et al.

Large Language Models (LLMs) have demonstrated significant potential in medicine. To date, LLMs have been widely applied to tasks such as diagnostic assistance, medical question answering, and clinical information synthesis. However, a key open question remains: to what extent do LLMs memorize medical training data. In this study, we present the first comprehensive evaluation of memorization of LLMs in medicine, assessing its prevalence (how frequently it occurs), characteristics (what is memorized), volume (how much content is memorized), and potential downstream impacts (how memorization may affect medical applications). We systematically analyze common adaptation scenarios: (1) continued pretraining on medical corpora, (2) fine-tuning on standard medical benchmarks, and (3) fine-tuning on real-world clinical data, including over 13,000 unique inpatient records from Yale New Haven Health System. The results demonstrate that memorization is prevalent across all adaptation scenarios and significantly higher than reported in the general domain. Memorization affects both the development and adoption of LLMs in medicine and can be categorized into three types: beneficial (e.g., accurate recall of clinical guidelines and biomedical references), uninformative (e.g., repeated disclaimers or templated medical document language), and harmful (e.g., regeneration of dataset-specific or sensitive clinical content). Based on these findings, we offer practical recommendations to facilitate beneficial memorization that enhances domain-specific reasoning and factual accuracy, minimize uninformative memorization to promote deeper learning beyond surface-level patterns, and mitigate harmful memorization to prevent the leakage of sensitive or identifiable patient information.

Sahana Srinivasan, Xuguang Ai, Thaddaeus Wai Soon Lo et al.

Current benchmarks evaluating large language models (LLMs) in ophthalmology are limited in scope and disproportionately prioritise accuracy. We introduce BELO (BEnchmarking LLMs for Ophthalmology), a standardized and comprehensive evaluation benchmark developed through multiple rounds of expert checking by 13 ophthalmologists. BELO assesses ophthalmology-related clinical accuracy and reasoning quality. Using keyword matching and a fine-tuned PubMedBERT model, we curated ophthalmology-specific multiple-choice-questions (MCQs) from diverse medical datasets (BCSC, MedMCQA, MedQA, BioASQ, and PubMedQA). The dataset underwent multiple rounds of expert checking. Duplicate and substandard questions were systematically removed. Ten ophthalmologists refined the explanations of each MCQ's correct answer. This was further adjudicated by three senior ophthalmologists. To illustrate BELO's utility, we evaluated six LLMs (OpenAI o1, o3-mini, GPT-4o, DeepSeek-R1, Llama-3-8B, and Gemini 1.5 Pro) using accuracy, macro-F1, and five text-generation metrics (ROUGE-L, BERTScore, BARTScore, METEOR, and AlignScore). In a further evaluation involving human experts, two ophthalmologists qualitatively reviewed 50 randomly selected outputs for accuracy, comprehensiveness, and completeness. BELO consists of 900 high-quality, expert-reviewed questions aggregated from five sources: BCSC (260), BioASQ (10), MedMCQA (572), MedQA (40), and PubMedQA (18). A public leaderboard has been established to promote transparent evaluation and reporting. Importantly, the BELO dataset will remain a hold-out, evaluation-only benchmark to ensure fair and reproducible comparisons of future models.

Nikhil Khandekar, Qiao Jin, Guangzhi Xiong et al.

As opposed to evaluating computation and logic-based reasoning, current benchmarks for evaluating large language models (LLMs) in medicine are primarily focused on question-answering involving domain knowledge and descriptive reasoning. While such qualitative capabilities are vital to medical diagnosis, in real-world scenarios, doctors frequently use clinical calculators that follow quantitative equations and rule-based reasoning paradigms for evidence-based decision support. To this end, we propose MedCalc-Bench, a first-of-its-kind dataset focused on evaluating the medical calculation capability of LLMs. MedCalc-Bench contains an evaluation set of over 1000 manually reviewed instances from 55 different medical calculation tasks. Each instance in MedCalc-Bench consists of a patient note, a question requesting to compute a specific medical value, a ground truth answer, and a step-by-step explanation showing how the answer is obtained. While our evaluation results show the potential of LLMs in this area, none of them are effective enough for clinical settings. Common issues include extracting the incorrect entities, not using the correct equation or rules for a calculation task, or incorrectly performing the arithmetic for the computation. We hope our study highlights the quantitative knowledge and reasoning gaps in LLMs within medical settings, encouraging future improvements of LLMs for various clinical calculation tasks.

Yu Yin, Hyunjae Kim, Xiao Xiao et al.

Training a neural network-based biomedical named entity recognition (BioNER) model usually requires extensive and costly human annotations. While several studies have employed multi-task learning with multiple BioNER datasets to reduce human effort, this approach does not consistently yield performance improvements and may introduce label ambiguity in different biomedical corpora. We aim to tackle those challenges through transfer learning from easily accessible resources with fewer concept overlaps with biomedical datasets. We proposed GERBERA, a simple-yet-effective method that utilized general-domain NER datasets for training. We performed multi-task learning to train a pre-trained biomedical language model with both the target BioNER dataset and the general-domain dataset. Subsequently, we fine-tuned the models specifically for the BioNER dataset. We systematically evaluated GERBERA on five datasets of eight entity types, collectively consisting of 81,410 instances. Despite using fewer biomedical resources, our models demonstrated superior performance compared to baseline models trained with additional BioNER datasets. Specifically, our models consistently outperformed the baseline models in six out of eight entity types, achieving an average improvement of 0.9% over the best baseline performance across eight entities. Our method was especially effective in amplifying performance on BioNER datasets characterized by limited data, with a 4.7% improvement in F1 scores on the JNLPBA-RNA dataset. This study introduces a new training method that leverages cost-effective general-domain NER datasets to augment BioNER models. This approach significantly improves BioNER model performance, making it a valuable asset for scenarios with scarce or costly biomedical datasets.

Chih-Hsuan Wei, Alexis Allot, Po-Ting Lai et al.

PubTator 3.0 (https://www.ncbi.nlm.nih.gov/research/pubtator3/) is a biomedical literature resource using state-of-the-art AI techniques to offer semantic and relation searches for key concepts like proteins, genetic variants, diseases, and chemicals. It currently provides over one billion entity and relation annotations across approximately 36 million PubMed abstracts and 6 million full-text articles from the PMC open access subset, updated weekly. PubTator 3.0's online interface and API utilize these precomputed entity relations and synonyms to provide advanced search capabilities and enable large-scale analyses, streamlining many complex information needs. We showcase the retrieval quality of PubTator 3.0 using a series of entity pair queries, demonstrating that PubTator 3.0 retrieves a greater number of articles than either PubMed or Google Scholar, with higher precision in the top 20 results. We further show that integrating ChatGPT (GPT-4) with PubTator APIs dramatically improves the factuality and verifiability of its responses. In summary, PubTator 3.0 offers a comprehensive set of features and tools that allow researchers to navigate the ever-expanding wealth of biomedical literature, expediting research and unlocking valuable insights for scientific discovery.

Qiyuan An, Ruijiang Li, Lin Gu et al.

Unsupervised domain adaptation (UDA) generally aligns the unlabeled target domain data to the distribution of the source domain to mitigate the distribution shift problem. The standard UDA requires sharing the source data with the target, having potential data privacy leaking risks. To protect the source data's privacy, we first propose to share the source feature distribution instead of the source data. However, sharing only the source feature distribution may still suffer from the membership inference attack who can infer an individual's membership by the black-box access to the source model. To resolve this privacy issue, we further study the under-explored problem of privacy-preserving domain adaptation and propose a method with a novel differential privacy training strategy to protect the source data privacy. We model the source feature distribution by Gaussian Mixture Models (GMMs) under the differential privacy setting and send it to the target client for adaptation. The target client resamples differentially private source features from GMMs and adapts on target data with several state-of-art UDA backbones. With our proposed method, the source data provider could avoid leaking source data privacy during domain adaptation as well as reserve the utility. To evaluate our proposed method's utility and privacy loss, we apply our model on a medical report disease label classification task using two noisy challenging clinical text datasets. The results show that our proposed method can preserve source data's privacy with a minor performance influence on the text classification task.

Qingyu Chen, Tiarnan D. L. Keenan, Alexis Allot et al.

Objective Reticular pseudodrusen (RPD), a key feature of age-related macular degeneration (AMD), are poorly detected by human experts on standard color fundus photography (CFP) and typically require advanced imaging modalities such as fundus autofluorescence (FAF). The objective was to develop and evaluate the performance of a novel 'M3' deep learning framework on RPD detection. Materials and Methods A deep learning framework M3 was developed to detect RPD presence accurately using CFP alone, FAF alone, or both, employing >8000 CFP-FAF image pairs obtained prospectively (Age-Related Eye Disease Study 2). The M3 framework includes multi-modal (detection from single or multiple image modalities), multi-task (training different tasks simultaneously to improve generalizability), and multi-attention (improving ensembled feature representation) operation. Performance on RPD detection was compared with state-of-the-art deep learning models and 13 ophthalmologists; performance on detection of two other AMD features (geographic atrophy and pigmentary abnormalities) was also evaluated. Results For RPD detection, M3 achieved area under receiver operating characteristic (AUROC) 0.832, 0.931, and 0.933 for CFP alone, FAF alone, and both, respectively. M3 performance on CFP was very substantially superior to human retinal specialists (median F1-score 0.644 versus 0.350). External validation (on Rotterdam Study, Netherlands) demonstrated high accuracy on CFP alone (AUROC 0.965). The M3 framework also accurately detected geographic atrophy and pigmentary abnormalities (AUROC 0.909 and 0.912, respectively), demonstrating its generalizability. Conclusion This study demonstrates the successful development, robust evaluation, and external validation of a novel deep learning framework that enables accessible, accurate, and automated AMD diagnosis and prognosis.

Yifan Peng, Tiarnan D. Keenan, Qingyu Chen et al.

By 2040, age-related macular degeneration (AMD) will affect approximately 288 million people worldwide. Identifying individuals at high risk of progression to late AMD, the sight-threatening stage, is critical for clinical actions, including medical interventions and timely monitoring. Although deep learning has shown promise in diagnosing/screening AMD using color fundus photographs, it remains difficult to predict individuals' risks of late AMD accurately. For both tasks, these initial deep learning attempts have remained largely unvalidated in independent cohorts. Here, we demonstrate how deep learning and survival analysis can predict the probability of progression to late AMD using 3,298 participants (over 80,000 images) from the Age-Related Eye Disease Studies AREDS and AREDS2, the largest longitudinal clinical trials in AMD. When validated against an independent test dataset of 601 participants, our model achieved high prognostic accuracy (five-year C-statistic 86.4 (95% confidence interval 86.2-86.6)) that substantially exceeded that of retinal specialists using two existing clinical standards (81.3 (81.1-81.5) and 82.0 (81.8-82.3), respectively). Interestingly, our approach offers additional strengths over the existing clinical standards in AMD prognosis (e.g., risk ascertainment above 50%) and is likely to be highly generalizable, given the breadth of training data from 82 US retinal specialty clinics. Indeed, during external validation through training on AREDS and testing on AREDS2 as an independent cohort, our model retained substantially higher prognostic accuracy than existing clinical standards. These results highlight the potential of deep learning systems to enhance clinical decision-making in AMD patients.

Qingyu Chen, Jingcheng Du, Sun Kim et al.

Capturing sentence semantics plays a vital role in a range of text mining applications. Despite continuous efforts on the development of related datasets and models in the general domain, both datasets and models are limited in biomedical and clinical domains. The BioCreative/OHNLP organizers have made the first attempt to annotate 1,068 sentence pairs from clinical notes and have called for a community effort to tackle the Semantic Textual Similarity (BioCreative/OHNLP STS) challenge. We developed models using traditional machine learning and deep learning approaches. For the post challenge, we focus on two models: the Random Forest and the Encoder Network. We applied sentence embeddings pre-trained on PubMed abstracts and MIMIC-III clinical notes and updated the Random Forest and the Encoder Network accordingly. The official results demonstrated our best submission was the ensemble of eight models. It achieved a Person correlation coefficient of 0.8328, the highest performance among 13 submissions from 4 teams. For the post challenge, the performance of both Random Forest and the Encoder Network was improved; in particular, the correlation of the Encoder Network was improved by ~13%. During the challenge task, no end-to-end deep learning models had better performance than machine learning models that take manually-crafted features. In contrast, with the sentence embeddings pre-trained on biomedical corpora, the Encoder Network now achieves a correlation of ~0.84, which is higher than the original best model. The ensembled model taking the improved versions of the Random Forest and Encoder Network as inputs further increased performance to 0.8528. Deep learning models with sentence embeddings pre-trained on biomedical corpora achieve the highest performance on the test set.

Qingyu Chen, Yifan Peng, Tiarnan Keenan et al.

Age-related Macular Degeneration (AMD) is a leading cause of blindness. Although the Age-Related Eye Disease Study group previously developed a 9-step AMD severity scale for manual classification of AMD severity from color fundus images, manual grading of images is time-consuming and expensive. Built on our previous work DeepSeeNet, we developed a novel deep learning model for automated classification of images into the 9-step scale. Instead of predicting the 9-step score directly, our approach simulates the reading center grading process. It first detects four AMD characteristics (drusen area, geographic atrophy, increased pigment, and depigmentation), then combines these to derive the overall 9-step score. Importantly, we applied multi-task learning techniques, which allowed us to train classification of the four characteristics in parallel, share representation, and prevent overfitting. Evaluation on two image datasets showed that the accuracy of the model exceeded the current state-of-the-art model by > 10%.

Jingcheng Du, Qingyu Chen, Yifan Peng et al.

In multi-label text classification, each textual document can be assigned with one or more labels. Due to this nature, the multi-label text classification task is often considered to be more challenging compared to the binary or multi-class text classification problems. As an important task with broad applications in biomedicine such as assigning diagnosis codes, a number of different computational methods (e.g. training and combining binary classifiers for each label) have been proposed in recent years. However, many suffered from modest accuracy and efficiency, with only limited success in practical use. We propose ML-Net, a novel deep learning framework, for multi-label classification of biomedical texts. As an end-to-end system, ML-Net combines a label prediction network with an automated label count prediction mechanism to output an optimal set of labels by leveraging both predicted confidence score of each label and the contextual information in the target document. We evaluate ML-Net on three independent, publicly-available corpora in two kinds of text genres: biomedical literature and clinical notes. For evaluation, example-based measures such as precision, recall and f-measure are used. ML-Net is compared with several competitive machine learning baseline models. Our benchmarking results show that ML-Net compares favorably to the state-of-the-art methods in multi-label classification of biomedical texts. ML-NET is also shown to be robust when evaluated on different text genres in biomedicine. Unlike traditional machine learning methods, ML-Net does not require human efforts in feature engineering and is highly efficient and scalable approach to tasks with a large set of labels (no need to build individual classifiers for each separate label). Finally, ML-NET is able to dynamically estimate the label count based on the document context in a more systematic and accurate manner.