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Jun 9

Biomedical Language Models are Robust to Sub-optimal Tokenization

As opposed to general English, many concepts in biomedical terminology have been designed in recent history by biomedical professionals with the goal of being precise and concise. This is often achieved by concatenating meaningful biomedical morphemes to create new semantic units. Nevertheless, most modern biomedical language models (LMs) are pre-trained using standard domain-specific tokenizers derived from large scale biomedical corpus statistics without explicitly leveraging the agglutinating nature of biomedical language. In this work, we first find that standard open-domain and biomedical tokenizers are largely unable to segment biomedical terms into meaningful components. Therefore, we hypothesize that using a tokenizer which segments biomedical terminology more accurately would enable biomedical LMs to improve their performance on downstream biomedical NLP tasks, especially ones which involve biomedical terms directly such as named entity recognition (NER) and entity linking. Surprisingly, we find that pre-training a biomedical LM using a more accurate biomedical tokenizer does not improve the entity representation quality of a language model as measured by several intrinsic and extrinsic measures such as masked language modeling prediction (MLM) accuracy as well as NER and entity linking performance. These quantitative findings, along with a case study which explores entity representation quality more directly, suggest that the biomedical pre-training process is quite robust to instances of sub-optimal tokenization.

  • 3 authors
·
Jun 30, 2023

BIOptimus: Pre-training an Optimal Biomedical Language Model with Curriculum Learning for Named Entity Recognition

Using language models (LMs) pre-trained in a self-supervised setting on large corpora and then fine-tuning for a downstream task has helped to deal with the problem of limited label data for supervised learning tasks such as Named Entity Recognition (NER). Recent research in biomedical language processing has offered a number of biomedical LMs pre-trained using different methods and techniques that advance results on many BioNLP tasks, including NER. However, there is still a lack of a comprehensive comparison of pre-training approaches that would work more optimally in the biomedical domain. This paper aims to investigate different pre-training methods, such as pre-training the biomedical LM from scratch and pre-training it in a continued fashion. We compare existing methods with our proposed pre-training method of initializing weights for new tokens by distilling existing weights from the BERT model inside the context where the tokens were found. The method helps to speed up the pre-training stage and improve performance on NER. In addition, we compare how masking rate, corruption strategy, and masking strategies impact the performance of the biomedical LM. Finally, using the insights from our experiments, we introduce a new biomedical LM (BIOptimus), which is pre-trained using Curriculum Learning (CL) and contextualized weight distillation method. Our model sets new states of the art on several biomedical Named Entity Recognition (NER) tasks. We release our code and all pre-trained models

  • 2 authors
·
Aug 16, 2023

Domain-Specific Language Model Pretraining for Biomedical Natural Language Processing

Pretraining large neural language models, such as BERT, has led to impressive gains on many natural language processing (NLP) tasks. However, most pretraining efforts focus on general domain corpora, such as newswire and Web. A prevailing assumption is that even domain-specific pretraining can benefit by starting from general-domain language models. In this paper, we challenge this assumption by showing that for domains with abundant unlabeled text, such as biomedicine, pretraining language models from scratch results in substantial gains over continual pretraining of general-domain language models. To facilitate this investigation, we compile a comprehensive biomedical NLP benchmark from publicly-available datasets. Our experiments show that domain-specific pretraining serves as a solid foundation for a wide range of biomedical NLP tasks, leading to new state-of-the-art results across the board. Further, in conducting a thorough evaluation of modeling choices, both for pretraining and task-specific fine-tuning, we discover that some common practices are unnecessary with BERT models, such as using complex tagging schemes in named entity recognition (NER). To help accelerate research in biomedical NLP, we have released our state-of-the-art pretrained and task-specific models for the community, and created a leaderboard featuring our BLURB benchmark (short for Biomedical Language Understanding & Reasoning Benchmark) at https://aka.ms/BLURB.

  • 9 authors
·
Jul 30, 2020 1

Localising In-Domain Adaptation of Transformer-Based Biomedical Language Models

In the era of digital healthcare, the huge volumes of textual information generated every day in hospitals constitute an essential but underused asset that could be exploited with task-specific, fine-tuned biomedical language representation models, improving patient care and management. For such specialized domains, previous research has shown that fine-tuning models stemming from broad-coverage checkpoints can largely benefit additional training rounds over large-scale in-domain resources. However, these resources are often unreachable for less-resourced languages like Italian, preventing local medical institutions to employ in-domain adaptation. In order to reduce this gap, our work investigates two accessible approaches to derive biomedical language models in languages other than English, taking Italian as a concrete use-case: one based on neural machine translation of English resources, favoring quantity over quality; the other based on a high-grade, narrow-scoped corpus natively written in Italian, thus preferring quality over quantity. Our study shows that data quantity is a harder constraint than data quality for biomedical adaptation, but the concatenation of high-quality data can improve model performance even when dealing with relatively size-limited corpora. The models published from our investigations have the potential to unlock important research opportunities for Italian hospitals and academia. Finally, the set of lessons learned from the study constitutes valuable insights towards a solution to build biomedical language models that are generalizable to other less-resourced languages and different domain settings.

  • 5 authors
·
Dec 20, 2022

BioBERT: a pre-trained biomedical language representation model for biomedical text mining

Biomedical text mining is becoming increasingly important as the number of biomedical documents rapidly grows. With the progress in natural language processing (NLP), extracting valuable information from biomedical literature has gained popularity among researchers, and deep learning has boosted the development of effective biomedical text mining models. However, directly applying the advancements in NLP to biomedical text mining often yields unsatisfactory results due to a word distribution shift from general domain corpora to biomedical corpora. In this article, we investigate how the recently introduced pre-trained language model BERT can be adapted for biomedical corpora. We introduce BioBERT (Bidirectional Encoder Representations from Transformers for Biomedical Text Mining), which is a domain-specific language representation model pre-trained on large-scale biomedical corpora. With almost the same architecture across tasks, BioBERT largely outperforms BERT and previous state-of-the-art models in a variety of biomedical text mining tasks when pre-trained on biomedical corpora. While BERT obtains performance comparable to that of previous state-of-the-art models, BioBERT significantly outperforms them on the following three representative biomedical text mining tasks: biomedical named entity recognition (0.62% F1 score improvement), biomedical relation extraction (2.80% F1 score improvement) and biomedical question answering (12.24% MRR improvement). Our analysis results show that pre-training BERT on biomedical corpora helps it to understand complex biomedical texts. We make the pre-trained weights of BioBERT freely available at https://github.com/naver/biobert-pretrained, and the source code for fine-tuning BioBERT available at https://github.com/dmis-lab/biobert.

  • 7 authors
·
Jan 25, 2019

Is Biomedical Specialization Still Worth It? Insights from Domain-Adaptive Language Modelling with a New French Health Corpus

Large language models (LLMs) have demonstrated remarkable capabilities across diverse domains, yet their adaptation to specialized fields remains challenging, particularly for non-English languages. This study investigates domain-adaptive pre-training (DAPT) as a strategy for specializing small to mid-sized LLMs in the French biomedical domain through continued pre-training. We address two key research questions: the viability of specialized continued pre-training for domain adaptation and the relationship between domain-specific performance gains and general capability degradation. Our contributions include the release of a fully open-licensed French biomedical corpus suitable for commercial and open-source applications, the training and release of specialized French biomedical LLMs, and novel insights for DAPT implementation. Our methodology encompasses the collection and refinement of high-quality French biomedical texts, the exploration of causal language modeling approaches using DAPT, and conducting extensive comparative evaluations. Our results cast doubt on the efficacy of DAPT, in contrast to previous works, but we highlight its viability in smaller-scale, resource-constrained scenarios under the right conditions. Findings in this paper further suggest that model merging post-DAPT is essential to mitigate generalization trade-offs, and in some cases even improves performance on specialized tasks at which the DAPT was directed.

  • 8 authors
·
Apr 7

Exploring the Effectiveness of Instruction Tuning in Biomedical Language Processing

Large Language Models (LLMs), particularly those similar to ChatGPT, have significantly influenced the field of Natural Language Processing (NLP). While these models excel in general language tasks, their performance in domain-specific downstream tasks such as biomedical and clinical Named Entity Recognition (NER), Relation Extraction (RE), and Medical Natural Language Inference (NLI) is still evolving. In this context, our study investigates the potential of instruction tuning for biomedical language processing, applying this technique to two general LLMs of substantial scale. We present a comprehensive, instruction-based model trained on a dataset that consists of approximately 200,000 instruction-focused samples. This dataset represents a carefully curated compilation of existing data, meticulously adapted and reformatted to align with the specific requirements of our instruction-based tasks. This initiative represents an important step in utilising such models to achieve results on par with specialised encoder-only models like BioBERT and BioClinicalBERT for various classical biomedical NLP tasks. Our work includes an analysis of the dataset's composition and its impact on model performance, providing insights into the intricacies of instruction tuning. By sharing our codes, models, and the distinctively assembled instruction-based dataset, we seek to encourage ongoing research and development in this area.

  • 3 authors
·
Dec 31, 2023

Label Dependent Attention Model for Disease Risk Prediction Using Multimodal Electronic Health Records

Disease risk prediction has attracted increasing attention in the field of modern healthcare, especially with the latest advances in artificial intelligence (AI). Electronic health records (EHRs), which contain heterogeneous patient information, are widely used in disease risk prediction tasks. One challenge of applying AI models for risk prediction lies in generating interpretable evidence to support the prediction results while retaining the prediction ability. In order to address this problem, we propose the method of jointly embedding words and labels whereby attention modules learn the weights of words from medical notes according to their relevance to the names of risk prediction labels. This approach boosts interpretability by employing an attention mechanism and including the names of prediction tasks in the model. However, its application is only limited to the handling of textual inputs such as medical notes. In this paper, we propose a label dependent attention model LDAM to 1) improve the interpretability by exploiting Clinical-BERT (a biomedical language model pre-trained on a large clinical corpus) to encode biomedically meaningful features and labels jointly; 2) extend the idea of joint embedding to the processing of time-series data, and develop a multi-modal learning framework for integrating heterogeneous information from medical notes and time-series health status indicators. To demonstrate our method, we apply LDAM to the MIMIC-III dataset to predict different disease risks. We evaluate our method both quantitatively and qualitatively. Specifically, the predictive power of LDAM will be shown, and case studies will be carried out to illustrate its interpretability.

  • 5 authors
·
Jan 18, 2022

Correlation Is Not Enough: Embedding Human Metadata for Individual Causal Discovery

Ask a pretrained biomedical language model whether "cortisol 28 ug/dL" and "stock-market volatility" are related, and it returns a cosine similarity of 0.83 on a scale where 1.0 means identical. The two share no mechanism. This is not a corner case: every off-the-shelf biomedical encoder we tested (BioBERT, PubMedBERT, BioM-ELECTRA) scores unrelated cross-domain pairs between 0.76 and 0.92 when the answer should be near zero. Accuracy on cross-domain discrimination is 0%. Retrieval systems survive this, because a language model downstream filters the noise. A Large Behavioural Model (LBM), a foundation model whose subject is a person rather than a sentence, does not: it reasons over a graph of a user's life and treats embedding proximity as evidence that two events are causally linked. False proximity writes a false causal edge, and everything downstream inherits the error. Here, embedding geometry is not a tuning knob; it is correctness. We report the fix. A contrastive pass over 72,034 pairs raises PubMedBERT BIOSSES correlation from 0.633 to 0.828 and within-vs-across-domain separation from 1.05x to 1.63x. A second pass, BODHI, mines hard negatives from edges absent in a biomedical knowledge graph and lifts separation to 2.30x and the discrimination gap to +0.392, at a 4.5% BIOSSES cost. On an Intel Xeon 6737P with AMX, OpenVINO cuts single-query latency from 1367 ms to 10 ms (133x) and reaches 555 sentences/sec. One finding contradicts standard advice: FP16 beats INT8 on this silicon at every serving batch size, and we explain why. The same model on a no-AMX Ice Lake instance runs 13-27x slower. We release the benchmark suite, training corpora, the BODHI generator, and the OpenVINO scripts.

  • 3 authors
·
Jun 7

Benchmarking Retrieval-Augmented Large Language Models in Biomedical NLP: Application, Robustness, and Self-Awareness

Large language models (LLM) have demonstrated remarkable capabilities in various biomedical natural language processing (NLP) tasks, leveraging the demonstration within the input context to adapt to new tasks. However, LLM is sensitive to the selection of demonstrations. To address the hallucination issue inherent in LLM, retrieval-augmented LLM (RAL) offers a solution by retrieving pertinent information from an established database. Nonetheless, existing research work lacks rigorous evaluation of the impact of retrieval-augmented large language models on different biomedical NLP tasks. This deficiency makes it challenging to ascertain the capabilities of RAL within the biomedical domain. Moreover, the outputs from RAL are affected by retrieving the unlabeled, counterfactual, or diverse knowledge that is not well studied in the biomedical domain. However, such knowledge is common in the real world. Finally, exploring the self-awareness ability is also crucial for the RAL system. So, in this paper, we systematically investigate the impact of RALs on 5 different biomedical tasks (triple extraction, link prediction, classification, question answering, and natural language inference). We analyze the performance of RALs in four fundamental abilities, including unlabeled robustness, counterfactual robustness, diverse robustness, and negative awareness. To this end, we proposed an evaluation framework to assess the RALs' performance on different biomedical NLP tasks and establish four different testbeds based on the aforementioned fundamental abilities. Then, we evaluate 3 representative LLMs with 3 different retrievers on 5 tasks over 9 datasets.

  • 6 authors
·
May 13, 2024

Fine-Tuning Large Neural Language Models for Biomedical Natural Language Processing

Motivation: A perennial challenge for biomedical researchers and clinical practitioners is to stay abreast with the rapid growth of publications and medical notes. Natural language processing (NLP) has emerged as a promising direction for taming information overload. In particular, large neural language models facilitate transfer learning by pretraining on unlabeled text, as exemplified by the successes of BERT models in various NLP applications. However, fine-tuning such models for an end task remains challenging, especially with small labeled datasets, which are common in biomedical NLP. Results: We conduct a systematic study on fine-tuning stability in biomedical NLP. We show that finetuning performance may be sensitive to pretraining settings, especially in low-resource domains. Large models have potential to attain better performance, but increasing model size also exacerbates finetuning instability. We thus conduct a comprehensive exploration of techniques for addressing fine-tuning instability. We show that these techniques can substantially improve fine-tuning performance for lowresource biomedical NLP applications. Specifically, freezing lower layers is helpful for standard BERT-BASE models, while layerwise decay is more effective for BERT-LARGE and ELECTRA models. For low-resource text similarity tasks such as BIOSSES, reinitializing the top layer is the optimal strategy. Overall, domainspecific vocabulary and pretraining facilitate more robust models for fine-tuning. Based on these findings, we establish new state of the art on a wide range of biomedical NLP applications. Availability and implementation: To facilitate progress in biomedical NLP, we release our state-of-the-art pretrained and fine-tuned models: https://aka.ms/BLURB.

  • 8 authors
·
Dec 14, 2021

BiomedCoOp: Learning to Prompt for Biomedical Vision-Language Models

Recent advancements in vision-language models (VLMs), such as CLIP, have demonstrated substantial success in self-supervised representation learning for vision tasks. However, effectively adapting VLMs to downstream applications remains challenging, as their accuracy often depends on time-intensive and expertise-demanding prompt engineering, while full model fine-tuning is costly. This is particularly true for biomedical images, which, unlike natural images, typically suffer from limited annotated datasets, unintuitive image contrasts, and nuanced visual features. Recent prompt learning techniques, such as Context Optimization (CoOp) intend to tackle these issues, but still fall short in generalizability. Meanwhile, explorations in prompt learning for biomedical image analysis are still highly limited. In this work, we propose BiomedCoOp, a novel prompt learning framework that enables efficient adaptation of BiomedCLIP for accurate and highly generalizable few-shot biomedical image classification. Our approach achieves effective prompt context learning by leveraging semantic consistency with average prompt ensembles from Large Language Models (LLMs) and knowledge distillation with a statistics-based prompt selection strategy. We conducted comprehensive validation of our proposed framework on 11 medical datasets across 9 modalities and 10 organs against existing state-of-the-art methods, demonstrating significant improvements in both accuracy and generalizability. The code is publicly available at https://github.com/HealthX-Lab/BiomedCoOp.

  • 4 authors
·
Nov 21, 2024

BioInstruct: Instruction Tuning of Large Language Models for Biomedical Natural Language Processing

To enhance the performance of large language models (LLMs) in biomedical natural language processing (BioNLP) by introducing a domain-specific instruction dataset and examining its impact when combined with multi-task learning principles. We created the BioInstruct, comprising 25,005 instructions to instruction-tune LLMs(LLaMA 1 & 2, 7B & 13B version). The instructions were created by prompting the GPT-4 language model with three-seed samples randomly drawn from an 80 human curated instructions. We employed Low-Rank Adaptation(LoRA) for parameter-efficient fine-tuning. We then evaluated these instruction-tuned LLMs on several BioNLP tasks, which can be grouped into three major categories: question answering(QA), information extraction(IE), and text generation(GEN). We also examined whether categories(e.g., QA, IE, and generation) of instructions impact model performance. Comparing with LLMs without instruction-tuned, our instruction-tuned LLMs demonstrated marked performance gains: 17.3% in QA, 5.7% in IE, and 96% in Generation tasks. Our 7B-parameter instruction-tuned LLaMA 1 model was competitive or even surpassed other LLMs in the biomedical domain that were also fine-tuned from LLaMA 1 with vast domain-specific data or a variety of tasks. Our results also show that the performance gain is significantly higher when instruction fine-tuning is conducted with closely related tasks. Our findings align with the observations of multi-task learning, suggesting the synergies between two tasks. The BioInstruct dataset serves as a valuable resource and instruction tuned LLMs lead to the best performing BioNLP applications.

  • 4 authors
·
Oct 30, 2023

Evi-Steer: Learning to Steer Biomedical Vision-Language Models through Efficient and Generalizable Evidential Tuning

Parameter-efficient adaptation of vision-language foundation models is crucial for precise multimodal understanding of biomedical images, yet existing methods remain deterministic and often struggle under domain shift or ambiguous image-text alignment. This limitation is particularly critical in the clinic, where models should remain robust in low-data regimes and domain shifts. We present Evi-Steer, an evidential cross-modal low-dimensional steering framework for BiomedCLIP that enables uncertainty-aware parameter-efficient fine-tuning while updating only 0.11% of total model parameters. Our approach performs lightweight low-dimensional token updates in both vision and text encoders while simultaneously estimating epistemic uncertainty. These uncertainty estimates update gate residuals, allowing the model to adapt conservatively when evidence is weak. Furthermore, we introduce cross-modal confidence fusion based on Dempster-Shafer theory, enabling visual adaptation to be conditioned on textual confidence and suppressing conflicting or uncertain cross-modal updates. We conduct a comprehensive evaluation on 15 biomedical imaging datasets spanning 8 organs and 8 imaging modalities under few-shot learning and domain generalization settings. Evi-Steer consistently outperforms state-of-the-art methods under few-shot learning and domain shift settings, demonstrating a practical and robust pathway for deploying vision-language models in real-world clinical settings. Code is available at https://github.com/HealthX-Lab/Evi-Steer.

  • 3 authors
·
May 24

Making the Most of Text Semantics to Improve Biomedical Vision--Language Processing

Multi-modal data abounds in biomedicine, such as radiology images and reports. Interpreting this data at scale is essential for improving clinical care and accelerating clinical research. Biomedical text with its complex semantics poses additional challenges in vision--language modelling compared to the general domain, and previous work has used insufficiently adapted models that lack domain-specific language understanding. In this paper, we show that principled textual semantic modelling can substantially improve contrastive learning in self-supervised vision--language processing. We release a language model that achieves state-of-the-art results in radiology natural language inference through its improved vocabulary and novel language pretraining objective leveraging semantics and discourse characteristics in radiology reports. Further, we propose a self-supervised joint vision--language approach with a focus on better text modelling. It establishes new state of the art results on a wide range of publicly available benchmarks, in part by leveraging our new domain-specific language model. We release a new dataset with locally-aligned phrase grounding annotations by radiologists to facilitate the study of complex semantic modelling in biomedical vision--language processing. A broad evaluation, including on this new dataset, shows that our contrastive learning approach, aided by textual-semantic modelling, outperforms prior methods in segmentation tasks, despite only using a global-alignment objective.

  • 12 authors
·
Apr 20, 2022

RAD-DINO: Exploring Scalable Medical Image Encoders Beyond Text Supervision

Language-supervised pre-training has proven to be a valuable method for extracting semantically meaningful features from images, serving as a foundational element in multimodal systems within the computer vision and medical imaging domains. However, resulting features are limited by the information contained within the text. This is particularly problematic in medical imaging, where radiologists' written findings focus on specific observations; a challenge compounded by the scarcity of paired imaging-text data due to concerns over leakage of personal health information. In this work, we fundamentally challenge the prevailing reliance on language supervision for learning general purpose biomedical imaging encoders. We introduce RAD-DINO, a biomedical image encoder pre-trained solely on unimodal biomedical imaging data that obtains similar or greater performance than state-of-the-art biomedical language supervised models on a diverse range of benchmarks. Specifically, the quality of learned representations is evaluated on standard imaging tasks (classification and semantic segmentation), and a vision-language alignment task (text report generation from images). To further demonstrate the drawback of language supervision, we show that features from RAD-DINO correlate with other medical records (e.g., sex or age) better than language-supervised models, which are generally not mentioned in radiology reports. Finally, we conduct a series of ablations determining the factors in RAD-DINO's performance; notably, we observe that RAD-DINO's downstream performance scales well with the quantity and diversity of training data, demonstrating that image-only supervision is a scalable approach for training a foundational biomedical image encoder.

  • 15 authors
·
Jan 19, 2024

Biomedical and Clinical Language Models for Spanish: On the Benefits of Domain-Specific Pretraining in a Mid-Resource Scenario

This work presents biomedical and clinical language models for Spanish by experimenting with different pretraining choices, such as masking at word and subword level, varying the vocabulary size and testing with domain data, looking for better language representations. Interestingly, in the absence of enough clinical data to train a model from scratch, we applied mixed-domain pretraining and cross-domain transfer approaches to generate a performant bio-clinical model suitable for real-world clinical data. We evaluated our models on Named Entity Recognition (NER) tasks for biomedical documents and challenging hospital discharge reports. When compared against the competitive mBERT and BETO models, we outperform them in all NER tasks by a significant margin. Finally, we studied the impact of the model's vocabulary on the NER performances by offering an interesting vocabulary-centric analysis. The results confirm that domain-specific pretraining is fundamental to achieving higher performances in downstream NER tasks, even within a mid-resource scenario. To the best of our knowledge, we provide the first biomedical and clinical transformer-based pretrained language models for Spanish, intending to boost native Spanish NLP applications in biomedicine. Our best models are freely available in the HuggingFace hub: https://huggingface.co/BSC-TeMU.

  • 7 authors
·
Sep 8, 2021

From Learning to Unlearning: Biomedical Security Protection in Multimodal Large Language Models

The security of biomedical Multimodal Large Language Models (MLLMs) has attracted increasing attention. However, training samples easily contain private information and incorrect knowledge that are difficult to detect, potentially leading to privacy leakage or erroneous outputs after deployment. An intuitive idea is to reprocess the training set to remove unwanted content and retrain the model from scratch. Yet, this is impractical due to significant computational costs, especially for large language models. Machine unlearning has emerged as a solution to this problem, which avoids complete retraining by selectively removing undesired knowledge derived from harmful samples while preserving required capabilities on normal cases. However, there exist no available datasets to evaluate the unlearning quality for security protection in biomedical MLLMs. To bridge this gap, we propose the first benchmark Multimodal Large Language Model Unlearning for BioMedicine (MLLMU-Med) built upon our novel data generation pipeline that effectively integrates synthetic private data and factual errors into the training set. Our benchmark targets two key scenarios: 1) Privacy protection, where patient private information is mistakenly included in the training set, causing models to unintentionally respond with private data during inference; and 2) Incorrectness removal, where wrong knowledge derived from unreliable sources is embedded into the dataset, leading to unsafe model responses. Moreover, we propose a novel Unlearning Efficiency Score that directly reflects the overall unlearning performance across different subsets. We evaluate five unlearning approaches on MLLMU-Med and find that these methods show limited effectiveness in removing harmful knowledge from biomedical MLLMs, indicating significant room for improvement. This work establishes a new pathway for further research in this promising field.

  • 5 authors
·
Aug 5, 2025

Large Language Models and Control Mechanisms Improve Text Readability of Biomedical Abstracts

Biomedical literature often uses complex language and inaccessible professional terminologies. That is why simplification plays an important role in improving public health literacy. Applying Natural Language Processing (NLP) models to automate such tasks allows for quick and direct accessibility for lay readers. In this work, we investigate the ability of state-of-the-art large language models (LLMs) on the task of biomedical abstract simplification, using the publicly available dataset for plain language adaptation of biomedical abstracts (PLABA). The methods applied include domain fine-tuning and prompt-based learning (PBL) on: 1) Encoder-decoder models (T5, SciFive, and BART), 2) Decoder-only GPT models (GPT-3.5 and GPT-4) from OpenAI and BioGPT, and 3) Control-token mechanisms on BART-based models. We used a range of automatic evaluation metrics, including BLEU, ROUGE, SARI, and BERTscore, and also conducted human evaluations. BART-Large with Control Token (BART-L-w-CT) mechanisms reported the highest SARI score of 46.54 and T5-base reported the highest BERTscore 72.62. In human evaluation, BART-L-w-CTs achieved a better simplicity score over T5-Base (2.9 vs. 2.2), while T5-Base achieved a better meaning preservation score over BART-L-w-CTs (3.1 vs. 2.6). We also categorised the system outputs with examples, hoping this will shed some light for future research on this task. Our code, fine-tuned models, and data splits are available at https://github.com/HECTA-UoM/PLABA-MU

  • 6 authors
·
Sep 22, 2023

Biomedical knowledge graph-optimized prompt generation for large language models

Large Language Models (LLMs) are being adopted at an unprecedented rate, yet still face challenges in knowledge-intensive domains like biomedicine. Solutions such as pre-training and domain-specific fine-tuning add substantial computational overhead, requiring further domain expertise. Here, we introduce a token-optimized and robust Knowledge Graph-based Retrieval Augmented Generation (KG-RAG) framework by leveraging a massive biomedical KG (SPOKE) with LLMs such as Llama-2-13b, GPT-3.5-Turbo and GPT-4, to generate meaningful biomedical text rooted in established knowledge. Compared to the existing RAG technique for Knowledge Graphs, the proposed method utilizes minimal graph schema for context extraction and uses embedding methods for context pruning. This optimization in context extraction results in more than 50% reduction in token consumption without compromising the accuracy, making a cost-effective and robust RAG implementation on proprietary LLMs. KG-RAG consistently enhanced the performance of LLMs across diverse biomedical prompts by generating responses rooted in established knowledge, accompanied by accurate provenance and statistical evidence (if available) to substantiate the claims. Further benchmarking on human curated datasets, such as biomedical true/false and multiple-choice questions (MCQ), showed a remarkable 71% boost in the performance of the Llama-2 model on the challenging MCQ dataset, demonstrating the framework's capacity to empower open-source models with fewer parameters for domain specific questions. Furthermore, KG-RAG enhanced the performance of proprietary GPT models, such as GPT-3.5 and GPT-4. In summary, the proposed framework combines explicit and implicit knowledge of KG and LLM in a token optimized fashion, thus enhancing the adaptability of general-purpose LLMs to tackle domain-specific questions in a cost-effective fashion.

  • 14 authors
·
Nov 28, 2023

Toward Reliable Biomedical Hypothesis Generation: Evaluating Truthfulness and Hallucination in Large Language Models

Large language models (LLMs) have shown significant potential in scientific disciplines such as biomedicine, particularly in hypothesis generation, where they can analyze vast literature, identify patterns, and suggest research directions. However, a key challenge lies in evaluating the truthfulness of generated hypotheses, as verifying their accuracy often requires substantial time and resources. Additionally, the hallucination problem in LLMs can lead to the generation of hypotheses that appear plausible but are ultimately incorrect, undermining their reliability. To facilitate the systematic study of these challenges, we introduce TruthHypo, a benchmark for assessing the capabilities of LLMs in generating truthful biomedical hypotheses, and KnowHD, a knowledge-based hallucination detector to evaluate how well hypotheses are grounded in existing knowledge. Our results show that LLMs struggle to generate truthful hypotheses. By analyzing hallucinations in reasoning steps, we demonstrate that the groundedness scores provided by KnowHD serve as an effective metric for filtering truthful hypotheses from the diverse outputs of LLMs. Human evaluations further validate the utility of KnowHD in identifying truthful hypotheses and accelerating scientific discovery. Our data and source code are available at https://github.com/Teddy-XiongGZ/TruthHypo.

  • 8 authors
·
May 20, 2025 2

Large Language Models as Biomedical Hypothesis Generators: A Comprehensive Evaluation

The rapid growth of biomedical knowledge has outpaced our ability to efficiently extract insights and generate novel hypotheses. Large language models (LLMs) have emerged as a promising tool to revolutionize knowledge interaction and potentially accelerate biomedical discovery. In this paper, we present a comprehensive evaluation of LLMs as biomedical hypothesis generators. We construct a dataset of background-hypothesis pairs from biomedical literature, carefully partitioned into training, seen, and unseen test sets based on publication date to mitigate data contamination. Using this dataset, we assess the hypothesis generation capabilities of top-tier instructed models in zero-shot, few-shot, and fine-tuning settings. To enhance the exploration of uncertainty, a crucial aspect of scientific discovery, we incorporate tool use and multi-agent interactions in our evaluation framework. Furthermore, we propose four novel metrics grounded in extensive literature review to evaluate the quality of generated hypotheses, considering both LLM-based and human assessments. Our experiments yield two key findings: 1) LLMs can generate novel and validated hypotheses, even when tested on literature unseen during training, and 2) Increasing uncertainty through multi-agent interactions and tool use can facilitate diverse candidate generation and improve zero-shot hypothesis generation performance. However, we also observe that the integration of additional knowledge through few-shot learning and tool use may not always lead to performance gains, highlighting the need for careful consideration of the type and scope of external knowledge incorporated. These findings underscore the potential of LLMs as powerful aids in biomedical hypothesis generation and provide valuable insights to guide further research in this area.

  • 9 authors
·
Jul 11, 2024

Bioformer: an efficient transformer language model for biomedical text mining

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.

  • 5 authors
·
Feb 3, 2023

Distilling Large Language Models for Biomedical Knowledge Extraction: A Case Study on Adverse Drug Events

Large language models (LLMs), such as GPT-4, have demonstrated remarkable capabilities across a wide range of tasks, including health applications. In this paper, we study how LLMs can be used to scale biomedical knowledge curation. We find that while LLMs already possess decent competency in structuring biomedical text, by distillation into a task-specific student model through self-supervised learning, substantial gains can be attained over out-of-box LLMs, with additional advantages such as cost, efficiency, and white-box model access. We conduct a case study on adverse drug event (ADE) extraction, which is an important area for improving care. On standard ADE extraction evaluation, a GPT-3.5 distilled PubMedBERT model attained comparable accuracy as supervised state-of-the-art models without using any labeled data. Despite being over 1,000 times smaller, the distilled model outperformed its teacher GPT-3.5 by over 6 absolute points in F1 and GPT-4 by over 5 absolute points. Ablation studies on distillation model choice (e.g., PubMedBERT vs BioGPT) and ADE extraction architecture shed light on best practice for biomedical knowledge extraction. Similar gains were attained by distillation for other standard biomedical knowledge extraction tasks such as gene-disease associations and protected health information, further illustrating the promise of this approach.

  • 11 authors
·
Jul 12, 2023 1

Assessing biomedical knowledge robustness in large language models by query-efficient sampling attacks

The increasing depth of parametric domain knowledge in large language models (LLMs) is fueling their rapid deployment in real-world applications. Understanding model vulnerabilities in high-stakes and knowledge-intensive tasks is essential for quantifying the trustworthiness of model predictions and regulating their use. The recent discovery of named entities as adversarial examples (i.e. adversarial entities) in natural language processing tasks raises questions about their potential impact on the knowledge robustness of pre-trained and finetuned LLMs in high-stakes and specialized domains. We examined the use of type-consistent entity substitution as a template for collecting adversarial entities for billion-parameter LLMs with biomedical knowledge. To this end, we developed an embedding-space attack based on powerscaled distance-weighted sampling to assess the robustness of their biomedical knowledge with a low query budget and controllable coverage. Our method has favorable query efficiency and scaling over alternative approaches based on random sampling and blackbox gradient-guided search, which we demonstrated for adversarial distractor generation in biomedical question answering. Subsequent failure mode analysis uncovered two regimes of adversarial entities on the attack surface with distinct characteristics and we showed that entity substitution attacks can manipulate token-wise Shapley value explanations, which become deceptive in this setting. Our approach complements standard evaluations for high-capacity models and the results highlight the brittleness of domain knowledge in LLMs.

  • 7 authors
·
Feb 16, 2024

BioTool: A Comprehensive Tool-Calling Dataset for Enhancing Biomedical Capabilities of Large Language Models

Despite the success of large language models (LLMs) on general-purpose tasks, their performance in highly specialized domains such as biomedicine remains unsatisfactory. A key limitation is the inability of LLMs to effectively leverage biomedical tools, which clinical experts and biomedical researchers rely on extensively in daily workflows. While recent general-domain tool-calling datasets have substantially improved the capabilities of LLM agents, existing efforts in the biomedical domain largely rely on in-context learning and restrict models to a small set of tools. To address this gap, we introduce BioTool, a comprehensive biomedical tool-calling dataset designed for fine-tuning LLMs. BioTool comprises 34 frequently used tools collected from the NCBI, Ensembl, and UniProt databases, along with 7,040 high-quality, human-verified query-API call pairs spanning variation, genomics, proteomics, evolution, and general biology. Fine-tuning a 4-billion-parameter LLM on BioTool yields substantial improvements in biomedical tool-calling performance, outperforming cutting-edge commercial LLMs such as GPT-5.1. Furthermore, human expert evaluations demonstrate that integrating a BioTool-fine-tuned tool caller significantly improves downstream answer quality compared to the same LLM without tool usage, highlighting the effectiveness of BioTool in enhancing the biomedical capabilities of LLMs. The full dataset and evaluation code are available at https://github.com/gxx27/BioTool

BIOMEDICA: An Open Biomedical Image-Caption Archive, Dataset, and Vision-Language Models Derived from Scientific Literature

The development of vision-language models (VLMs) is driven by large-scale and diverse multimodal datasets. However, progress toward generalist biomedical VLMs is limited by the lack of annotated, publicly accessible datasets across biology and medicine. Existing efforts are restricted to narrow domains, missing the full diversity of biomedical knowledge encoded in scientific literature. To address this gap, we introduce BIOMEDICA, a scalable, open-source framework to extract, annotate, and serialize the entirety of the PubMed Central Open Access subset into an easy-to-use, publicly accessible dataset.Our framework produces a comprehensive archive with over 24 million unique image-text pairs from over 6 million articles. Metadata and expert-guided annotations are also provided. We demonstrate the utility and accessibility of our resource by releasing BMCA-CLIP, a suite of CLIP-style models continuously pre-trained on the BIOMEDICA dataset via streaming, eliminating the need to download 27 TB of data locally.On average, our models achieve state-of-the-art performance across 40 tasks - spanning pathology, radiology, ophthalmology, dermatology, surgery, molecular biology, parasitology, and cell biology - excelling in zero-shot classification with a 6.56% average improvement (as high as 29.8% and 17.5% in dermatology and ophthalmology, respectively), and stronger image-text retrieval, all while using 10x less compute. To foster reproducibility and collaboration, we release our codebase and dataset for the broader research community.

  • 16 authors
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Jan 13, 2025 3

Med-V1: Small Language Models for Zero-shot and Scalable Biomedical Evidence Attribution

Assessing whether an article supports an assertion is essential for hallucination detection and claim verification. While large language models (LLMs) have the potential to automate this task, achieving strong performance requires frontier models such as GPT-5 that are prohibitively expensive to deploy at scale. To efficiently perform biomedical evidence attribution, we present Med-V1, a family of small language models with only three billion parameters. Trained on high-quality synthetic data newly developed in this study, Med-V1 substantially outperforms (+27.0% to +71.3%) its base models on five biomedical benchmarks unified into a verification format. Despite its smaller size, Med-V1 performs comparably to frontier LLMs such as GPT-5, along with high-quality explanations for its predictions. We use Med-V1 to conduct a first-of-its-kind use case study that quantifies hallucinations in LLM-generated answers under different citation instructions. Results show that the format instruction strongly affects citation validity and hallucination, with GPT-5 generating more claims but exhibiting hallucination rates similar to GPT-4o. Additionally, we present a second use case showing that Med-V1 can automatically identify high-stakes evidence misattributions in clinical practice guidelines, revealing potentially negative public health impacts that are otherwise challenging to identify at scale. Overall, Med-V1 provides an efficient and accurate lightweight alternative to frontier LLMs for practical and real-world applications in biomedical evidence attribution and verification tasks. Med-V1 is available at https://github.com/ncbi-nlp/Med-V1.

  • 15 authors
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Mar 5

GeneGPT: Augmenting Large Language Models with Domain Tools for Improved Access to Biomedical Information

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.

  • 4 authors
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Apr 19, 2023

HILGEN: Hierarchically-Informed Data Generation for Biomedical NER Using Knowledgebases and Large Language Models

We present HILGEN, a Hierarchically-Informed Data Generation approach that combines domain knowledge from the Unified Medical Language System (UMLS) with synthetic data generated by large language models (LLMs), specifically GPT-3.5. Our approach leverages UMLS's hierarchical structure to expand training data with related concepts, while incorporating contextual information from LLMs through targeted prompts aimed at automatically generating synthetic examples for sparsely occurring named entities. The performance of the HILGEN approach was evaluated across four biomedical NER datasets (MIMIC III, BC5CDR, NCBI-Disease, and Med-Mentions) using BERT-Large and DANN (Data Augmentation with Nearest Neighbor Classifier) models, applying various data generation strategies, including UMLS, GPT-3.5, and their best ensemble. For the BERT-Large model, incorporating UMLS led to an average F1 score improvement of 40.36%, while using GPT-3.5 resulted in a comparable average increase of 40.52%. The Best-Ensemble approach using BERT-Large achieved the highest improvement, with an average increase of 42.29%. DANN model's F1 score improved by 22.74% on average using the UMLS-only approach. The GPT-3.5-based method resulted in a 21.53% increase, and the Best-Ensemble DANN model showed a more notable improvement, with an average increase of 25.03%. Our proposed HILGEN approach improves NER performance in few-shot settings without requiring additional manually annotated data. Our experiments demonstrate that an effective strategy for optimizing biomedical NER is to combine biomedical knowledge curated in the past, such as the UMLS, and generative LLMs to create synthetic training instances. Our future research will focus on exploring additional innovative synthetic data generation strategies for further improving NER performance.

  • 6 authors
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Mar 6, 2025

Interpretable Bilingual Multimodal Large Language Model for Diverse Biomedical Tasks

Several medical Multimodal Large Languange Models (MLLMs) have been developed to address tasks involving visual images with textual instructions across various medical modalities, achieving impressive results. Most current medical generalist models are region-agnostic, treating the entire image as a holistic representation. However, they struggle to identify which specific regions they are focusing on when generating a sentence. To mimic the behavior of doctors, who typically begin by reviewing the entire image before concentrating on specific regions for a thorough evaluation, we aim to enhance the capability of medical MLLMs in understanding anatomical regions within entire medical scans. To achieve it, we first formulate Region-Centric tasks and construct a large-scale dataset, MedRegInstruct, to incorporate regional information into training. Combining our collected dataset with other medical multimodal corpora for training, we propose a Region-Aware medical MLLM, MedRegA, which is the first bilingual generalist medical AI system to simultaneously handle image-level and region-level medical vision-language tasks across a broad range of modalities. Our MedRegA not only enables three region-centric tasks, but also achieves the best performance for visual question answering, report generation and medical image classification over 8 modalities, showcasing significant versatility. Experiments demonstrate that our model can not only accomplish powerful performance across various medical vision-language tasks in bilingual settings, but also recognize and detect structures in multimodal medical scans, boosting the interpretability and user interactivity of medical MLLMs. Our project page is https://medrega.github.io.

  • 7 authors
·
Oct 23, 2024

Biomedical Large Languages Models Seem not to be Superior to Generalist Models on Unseen Medical Data

Large language models (LLMs) have shown potential in biomedical applications, leading to efforts to fine-tune them on domain-specific data. However, the effectiveness of this approach remains unclear. This study evaluates the performance of biomedically fine-tuned LLMs against their general-purpose counterparts on a variety of clinical tasks. We evaluated their performance on clinical case challenges from the New England Journal of Medicine (NEJM) and the Journal of the American Medical Association (JAMA) and on several clinical tasks (e.g., information extraction, document summarization, and clinical coding). Using benchmarks specifically chosen to be likely outside the fine-tuning datasets of biomedical models, we found that biomedical LLMs mostly perform inferior to their general-purpose counterparts, especially on tasks not focused on medical knowledge. While larger models showed similar performance on case tasks (e.g., OpenBioLLM-70B: 66.4% vs. Llama-3-70B-Instruct: 65% on JAMA cases), smaller biomedical models showed more pronounced underperformance (e.g., OpenBioLLM-8B: 30% vs. Llama-3-8B-Instruct: 64.3% on NEJM cases). Similar trends were observed across the CLUE (Clinical Language Understanding Evaluation) benchmark tasks, with general-purpose models often performing better on text generation, question answering, and coding tasks. Our results suggest that fine-tuning LLMs to biomedical data may not provide the expected benefits and may potentially lead to reduced performance, challenging prevailing assumptions about domain-specific adaptation of LLMs and highlighting the need for more rigorous evaluation frameworks in healthcare AI. Alternative approaches, such as retrieval-augmented generation, may be more effective in enhancing the biomedical capabilities of LLMs without compromising their general knowledge.

  • 11 authors
·
Aug 25, 2024

DAEDRA: A language model for predicting outcomes in passive pharmacovigilance reporting

Over the recent years, the emergence of large language models (LLMs) has given rise to a proliferation of domain-specific models that are intended to reflect the particularities of linguistic context and content as a correlate of the originating domain. This paper details the conception, design, training and evaluation of DAEDRA, a LLM designed to detect regulatory-relevant outcomes (mortality, ER attendance and hospitalisation) in adverse event reports elicited through passive reporting (PR). While PR is a highly cost-efficient way of eliciting information from a wide and diverse audience -- typically including not only physicians and healthcare providers but also patients, family members and other lay stakeholders --, this diversity makes PR corpora difficult to analyse. Generic language models may not capture the complex clinical dimensions while specific clinical or biomedical models may not perform well on lay reports. To evaluate the utility of a subdomain-specific language model, an adaptive training approach was adapted, wherein base language model candidates were evaluated on a subset of the corpus, and the best performer was trained on the entire corpus. This yielded a small but significant improvement in F_1 (+1%), precision (+2.5%) and recall (+3.8%), at a relatively low training cost and a single-day training time. Subdomain-specific LLMs continue to be viable options for better results when analysing highly specialised corpora.

  • 1 authors
·
Feb 10, 2024

MicroVQA++: High-Quality Microscopy Reasoning Dataset with Weakly Supervised Graphs for Multimodal Large Language Model

Multimodal Large Language Models are increasingly applied to biomedical imaging, yet scientific reasoning for microscopy remains limited by the scarcity of large-scale, high-quality training data. We introduce MicroVQA++, a three-stage, large-scale and high-quality microscopy VQA corpus derived from the BIOMEDICA archive. Stage one bootstraps supervision from expert-validated figure-caption pairs sourced from peer-reviewed articles. Stage two applies HiCQA-Graph, a novel heterogeneous graph over images, captions, and QAs that fuses NLI-based textual entailment, CLIP-based vision-language alignment, and agent signals to identify and filter inconsistent samples. Stage three uses a MultiModal Large Language Model (MLLM) agent to generate multiple-choice questions (MCQ) followed by human screening. The resulting release comprises a large training split and a human-checked test split whose Bloom's level hard-sample distribution exceeds the MicroVQA benchmark. Our work delivers (i) a quality-controlled dataset that couples expert literature with graph-based filtering and human refinement; (ii) HiCQA-Graph, the first graph that jointly models (image, caption, QA) for cross-modal consistency filtering; (iii) evidence that careful data construction enables 4B-scale MLLMs to reach competitive microscopy reasoning performance (e.g., GPT-5) and achieve state-of-the-art performance among open-source MLLMs. Code and dataset will be released after the review process concludes.

  • 5 authors
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Nov 14, 2025 2

Large language models in healthcare and medical domain: A review

The deployment of large language models (LLMs) within the healthcare sector has sparked both enthusiasm and apprehension. These models exhibit the remarkable capability to provide proficient responses to free-text queries, demonstrating a nuanced understanding of professional medical knowledge. This comprehensive survey delves into the functionalities of existing LLMs designed for healthcare applications, elucidating the trajectory of their development, starting from traditional Pretrained Language Models (PLMs) to the present state of LLMs in healthcare sector. First, we explore the potential of LLMs to amplify the efficiency and effectiveness of diverse healthcare applications, particularly focusing on clinical language understanding tasks. These tasks encompass a wide spectrum, ranging from named entity recognition and relation extraction to natural language inference, multi-modal medical applications, document classification, and question-answering. Additionally, we conduct an extensive comparison of the most recent state-of-the-art LLMs in the healthcare domain, while also assessing the utilization of various open-source LLMs and highlighting their significance in healthcare applications. Furthermore, we present the essential performance metrics employed to evaluate LLMs in the biomedical domain, shedding light on their effectiveness and limitations. Finally, we summarize the prominent challenges and constraints faced by large language models in the healthcare sector, offering a holistic perspective on their potential benefits and shortcomings. This review provides a comprehensive exploration of the current landscape of LLMs in healthcare, addressing their role in transforming medical applications and the areas that warrant further research and development.

  • 2 authors
·
Dec 12, 2023

Unifying Segment Anything in Microscopy with Multimodal Large Language Model

Accurate segmentation of regions of interest in biomedical images holds substantial value in image analysis. Although several foundation models for biomedical segmentation have currently achieved excellent performance on certain datasets, they typically demonstrate sub-optimal performance on unseen domain data. We owe the deficiency to lack of vision-language knowledge before segmentation. Multimodal Large Language Models (MLLMs) bring outstanding understanding and reasoning capabilities to multimodal tasks, which inspires us to leverage MLLMs to inject Vision-Language Knowledge (VLK), thereby enabling vision models to demonstrate superior generalization capabilities on cross-domain datasets. In this paper, we propose using MLLMs to guide SAM in learning microscopy crose-domain data, unifying Segment Anything in Microscopy, named uLLSAM. Specifically, we propose the Vision-Language Semantic Alignment (VLSA) module, which injects VLK into Segment Anything Model (SAM). We find that after SAM receives global VLK prompts, its performance improves significantly, but there are deficiencies in boundary contour perception. Therefore, we further propose Semantic Boundary Regularization (SBR) to prompt SAM. Our method achieves performance improvements of 7.71% in Dice and 12.10% in SA across 9 in-domain microscopy datasets, achieving state-of-the-art performance. Our method also demonstrates improvements of 6.79% in Dice and 10.08% in SA across 10 out-ofdomain datasets, exhibiting strong generalization capabilities. Code is available at https://github.com/ieellee/uLLSAM.

  • 5 authors
·
May 15, 2025 2

Towards a Multimodal Large Language Model with Pixel-Level Insight for Biomedicine

In recent years, Multimodal Large Language Models (MLLM) have achieved notable advancements, demonstrating the feasibility of developing an intelligent biomedical assistant. However, current biomedical MLLMs predominantly focus on image-level understanding and restrict interactions to textual commands, thus limiting their capability boundaries and the flexibility of usage. In this paper, we introduce a novel end-to-end multimodal large language model for the biomedical domain, named MedPLIB, which possesses pixel-level understanding. Excitingly, it supports visual question answering (VQA), arbitrary pixel-level prompts (points, bounding boxes, and free-form shapes), and pixel-level grounding. We propose a novel Mixture-of-Experts (MoE) multi-stage training strategy, which divides MoE into separate training phases for a visual-language expert model and a pixel-grounding expert model, followed by fine-tuning using MoE. This strategy effectively coordinates multitask learning while maintaining the computational cost at inference equivalent to that of a single expert model. To advance the research of biomedical MLLMs, we introduce the Medical Complex Vision Question Answering Dataset (MeCoVQA), which comprises an array of 8 modalities for complex medical imaging question answering and image region understanding. Experimental results indicate that MedPLIB has achieved state-of-the-art outcomes across multiple medical visual language tasks. More importantly, in zero-shot evaluations for the pixel grounding task, MedPLIB leads the best small and large models by margins of 19.7 and 15.6 respectively on the mDice metric. The codes, data, and model checkpoints will be made publicly available at https://github.com/ShawnHuang497/MedPLIB.

  • 7 authors
·
Dec 12, 2024

Large Language Models Meet Text-Attributed Graphs: A Survey of Integration Frameworks and Applications

Large Language Models (LLMs) have achieved remarkable success in natural language processing through strong semantic understanding and generation. However, their black-box nature limits structured and multi-hop reasoning. In contrast, Text-Attributed Graphs (TAGs) provide explicit relational structures enriched with textual context, yet often lack semantic depth. Recent research shows that combining LLMs and TAGs yields complementary benefits: enhancing TAG representation learning and improving the reasoning and interpretability of LLMs. This survey provides the first systematic review of LLM--TAG integration from an orchestration perspective. We introduce a novel taxonomy covering two fundamental directions: LLM for TAG, where LLMs enrich graph-based tasks, and TAG for LLM, where structured graphs improve LLM reasoning. We categorize orchestration strategies into sequential, parallel, and multi-module frameworks, and discuss advances in TAG-specific pretraining, prompting, and parameter-efficient fine-tuning. Beyond methodology, we summarize empirical insights, curate available datasets, and highlight diverse applications across recommendation systems, biomedical analysis, and knowledge-intensive question answering. Finally, we outline open challenges and promising research directions, aiming to guide future work at the intersection of language and graph learning.

  • 6 authors
·
Oct 23, 2025

Not All Large Language Models (LLMs) Succumb to the "Reversal Curse": A Comparative Study of Deductive Logical Reasoning in BERT and GPT Models

The "Reversal Curse" refers to the scenario where auto-regressive decoder large language models (LLMs), such as ChatGPT, trained on "A is B" fail to learn "B is A", demonstrating a basic failure of logical deduction. This raises a red flag in the use of GPT models for certain general tasks such as constructing knowledge graphs, considering their adherence to this symmetric principle. In our study, we examined a bidirectional LLM, BERT, and found that it is immune to the reversal curse. Driven by ongoing efforts to construct biomedical knowledge graphs with LLMs, we also embarked on evaluating more complex but essential deductive reasoning capabilities. This process included first training encoder and decoder language models to master the intersection (cap) and union (cup) operations on two sets and then moving on to assess their capability to infer different combinations of union (cup) and intersection (cap) operations on three newly created sets. The findings showed that while both encoder and decoder language models, trained for tasks involving two sets (union/intersection), were proficient in such scenarios, they encountered difficulties when dealing with operations that included three sets (various combinations of union and intersection). Our research highlights the distinct characteristics of encoder and decoder models in simple and complex logical reasoning. In practice, the choice between BERT and GPT should be guided by the specific requirements and nature of the task at hand, leveraging their respective strengths in bidirectional context comprehension and sequence prediction.

  • 3 authors
·
Dec 6, 2023

GP-GPT: Large Language Model for Gene-Phenotype Mapping

Pre-trained large language models(LLMs) have attracted increasing attention in biomedical domains due to their success in natural language processing. However, the complex traits and heterogeneity of multi-sources genomics data pose significant challenges when adapting these models to the bioinformatics and biomedical field. To address these challenges, we present GP-GPT, the first specialized large language model for genetic-phenotype knowledge representation and genomics relation analysis. Our model is fine-tuned in two stages on a comprehensive corpus composed of over 3,000,000 terms in genomics, proteomics, and medical genetics, derived from multiple large-scale validated datasets and scientific publications. GP-GPT demonstrates proficiency in accurately retrieving medical genetics information and performing common genomics analysis tasks, such as genomics information retrieval and relationship determination. Comparative experiments across domain-specific tasks reveal that GP-GPT outperforms state-of-the-art LLMs, including Llama2, Llama3 and GPT-4. These results highlight GP-GPT's potential to enhance genetic disease relation research and facilitate accurate and efficient analysis in the fields of genomics and medical genetics. Our investigation demonstrated the subtle changes of bio-factor entities' representations in the GP-GPT, which suggested the opportunities for the application of LLMs to advancing gene-phenotype research.

  • 18 authors
·
Sep 15, 2024

UniBiomed: A Universal Foundation Model for Grounded Biomedical Image Interpretation

Multi-modal interpretation of biomedical images opens up novel opportunities in biomedical image analysis. Conventional AI approaches typically rely on disjointed training, i.e., Large Language Models (LLMs) for clinical text generation and segmentation models for target extraction, which results in inflexible real-world deployment and a failure to leverage holistic biomedical information. To this end, we introduce UniBiomed, the first universal foundation model for grounded biomedical image interpretation. UniBiomed is based on a novel integration of Multi-modal Large Language Model (MLLM) and Segment Anything Model (SAM), which effectively unifies the generation of clinical texts and the segmentation of corresponding biomedical objects for grounded interpretation. In this way, UniBiomed is capable of tackling a wide range of biomedical tasks across ten diverse biomedical imaging modalities. To develop UniBiomed, we curate a large-scale dataset comprising over 27 million triplets of images, annotations, and text descriptions across ten imaging modalities. Extensive validation on 84 internal and external datasets demonstrated that UniBiomed achieves state-of-the-art performance in segmentation, disease recognition, region-aware diagnosis, visual question answering, and report generation. Moreover, unlike previous models that rely on clinical experts to pre-diagnose images and manually craft precise textual or visual prompts, UniBiomed can provide automated and end-to-end grounded interpretation for biomedical image analysis. This represents a novel paradigm shift in clinical workflows, which will significantly improve diagnostic efficiency. In summary, UniBiomed represents a novel breakthrough in biomedical AI, unlocking powerful grounded interpretation capabilities for more accurate and efficient biomedical image analysis.

  • 5 authors
·
Apr 30, 2025 4

A Japanese Language Model and Three New Evaluation Benchmarks for Pharmaceutical NLP

We present a Japanese domain-specific language model for the pharmaceutical field, developed through continual pretraining on 2 billion Japanese pharmaceutical tokens and 8 billion English biomedical tokens. To enable rigorous evaluation, we introduce three new benchmarks: YakugakuQA, based on national pharmacist licensing exams; NayoseQA, which tests cross-lingual synonym and terminology normalization; and SogoCheck, a novel task designed to assess consistency reasoning between paired statements. We evaluate our model against both open-source medical LLMs and commercial models, including GPT-4o. Results show that our domain-specific model outperforms existing open models and achieves competitive performance with commercial ones, particularly on terminology-heavy and knowledge-based tasks. Interestingly, even GPT-4o performs poorly on SogoCheck, suggesting that cross-sentence consistency reasoning remains an open challenge. Our benchmark suite offers a broader diagnostic lens for pharmaceutical NLP, covering factual recall, lexical variation, and logical consistency. This work demonstrates the feasibility of building practical, secure, and cost-effective language models for Japanese domain-specific applications, and provides reusable evaluation resources for future research in pharmaceutical and healthcare NLP. Our model, codes, and datasets are released at https://github.com/EQUES-Inc/pharma-LLM-eval.

  • 5 authors
·
May 22, 2025

PlantBert: An Open Source Language Model for Plant Science

The rapid advancement of transformer-based language models has catalyzed breakthroughs in biomedical and clinical natural language processing; however, plant science remains markedly underserved by such domain-adapted tools. In this work, we present PlantBert, a high-performance, open-source language model specifically tailored for extracting structured knowledge from plant stress-response literature. Built upon the DeBERTa architecture-known for its disentangled attention and robust contextual encoding-PlantBert is fine-tuned on a meticulously curated corpus of expert-annotated abstracts, with a primary focus on lentil (Lens culinaris) responses to diverse abiotic and biotic stressors. Our methodology combines transformer-based modeling with rule-enhanced linguistic post-processing and ontology-grounded entity normalization, enabling PlantBert to capture biologically meaningful relationships with precision and semantic fidelity. The underlying corpus is annotated using a hierarchical schema aligned with the Crop Ontology, encompassing molecular, physiological, biochemical, and agronomic dimensions of plant adaptation. PlantBert exhibits strong generalization capabilities across entity types and demonstrates the feasibility of robust domain adaptation in low-resource scientific fields. By providing a scalable and reproducible framework for high-resolution entity recognition, PlantBert bridges a critical gap in agricultural NLP and paves the way for intelligent, data-driven systems in plant genomics, phenomics, and agronomic knowledge discovery. Our model is publicly released to promote transparency and accelerate cross-disciplinary innovation in computational plant science.

  • 8 authors
·
Jun 10, 2025

Self-Specialization: Uncovering Latent Expertise within Large Language Models

Recent works have demonstrated the effectiveness of self-alignment in which a large language model is, by itself, aligned to follow general instructions through the automatic generation of instructional data using a handful of human-written seeds. Instead of general alignment, in this work, we focus on self-alignment for expert domain specialization (e.g., biomedicine), discovering it to be very effective for improving zero-shot and few-shot performance in target domains of interest. As a preliminary, we first present the benchmark results of existing aligned models within a specialized domain, which reveals the marginal effect that "generic" instruction-following training has on downstream expert domains' performance. To remedy this, we explore self-specialization that leverages domain-specific unlabelled data and a few labeled seeds for the self-alignment process. When augmented with retrieval to reduce hallucination and enhance concurrency of the alignment, self-specialization offers an effective (and efficient) way of "carving out" an expert model out of a "generalist", pre-trained LLM where different domains of expertise are originally combined in a form of "superposition". Our experimental results on a biomedical domain show that our self-specialized model (30B) outperforms its base model, MPT-30B by a large margin and even surpasses larger popular models based on LLaMA-65B, highlighting its potential and practicality for specialization, especially considering its efficiency in terms of data and parameters.

  • 8 authors
·
Sep 29, 2023

Automatic Calibration and Error Correction for Large Language Models via Pareto Optimal Self-Supervision

Large language models (LLMs) have demonstrated remarkable capabilities out of box for a wide range of applications, yet accuracy still remains a major growth area, especially in mission-critical domains such as biomedicine. An effective method to calibrate the confidence level on LLM responses is essential to automatically detect errors and facilitate human-in-the-loop verification. An important source of calibration signals stems from expert-stipulated programmatic supervision, which is often available at low cost but has its own limitations such as noise and coverage. In this paper, we introduce a Pareto optimal self-supervision framework that can leverage available programmatic supervision to systematically calibrate LLM responses by producing a risk score for every response, without any additional manual efforts. This is accomplished by learning a harmonizer model to align LLM output with other available supervision sources, which would assign higher risk scores to more uncertain LLM responses and facilitate error correction. Experiments on standard relation extraction tasks in biomedical and general domains demonstrate the promise of this approach, with our proposed risk scores highly correlated with the real error rate of LLMs. For the most uncertain test instances, dynamic prompting based on our proposed risk scores results in significant accuracy improvement for off-the-shelf LLMs, boosting GPT-3 results past state-of-the-art (SOTA) weak supervision and GPT-4 results past SOTA supervised results on challenging evaluation datasets.

  • 4 authors
·
Jun 28, 2023 1

Me LLaMA: Foundation Large Language Models for Medical Applications

Recent large language models (LLMs) such as ChatGPT and LLaMA have shown great promise in many AI applications. However, their performance on medical tasks is suboptimal and can be improved by training on extensive domain-specific datasets. This study introduces Me LLaMA, a medical LLM family that includes foundation models - Me LLaMA 13/70B, along with their chat-enhanced versions - Me LLaMA 13/70B-chat, developed through continual pre-training and instruction tuning of LLaMA2 using large medical datasets. Our domain-specific data suite for training and evaluation includes a large-scale, continual pre-training dataset with 129B tokens, an instruction tuning dataset with 214k samples, and a new medical evaluation benchmark (MIBE) across six tasks with 12 datasets. Our extensive evaluation using the MIBE shows that Me LLaMA models achieve overall better performance than existing open-source medical LLMs in zero-shot, few-shot and supervised learning abilities. Their zero-shot performance is comparable with ChatGPT across 7 out of 8 datasets, with a slight variance of within 3%, and yet falls short when compared to GPT-4. In addition, we investigated the catastrophic forgetting problem, and our results show that Me LLaMA models outperform other open-source medical LLMs in mitigating this issue. Me LLaMA is one of the largest open-source medical foundation LLMs that use both biomedical and clinical data. It exhibits superior performance across both general and medical tasks compared to other open-source medical LLMs, rendering it an attractive choice for medical AI applications. We release our models, datasets, and evaluation scripts at: https://github.com/BIDS-Xu-Lab/Me-LLaMA.

  • 16 authors
·
Feb 20, 2024

Can Open-Source LLMs Compete with Commercial Models? Exploring the Few-Shot Performance of Current GPT Models in Biomedical Tasks

Commercial large language models (LLMs), like OpenAI's GPT-4 powering ChatGPT and Anthropic's Claude 3 Opus, have dominated natural language processing (NLP) benchmarks across different domains. New competing Open-Source alternatives like Mixtral 8x7B or Llama 3 have emerged and seem to be closing the gap while often offering higher throughput and being less costly to use. Open-Source LLMs can also be self-hosted, which makes them interesting for enterprise and clinical use cases where sensitive data should not be processed by third parties. We participated in the 12th BioASQ challenge, which is a retrieval augmented generation (RAG) setting, and explored the performance of current GPT models Claude 3 Opus, GPT-3.5-turbo and Mixtral 8x7b with in-context learning (zero-shot, few-shot) and QLoRa fine-tuning. We also explored how additional relevant knowledge from Wikipedia added to the context-window of the LLM might improve their performance. Mixtral 8x7b was competitive in the 10-shot setting, both with and without fine-tuning, but failed to produce usable results in the zero-shot setting. QLoRa fine-tuning and Wikipedia context did not lead to measurable performance gains. Our results indicate that the performance gap between commercial and open-source models in RAG setups exists mainly in the zero-shot setting and can be closed by simply collecting few-shot examples for domain-specific use cases. The code needed to rerun these experiments is available through GitHub.

  • 2 authors
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Jul 18, 2024

GLiNER-biomed: A Suite of Efficient Models for Open Biomedical Named Entity Recognition

Biomedical named entity recognition (NER) presents unique challenges due to specialized vocabularies, the sheer volume of entities, and the continuous emergence of novel entities. Traditional NER models, constrained by fixed taxonomies and human annotations, struggle to generalize beyond predefined entity types or efficiently adapt to emerging concepts. To address these issues, we introduce GLiNER-biomed, a domain-adapted suite of Generalist and Lightweight Model for NER (GLiNER) models specifically tailored for biomedical NER. In contrast to conventional approaches, GLiNER uses natural language descriptions to infer arbitrary entity types, enabling zero-shot recognition. Our approach first distills the annotation capabilities of large language models (LLMs) into a smaller, more efficient model, enabling the generation of high-coverage synthetic biomedical NER data. We subsequently train two GLiNER architectures, uni- and bi-encoder, at multiple scales to balance computational efficiency and recognition performance. Evaluations on several biomedical datasets demonstrate that GLiNER-biomed outperforms state-of-the-art GLiNER models in both zero- and few-shot scenarios, achieving 5.96% improvement in F1-score over the strongest baseline. Ablation studies highlight the effectiveness of our synthetic data generation strategy and emphasize the complementary benefits of synthetic biomedical pre-training combined with fine-tuning on high-quality general-domain annotations. All datasets, models, and training pipelines are publicly available at https://github.com/ds4dh/GLiNER-biomed.

  • 3 authors
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Apr 1, 2025

A general language model for peptide identification

Advances in peptide identification are revolutionizing our ability to decipher protein functions and accelerate therapeutic discovery. We present PDeepPP, a deep learning framework that integrates pretrained protein language models with parallel transformer-CNN architectures, achieving state-of-the-art performance in peptide characterization tasks. The model's hybrid architecture demonstrates unique capabilities in capturing both local sequence motifs and global structural features, as evidenced by 29% improved cluster separation in UMAP visualizations compared to conventional approaches. Evaluated across 33 biological recognition tasks - including post-translational modification site prediction and bioactive peptide identification - PDeepPP outperformed existing methods in 25 tasks with average AUC improvements of 4.2%. Notably, it achieved 0.9726 accuracy with PR AUC 0.9977 in antimicrobial peptide detection while reducing false negatives by 37.5% in antimalarial recognition scenarios. This framework enables accurate large-scale peptide analysis, achieving 218* acceleration over sequence-alignment-based methods while maintaining 99.5% specificity in critical glycosylation site detection.PDeepPP establishes a new paradigm for computational peptide analysis through its synergistic architecture design, enabling rapid yet precise functional annotation that bridges molecular pattern recognition with translational biomedical applications.We have made our implementation, including code, data, and pretrained models, publicly available via GitHub (https://github.com/fondress/PDeepPP) and Hugging Face (https://huggingface.co/fondress/PDeppPP).

  • 8 authors
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Feb 21, 2025

MedKGent: A Large Language Model Agent Framework for Constructing Temporally Evolving Medical Knowledge Graph

The rapid expansion of medical literature presents growing challenges for structuring and integrating domain knowledge at scale. Knowledge Graphs (KGs) offer a promising solution by enabling efficient retrieval, automated reasoning, and knowledge discovery. However, current KG construction methods often rely on supervised pipelines with limited generalizability or naively aggregate outputs from Large Language Models (LLMs), treating biomedical corpora as static and ignoring the temporal dynamics and contextual uncertainty of evolving knowledge. To address these limitations, we introduce MedKGent, a LLM agent framework for constructing temporally evolving medical KGs. Leveraging over 10 million PubMed abstracts published between 1975 and 2023, we simulate the emergence of biomedical knowledge via a fine-grained daily time series. MedKGent incrementally builds the KG in a day-by-day manner using two specialized agents powered by the Qwen2.5-32B-Instruct model. The Extractor Agent identifies knowledge triples and assigns confidence scores via sampling-based estimation, which are used to filter low-confidence extractions and inform downstream processing. The Constructor Agent incrementally integrates the retained triples into a temporally evolving graph, guided by confidence scores and timestamps to reinforce recurring knowledge and resolve conflicts. The resulting KG contains 156,275 entities and 2,971,384 relational triples. Quality assessments by two SOTA LLMs and three domain experts demonstrate an accuracy approaching 90%, with strong inter-rater agreement. To evaluate downstream utility, we conduct RAG across seven medical question answering benchmarks using five leading LLMs, consistently observing significant improvements over non-augmented baselines. Case studies further demonstrate the KG's value in literature-based drug repurposing via confidence-aware causal inference.

  • 13 authors
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Aug 17, 2025

Dragonfly: Multi-Resolution Zoom Supercharges Large Visual-Language Model

Recent advances in large multimodal models (LMMs) suggest that higher image resolution enhances the fine-grained understanding of image details, crucial for tasks such as visual commonsense reasoning and analyzing biomedical images. However, increasing input resolution poses two main challenges: 1) It extends the context length required by the language model, leading to inefficiencies and hitting the model's context limit; 2) It increases the complexity of visual features, necessitating more training data or more complex architecture. We introduce Dragonfly, a new LMM architecture that enhances fine-grained visual understanding and reasoning about image regions to address these challenges. Dragonfly employs two key strategies: multi-resolution visual encoding and zoom-in patch selection. These strategies allow the model to process high-resolution images efficiently while maintaining reasonable context length. Our experiments on eight popular benchmarks demonstrate that Dragonfly achieves competitive or better performance compared to other architectures, highlighting the effectiveness of our design. Additionally, we finetuned Dragonfly on biomedical instructions, achieving state-of-the-art results on multiple biomedical tasks requiring fine-grained visual understanding, including 92.3% accuracy on the Path-VQA dataset (compared to 83.3% for Med-Gemini) and the highest reported results on biomedical image captioning. To support model training, we curated a visual instruction-tuning dataset with 5.5 million image-instruction samples in the general domain and 1.4 million samples in the biomedical domain. We also conducted ablation studies to characterize the impact of various architectural designs and image resolutions, providing insights for future research on visual instruction alignment. The codebase and model are available at https://github.com/togethercomputer/Dragonfly.

  • 6 authors
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Jun 3, 2024

ChroKnowledge: Unveiling Chronological Knowledge of Language Models in Multiple Domains

Large language models (LLMs) have significantly impacted many aspects of our lives. However, assessing and ensuring their chronological knowledge remains challenging. Existing approaches fall short in addressing the accumulative nature of knowledge, often relying on a single time stamp. To overcome this, we introduce ChroKnowBench, a benchmark dataset designed to evaluate chronologically accumulated knowledge across three key aspects: multiple domains, time dependency, temporal state. Our benchmark distinguishes between knowledge that evolves (e.g., scientific discoveries, amended laws) and knowledge that remain constant (e.g., mathematical truths, commonsense facts). Building on this benchmark, we present ChroKnowledge (Chronological Categorization of Knowledge), a novel sampling-based framework for evaluating and updating LLMs' non-parametric chronological knowledge. Our evaluation shows: (1) The ability of eliciting temporal knowledge varies depending on the data format that model was trained on. (2) LLMs partially recall knowledge or show a cut-off at temporal boundaries rather than recalling all aspects of knowledge correctly. Thus, we apply our ChroKnowPrompt, an in-depth prompting to elicit chronological knowledge by traversing step-by-step through the surrounding time spans. We observe that our framework successfully updates the overall knowledge across the entire timeline in both the biomedical domain (+11.9%) and the general domain (+2.8%), demonstrating its effectiveness in refining temporal knowledge. This non-parametric approach also enables knowledge updates not only in open-source models but also in proprietary LLMs, ensuring comprehensive applicability across model types. We perform a comprehensive analysis based on temporal characteristics of ChroKnowPrompt and validate the potential of various models to elicit intrinsic temporal knowledge through our method.

  • 6 authors
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Oct 13, 2024 3

Improving Medical Reasoning through Retrieval and Self-Reflection with Retrieval-Augmented Large Language Models

Recent proprietary large language models (LLMs), such as GPT-4, have achieved a milestone in tackling diverse challenges in the biomedical domain, ranging from multiple-choice questions to long-form generations. To address challenges that still cannot be handled with the encoded knowledge of LLMs, various retrieval-augmented generation (RAG) methods have been developed by searching documents from the knowledge corpus and appending them unconditionally or selectively to the input of LLMs for generation. However, when applying existing methods to different domain-specific problems, poor generalization becomes apparent, leading to fetching incorrect documents or making inaccurate judgments. In this paper, we introduce Self-BioRAG, a framework reliable for biomedical text that specializes in generating explanations, retrieving domain-specific documents, and self-reflecting generated responses. We utilize 84k filtered biomedical instruction sets to train Self-BioRAG that can assess its generated explanations with customized reflective tokens. Our work proves that domain-specific components, such as a retriever, domain-related document corpus, and instruction sets are necessary for adhering to domain-related instructions. Using three major medical question-answering benchmark datasets, experimental results of Self-BioRAG demonstrate significant performance gains by achieving a 7.2% absolute improvement on average over the state-of-the-art open-foundation model with a parameter size of 7B or less. Overall, we analyze that Self-BioRAG finds the clues in the question, retrieves relevant documents if needed, and understands how to answer with information from retrieved documents and encoded knowledge as a medical expert does. We release our data and code for training our framework components and model weights (7B and 13B) to enhance capabilities in biomedical and clinical domains.

  • 4 authors
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Jan 26, 2024

Magneto: Combining Small and Large Language Models for Schema Matching

Recent advances in language models opened new opportunities to address complex schema matching tasks. Schema matching approaches have been proposed that demonstrate the usefulness of language models, but they have also uncovered important limitations: Small language models (SLMs) require training data (which can be both expensive and challenging to obtain), and large language models (LLMs) often incur high computational costs and must deal with constraints imposed by context windows. We present Magneto, a cost-effective and accurate solution for schema matching that combines the advantages of SLMs and LLMs to address their limitations. By structuring the schema matching pipeline in two phases, retrieval and reranking, Magneto can use computationally efficient SLM-based strategies to derive candidate matches which can then be reranked by LLMs, thus making it possible to reduce runtime without compromising matching accuracy. We propose a self-supervised approach to fine-tune SLMs which uses LLMs to generate syntactically diverse training data, and prompting strategies that are effective for reranking. We also introduce a new benchmark, developed in collaboration with domain experts, which includes real biomedical datasets and presents new challenges to schema matching methods. Through a detailed experimental evaluation, using both our new and existing benchmarks, we show that Magneto is scalable and attains high accuracy for datasets from different domains.

  • 5 authors
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Dec 11, 2024

A Survey for Large Language Models in Biomedicine

Recent breakthroughs in large language models (LLMs) offer unprecedented natural language understanding and generation capabilities. However, existing surveys on LLMs in biomedicine often focus on specific applications or model architectures, lacking a comprehensive analysis that integrates the latest advancements across various biomedical domains. This review, based on an analysis of 484 publications sourced from databases including PubMed, Web of Science, and arXiv, provides an in-depth examination of the current landscape, applications, challenges, and prospects of LLMs in biomedicine, distinguishing itself by focusing on the practical implications of these models in real-world biomedical contexts. Firstly, we explore the capabilities of LLMs in zero-shot learning across a broad spectrum of biomedical tasks, including diagnostic assistance, drug discovery, and personalized medicine, among others, with insights drawn from 137 key studies. Then, we discuss adaptation strategies of LLMs, including fine-tuning methods for both uni-modal and multi-modal LLMs to enhance their performance in specialized biomedical contexts where zero-shot fails to achieve, such as medical question answering and efficient processing of biomedical literature. Finally, we discuss the challenges that LLMs face in the biomedicine domain including data privacy concerns, limited model interpretability, issues with dataset quality, and ethics due to the sensitive nature of biomedical data, the need for highly reliable model outputs, and the ethical implications of deploying AI in healthcare. To address these challenges, we also identify future research directions of LLM in biomedicine including federated learning methods to preserve data privacy and integrating explainable AI methodologies to enhance the transparency of LLMs.

  • 17 authors
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Aug 29, 2024

GALAX: Graph-Augmented Language Model for Explainable Reinforcement-Guided Subgraph Reasoning in Precision Medicine

In precision medicine, quantitative multi-omic features, topological context, and textual biological knowledge play vital roles in identifying disease-critical signaling pathways and targets. Existing pipelines capture only part of these-numerical omics ignore topological context, text-centric LLMs lack quantitative grounded reasoning, and graph-only models underuse node semantics and the generalization of LLMs-limiting mechanistic interpretability. Although Process Reward Models (PRMs) aim to guide reasoning in LLMs, they remain limited by unreliable intermediate evaluation, and vulnerability to reward hacking with computational cost. These gaps motivate integrating quantitative multi-omic signals, topological structure with node annotations, and literature-scale text via LLMs, using subgraph reasoning as the principle bridge linking numeric evidence, topological knowledge and language context. Therefore, we propose GALAX (Graph Augmented LAnguage model with eXplainability), an innovative framework that integrates pretrained Graph Neural Networks (GNNs) into Large Language Models (LLMs) via reinforcement guided by a Graph Process Reward Model (GPRM), which generates disease-relevant subgraphs in a step-wise manner initiated by an LLM and iteratively evaluated by a pretrained GNN, enabling process-level supervision without explicit intermediate reasoning annotations. As an application, we also introduced Target-QA, a benchmark combining CRISPR-identified targets, multi-omic profiles, and biomedical graph knowledge across diverse cancer cell lines, which enables GNN pretraining for supervising step-wise graph construction and supports long-context reasoning over text-numeric graphs (TNGs), providing a scalable and biologically grounded framework for explainable, reinforcement-guided subgraph reasoning toward reliable and interpretable target and pathway discovery in precision medicine.

  • 7 authors
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Sep 25, 2025

Singular Value Few-shot Adaptation of Vision-Language Models

Vision-language models (VLMs) like CLIP have shown impressive zero-shot and few-shot learning capabilities across diverse applications. However, adapting these models to new fine-grained domains remains difficult due to reliance on prompt engineering and the high cost of full model fine-tuning. Existing adaptation approaches rely on augmented components, such as prompt tokens and adapter modules, which could limit adaptation quality, destabilize the model, and compromise the rich knowledge learned during pretraining. In this work, we present CLIP-SVD, a novel multi-modal and parameter-efficient adaptation technique that leverages Singular Value Decomposition (SVD) to modify the internal parameter space of CLIP without injecting additional modules. Specifically, we fine-tune only the singular values of the CLIP parameter matrices to rescale the basis vectors for domain adaptation while retaining the pretrained model. This design enables enhanced adaptation performance using only 0.04\% of the model's total parameters and better preservation of its generalization ability. CLIP-SVD achieves state-of-the-art classification results on 11 natural and 10 biomedical datasets, outperforming previous methods in both accuracy and generalization under few-shot settings. Additionally, we leverage a natural language-based approach to analyze the effectiveness and dynamics of the CLIP adaptation to allow interpretability of CLIP-SVD. The code is publicly available at https://github.com/HealthX-Lab/CLIP-SVD.

  • 3 authors
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Sep 3, 2025 2

Potential of Multimodal Large Language Models for Data Mining of Medical Images and Free-text Reports

Medical images and radiology reports are crucial for diagnosing medical conditions, highlighting the importance of quantitative analysis for clinical decision-making. However, the diversity and cross-source heterogeneity of these data challenge the generalizability of current data-mining methods. Multimodal large language models (MLLMs) have recently transformed many domains, significantly affecting the medical field. Notably, Gemini-Vision-series (Gemini) and GPT-4-series (GPT-4) models have epitomized a paradigm shift in Artificial General Intelligence (AGI) for computer vision, showcasing their potential in the biomedical domain. In this study, we evaluated the performance of the Gemini, GPT-4, and 4 popular large models for an exhaustive evaluation across 14 medical imaging datasets, including 5 medical imaging categories (dermatology, radiology, dentistry, ophthalmology, and endoscopy), and 3 radiology report datasets. The investigated tasks encompass disease classification, lesion segmentation, anatomical localization, disease diagnosis, report generation, and lesion detection. Our experimental results demonstrated that Gemini-series models excelled in report generation and lesion detection but faces challenges in disease classification and anatomical localization. Conversely, GPT-series models exhibited proficiency in lesion segmentation and anatomical localization but encountered difficulties in disease diagnosis and lesion detection. Additionally, both the Gemini series and GPT series contain models that have demonstrated commendable generation efficiency. While both models hold promise in reducing physician workload, alleviating pressure on limited healthcare resources, and fostering collaboration between clinical practitioners and artificial intelligence technologies, substantial enhancements and comprehensive validations remain imperative before clinical deployment.

  • 14 authors
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Jul 8, 2024

The SourceData-NLP dataset: integrating curation into scientific publishing for training large language models

Introduction: The scientific publishing landscape is expanding rapidly, creating challenges for researchers to stay up-to-date with the evolution of the literature. Natural Language Processing (NLP) has emerged as a potent approach to automating knowledge extraction from this vast amount of publications and preprints. Tasks such as Named-Entity Recognition (NER) and Named-Entity Linking (NEL), in conjunction with context-dependent semantic interpretation, offer promising and complementary approaches to extracting structured information and revealing key concepts. Results: We present the SourceData-NLP dataset produced through the routine curation of papers during the publication process. A unique feature of this dataset is its emphasis on the annotation of bioentities in figure legends. We annotate eight classes of biomedical entities (small molecules, gene products, subcellular components, cell lines, cell types, tissues, organisms, and diseases), their role in the experimental design, and the nature of the experimental method as an additional class. SourceData-NLP contains more than 620,000 annotated biomedical entities, curated from 18,689 figures in 3,223 papers in molecular and cell biology. We illustrate the dataset's usefulness by assessing BioLinkBERT and PubmedBERT, two transformers-based models, fine-tuned on the SourceData-NLP dataset for NER. We also introduce a novel context-dependent semantic task that infers whether an entity is the target of a controlled intervention or the object of measurement. Conclusions: SourceData-NLP's scale highlights the value of integrating curation into publishing. Models trained with SourceData-NLP will furthermore enable the development of tools able to extract causal hypotheses from the literature and assemble them into knowledge graphs.

  • 4 authors
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Oct 31, 2023

Zhongjing: Enhancing the Chinese Medical Capabilities of Large Language Model through Expert Feedback and Real-world Multi-turn Dialogue

Recent advances in Large Language Models (LLMs) have achieved remarkable breakthroughs in understanding and responding to user intents. However, their performance lag behind general use cases in some expertise domains, such as Chinese medicine. Existing efforts to incorporate Chinese medicine into LLMs rely on Supervised Fine-Tuning (SFT) with single-turn and distilled dialogue data. These models lack the ability for doctor-like proactive inquiry and multi-turn comprehension and cannot align responses with experts' intentions. In this work, we introduce Zhongjing, the first Chinese medical LLaMA-based LLM that implements an entire training pipeline from continuous pre-training, SFT, to Reinforcement Learning from Human Feedback (RLHF). Additionally, we construct a Chinese multi-turn medical dialogue dataset of 70,000 authentic doctor-patient dialogues, CMtMedQA, which significantly enhances the model's capability for complex dialogue and proactive inquiry initiation. We also define a refined annotation rule and evaluation criteria given the unique characteristics of the biomedical domain. Extensive experimental results show that Zhongjing outperforms baselines in various capacities and matches the performance of ChatGPT in some abilities, despite the 100x parameters. Ablation studies also demonstrate the contributions of each component: pre-training enhances medical knowledge, and RLHF further improves instruction-following ability and safety. Our code, datasets, and models are available at https://github.com/SupritYoung/Zhongjing.

  • 7 authors
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Aug 7, 2023

BudgetLongformer: Can we Cheaply Pretrain a SotA Legal Language Model From Scratch?

Pretrained transformer models have achieved state-of-the-art results in many tasks and benchmarks recently. Many state-of-the-art Language Models (LMs), however, do not scale well above the threshold of 512 input tokens. In specialized domains though (such as legal, scientific or biomedical), models often need to process very long text (sometimes well above 10000 tokens). Even though many efficient transformers have been proposed (such as Longformer, BigBird or FNet), so far, only very few such efficient models are available for specialized domains. Additionally, since the pretraining process is extremely costly in general - but even more so as the sequence length increases - it is often only in reach of large research labs. One way of making pretraining cheaper is the Replaced Token Detection (RTD) task, by providing more signal during training, since the loss can be computed over all tokens. In this work, we train Longformer models with the efficient RTD task on legal data to showcase that pretraining efficient LMs is possible using much less compute. We evaluate the trained models on challenging summarization tasks requiring the model to summarize long texts to show to what extent the models can achieve good performance on downstream tasks. We find that both the small and base models outperform their baselines on the in-domain BillSum and out-of-domain PubMed tasks in their respective parameter range. We publish our code and models for research purposes.

  • 2 authors
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Nov 30, 2022

Medical Adaptation of Large Language and Vision-Language Models: Are We Making Progress?

Several recent works seek to develop foundation models specifically for medical applications, adapting general-purpose large language models (LLMs) and vision-language models (VLMs) via continued pretraining on publicly available biomedical corpora. These works typically claim that such domain-adaptive pretraining (DAPT) improves performance on downstream medical tasks, such as answering medical licensing exam questions. In this paper, we compare seven public "medical" LLMs and two VLMs against their corresponding base models, arriving at a different conclusion: all medical VLMs and nearly all medical LLMs fail to consistently improve over their base models in the zero-/few-shot prompting regime for medical question-answering (QA) tasks. For instance, across the tasks and model pairs we consider in the 3-shot setting, medical LLMs only outperform their base models in 12.1% of cases, reach a (statistical) tie in 49.8% of cases, and are significantly worse than their base models in the remaining 38.2% of cases. Our conclusions are based on (i) comparing each medical model head-to-head, directly against the corresponding base model; (ii) optimizing the prompts for each model separately; and (iii) accounting for statistical uncertainty in comparisons. While these basic practices are not consistently adopted in the literature, our ablations show that they substantially impact conclusions. Our findings suggest that state-of-the-art general-domain models may already exhibit strong medical knowledge and reasoning capabilities, and offer recommendations to strengthen the conclusions of future studies.

  • 4 authors
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Nov 6, 2024