Biomedical Relation Extraction Research Articles

RegulaTome: a corpus of typed, directed, and signed relations between biomedical entities in the scientific literature.

In the field of biomedical text mining, the ability to extract relations from the literature is crucial for advancing both theoretical research and practical applications. There is a notable shortage of corpora designed to enhance the extraction of multiple types of relations, particularly focusing on proteins and protein-containing entities such as complexes and families, as well as chemicals. In this work, we present RegulaTome, a corpus that overcomes the limitations of several existing biomedical relation extraction (RE) corpora, many of which concentrate on single-type relations at the sentence level. RegulaTome stands out by offering 16 961 relations annotated in >2500 documents, making it the most extensive dataset of its kind to date. This corpus is specifically designed to cover a broader spectrum of >40 relation types beyond those traditionally explored, setting a new benchmark in the complexity and depth of biomedical RE tasks. Our corpus both broadens the scope of detected relations and allows for achieving noteworthy accuracy in RE. A transformer-based model trained on this corpus has demonstrated a promising F1-score (66.6%) for a task of this complexity, underscoring the effectiveness of our approach in accurately identifying and categorizing a wide array of biological relations. This achievement highlights RegulaTome's potential to significantly contribute to the development of more sophisticated, efficient, and accurate RE systems to tackle biomedical tasks. Finally, a run of the trained RE system on all PubMed abstracts and PMC Open Access full-text documents resulted in >18 million relations, extracted from the entire biomedical literature.

Integrating graph convolutional networks to enhance prompt learning for biomedical relation extraction

Background and Objective:Biomedical relation extraction aims to reveal the relation between entities in medical texts. Currently, the relation extraction models that have attracted much attention are mainly to fine-tune the pre-trained language models (PLMs) or add template prompt learning, which also limits the ability of the model to deal with grammatical dependencies. Graph convolutional networks (GCNs) can play an important role in processing syntactic dependencies in biomedical texts. Methods:In this work, we propose a biomedical relation extraction model that fuses GCNs enhanced prompt learning to handle limitations in syntactic dependencies and achieve good performance. Specifically, we propose a model that combines prompt learning with GCNs for relation extraction, by integrating the syntactic dependency information analyzed by GCNs into the prompt learning model, by predicting the correspondence with [MASK] tokens labels for relation extraction. Results:Our model achieved F1 scores of 85.57%, 80.15%, 95.10%, and 84.11% in the biomedical relation extraction datasets GAD, ChemProt, PGR, and DDI, respectively, all of which outperform some existing baseline models. Conclusions:In this paper, we propose enhancing prompt learning through GCNs, integrating syntactic information into biomedical relation extraction tasks. Experimental results show that our proposed method achieves excellent performance in the biomedical relation extraction task.

Integrating deep learning architectures for enhanced biomedical relation extraction: a pipeline approach.

Biomedical relation extraction from scientific publications is a key task in biomedical natural language processing (NLP) and can facilitate the creation of large knowledge bases, enable more efficient knowledge discovery, and accelerate evidence synthesis. In this paper, building upon our previous effort in the BioCreative VIII BioRED Track, we propose an enhanced end-to-end pipeline approach for biomedical relation extraction (RE) and novelty detection (ND) that effectively leverages existing datasets and integrates state-of-the-art deep learning methods. Our pipeline consists of four tasks performed sequentially: named entity recognition (NER), entity linking (EL), RE, and ND. We trained models using the BioRED benchmark corpus that was the basis of the shared task. We explored several methods for each task and combinations thereof: for NER, we compared a BERT-based sequence labeling model that uses the BIO scheme with a span classification model. For EL, we trained a convolutional neural network model for diseases and chemicals and used an existing tool, PubTator 3.0, for mapping other entity types. For RE and ND, we adapted the BERT-based, sentence-bound PURE model to bidirectional and document-level extraction. We also performed extensive hyperparameter tuning to improve model performance. We obtained our best performance using BERT-based models for NER, RE, and ND, and the hybrid approach for EL. Our enhanced and optimized pipeline showed substantial improvement compared to our shared task submission, NER: 93.53 (+3.09), EL: 83.87 (+9.73), RE: 46.18 (+15.67), and ND: 38.86 (+14.9). While the performances of the NER and EL models are reasonably high, RE and ND tasks remain challenging at the document level. Further enhancements to the dataset could enable more accurate and useful models for practical use. We provide our models and code at https://github.com/janinaj/e2eBioMedRE/. Database URL: https://github.com/janinaj/e2eBioMedRE/.

The overview of the BioRED (Biomedical Relation Extraction Dataset) track at BioCreative VIII.

The BioRED track at BioCreative VIII calls for a community effort to identify, semantically categorize, and highlight the novelty factor of the relationships between biomedical entities in unstructured text. Relation extraction is crucial for many biomedical natural language processing (NLP) applications, from drug discovery to custom medical solutions. The BioRED track simulates a real-world application of biomedical relationship extraction, and as such, considers multiple biomedical entity types, normalized to their specific corresponding database identifiers, as well as defines relationships between them in the documents. The challenge consisted of two subtasks: (i) in Subtask 1, participants were given the article text and human expert annotated entities, and were asked to extract the relation pairs, identify their semantic type and the novelty factor, and (ii) in Subtask 2, participants were given only the article text, and were asked to build an end-to-end system that could identify and categorize the relationships and their novelty. We received a total of 94 submissions from 14 teams worldwide. The highest F-score performances achieved for the Subtask 1 were: 77.17% for relation pair identification, 58.95% for relation type identification, 59.22% for novelty identification, and 44.55% when evaluating all of the above aspects of the comprehensive relation extraction. The highest F-score performances achieved for the Subtask 2 were: 55.84% for relation pair, 43.03% for relation type, 42.74% for novelty, and 32.75% for comprehensive relation extraction. The entire BioRED track dataset and other challenge materials are available at https://ftp.ncbi.nlm.nih.gov/pub/lu/BC8-BioRED-track/ and https://codalab.lisn.upsaclay.fr/competitions/13377 and https://codalab.lisn.upsaclay.fr/competitions/13378. Database URL: https://ftp.ncbi.nlm.nih.gov/pub/lu/BC8-BioRED-track/https://codalab.lisn.upsaclay.fr/competitions/13377https://codalab.lisn.upsaclay.fr/competitions/13378.

Multi-head CRF classifier for biomedical multi-class named entity recognition on Spanish clinical notes.

The identification of medical concepts from clinical narratives has a large interest in the biomedical scientific community due to its importance in treatment improvements or drug development research. Biomedical named entity recognition (NER) in clinical texts is crucial for automated information extraction, facilitating patient record analysis, drug development, and medical research. Traditional approaches often focus on single-class NER tasks, yet recent advancements emphasize the necessity of addressing multi-class scenarios, particularly in complex biomedical domains. This paper proposes a strategy to integrate a multi-head conditional random field (CRF) classifier for multi-class NER in Spanish clinical documents. Our methodology overcomes overlapping entity instances of different types, a common challenge in traditional NER methodologies, by using a multi-head CRF model. This architecture enhances computational efficiency and ensures scalability for multi-class NER tasks, maintaining high performance. By combining four diverse datasets, SympTEMIST, MedProcNER, DisTEMIST, and PharmaCoNER, we expand the scope of NER to encompass five classes: symptoms, procedures, diseases, chemicals, and proteins. To the best of our knowledge, these datasets combined create the largest Spanish multi-class dataset focusing on biomedical entity recognition and linking for clinical notes, which is important to train a biomedical model in Spanish. We also provide entity linking to the multi-lingual Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) vocabulary, with the eventual goal of performing biomedical relation extraction. Through experimentation and evaluation of Spanish clinical documents, our strategy provides competitive results against single-class NER models. For NER, our system achieves a combined micro-averaged F1-score of 78.73, with clinical mentions normalized to SNOMED CT with an end-to-end F1-score of 54.51. The code to run our system is publicly available at https://github.com/ieeta-pt/Multi-Head-CRF. Database URL: https://github.com/ieeta-pt/Multi-Head-CRF.

Leveraging shortest dependency paths in low-resource biomedical relation extraction

BackgroundBiomedical Relation Extraction (RE) is essential for uncovering complex relationships between biomedical entities within text. However, training RE classifiers is challenging in low-resource biomedical applications with few labeled examples.MethodsWe explore the potential of Shortest Dependency Paths (SDPs) to aid biomedical RE, especially in situations with limited labeled examples. In this study, we suggest various approaches to employ SDPs when creating word and sentence representations under supervised, semi-supervised, and in-context-learning settings.ResultsThrough experiments on three benchmark biomedical text datasets, we find that incorporating SDP-based representations enhances the performance of RE classifiers. The improvement is especially notable when working with small amounts of labeled data.ConclusionSDPs offer valuable insights into the complex sentence structure found in many biomedical text passages. Our study introduces several straightforward techniques that, as demonstrated experimentally, effectively enhance the accuracy of RE classifiers.

Towards discovery: an end-to-end system for uncovering novel biomedical relations.

Biomedical relation extraction is an ongoing challenge within the natural language processing community. Its application is important for understanding scientific biomedical literature, with many use cases, such as drug discovery, precision medicine, disease diagnosis, treatment optimization and biomedical knowledge graph construction. Therefore, the development of a tool capable of effectively addressing this task holds the potential to improve knowledge discovery by automating the extraction of relations from research manuscripts. The first track in the BioCreative VIII competition extended the scope of this challenge by introducing the detection of novel relations within the literature. This paper describes that our participation system initially focused on jointly extracting and classifying novel relations between biomedical entities. We then describe our subsequent advancement to an end-to-end model. Specifically, we enhanced our initial system by incorporating it into a cascading pipeline that includes a tagger and linker module. This integration enables the comprehensive extraction of relations and classification of their novelty directly from raw text. Our experiments yielded promising results, and our tagger module managed to attain state-of-the-art named entity recognition performance, with a micro F1-score of 90.24, while our end-to-end system achieved a competitive novelty F1-score of 24.59. The code to run our system is publicly available at https://github.com/ieeta-pt/BioNExt. Database URL: https://github.com/ieeta-pt/BioNExt.

Document-level biomedical relation extraction via hierarchical tree graph and relation segmentation module.

Biomedical relation extraction at the document level (Bio-DocRE) involves extracting relation instances from biomedical texts that span multiple sentences, often containing various entity concepts such as genes, diseases, chemicals, variants, etc. Currently, this task is usually implemented based on graphs or transformers. However, most work directly models entity features to relation prediction, ignoring the effectiveness of entity pair information as an intermediate state for relation prediction. In this article, we decouple this task into a three-stage process to capture sufficient information for improving relation prediction. We propose an innovative framework HTGRS for Bio-DocRE, which constructs a hierarchical tree graph (HTG) to integrate key information sources in the document, achieving relation reasoning based on entity. In addition, inspired by the idea of semantic segmentation, we conceptualize the task as a table-filling problem and develop a relation segmentation (RS) module to enhance relation reasoning based on the entity pair. Extensive experiments on three datasets show that the proposed framework outperforms the state-of-the-art methods and achieves superior performance. Our source code is available at https://github.com/passengeryjy/HTGRS.

A Knowledge-enhanced model with syntactic-aware attentive graph convolutional network for biomedical entity and relation extraction

A Knowledge-enhanced model with syntactic-aware attentive graph convolutional network for biomedical entity and relation extraction

LEAP: LLM instruction-example adaptive prompting framework for biomedical relation extraction.

To investigate the demonstration in large language models (LLMs) for biomedical relation extraction. This study introduces a framework comprising three types of adaptive tuning methods to assess their impacts and effectiveness. Our study was conducted in two phases. Initially, we analyzed a range of demonstration components vital for LLMs' biomedical data capabilities, including task descriptions and examples, experimenting with various combinations. Subsequently, we introduced the LLM instruction-example adaptive prompting (LEAP) framework, including instruction adaptive tuning, example adaptive tuning, and instruction-example adaptive tuning methods. This framework aims to systematically investigate both adaptive task descriptions and adaptive examples within the demonstration. We assessed the performance of the LEAP framework on the DDI, ChemProt, and BioRED datasets, employing LLMs such as Llama2-7b, Llama2-13b, and MedLLaMA_13B. Our findings indicated that Instruction + Options + Example and its expanded form substantially improved F1 scores over the standard Instruction + Options mode for zero-shot LLMs. The LEAP framework, particularly through its example adaptive prompting, demonstrated superior performance over conventional instruction tuning across all models. Notably, the MedLLAMA_13B model achieved an exceptional F1 score of 95.13 on the ChemProt dataset using this method. Significant improvements were also observed in the DDI 2013 and BioRED datasets, confirming the method's robustness in sophisticated data extraction scenarios. The LEAP framework offers a compelling strategy for enhancing LLM training strategies, steering away from extensive fine-tuning towards more dynamic and contextually enriched prompting methodologies, showcasing in biomedical relation extraction.

Location-enhanced syntactic knowledge for biomedical relation extraction

Biomedical relation extraction has long been considered a challenging task due to the specialization and complexity of biomedical texts. Syntactic knowledge has been widely employed in existing research to enhance relation extraction, providing guidance for the semantic understanding and text representation of models. However, the utilization of syntactic knowledge in most studies is not exhaustive, and there is often a lack of fine-grained noise reduction, leading to confusion in relation classification. In this paper, we propose an attention generator that comprehensively considers both syntactic dependency type information and syntactic position information to distinguish the importance of different dependency connections. Additionally, we integrate positional information, dependency type information, and word representations together to introduce location-enhanced syntactic knowledge for guiding our biomedical relation extraction. Experimental results on three widely used English benchmark datasets in the biomedical domain consistently outperform a range of baseline models, demonstrating that our approach not only makes full use of syntactic knowledge but also effectively reduces the impact of noisy words.

DUVEL: an active-learning annotated biomedical corpus for the recognition of oligogenic combinations.

While biomedical relation extraction (bioRE) datasets have been instrumental in the development of methods to support biocuration of single variants from texts, no datasets are currently available for the extraction of digenic or even oligogenic variant relations, despite the reports in literature that epistatic effects between combinations of variants in different loci (or genes) are important to understand disease etiologies. This work presents the creation of a unique dataset of oligogenic variant combinations, geared to train tools to help in the curation of scientific literature. To overcome the hurdles associated with the number of unlabelled instances and the cost of expertise, active learning (AL) was used to optimize the annotation, thus getting assistance in finding the most informative subset of samples to label. By pre-annotating 85 full-text articles containing the relevant relations from the Oligogenic Diseases Database (OLIDA) with PubTator, text fragments featuring potential digenic variant combinations, i.e. gene-variant-gene-variant, were extracted. The resulting fragments of texts were annotated with ALAMBIC, an AL-based annotation platform. The resulting dataset, called DUVEL, is used to fine-tune four state-of-the-art biomedical language models: BiomedBERT, BiomedBERT-large, BioLinkBERT and BioM-BERT. More than 500 000 text fragments were considered for annotation, finally resulting in a dataset with 8442 fragments, 794 of them being positive instances, covering 95% of the original annotated articles. When applied to gene-variant pair detection, BiomedBERT-large achieves the highest F1 score (0.84) after fine-tuning, demonstrating significant improvement compared to the non-fine-tuned model, underlining the relevance of the DUVEL dataset. This study shows how AL may play an important role in the creation of bioRE dataset relevant for biomedical curation applications. DUVEL provides a unique biomedical corpus focusing on 4-ary relations between two genes and two variants. It is made freely available for research on GitHub and Hugging Face. Database URL: https://huggingface.co/datasets/cnachteg/duvel or https://doi.org/10.57967/hf/1571.

Few-shot biomedical relation extraction using data augmentation and domain information

Relation extraction (RE) plays a pivotal role in biomedical information extraction. However, traditional approaches are often limited by high data annotation costs and extensive time investments. To address this challenge, this study proposes an innovative few-shot learning approach for biomedical RE tasks that utilizes data augmentation and domain information. Specifically, this method enhances the diversity of training data through a synthesized data augmentation strategy. At the same time, it combines domain information with prompt learning techniques. By incorporating domain information, the model’s generalization capability for rare data instances is improved. Furthermore, the prompt learning approach, by integrating prompt templates into the model input, guides the pre-trained language model to more accurately adapt to the RE task. Our model demonstrated exceptional performance in three different biomedical RE tasks, particularly on the I2B2-2010 RE dataset. In the 1-shot, 10-shot, and 50-shot settings, the F1 scores increased by 14.38%, 9.50%, and 6.05%, respectively.

Prompt Tuning in Biomedical Relation Extraction.

The online version contains supplementary material available at 10.1007/s41666-024-00162-9.

Distantly Supervised Biomedical Relation Extraction Via Negative Learning and Noisy Student Self-Training.

Biomedical relation extraction aims to identify underlying relationships among entities, such as gene associations and drug interactions, within biomedical texts. Despite advancements in relation extraction in general knowledge domains, the scarcity of labeled training data remains a significant challenge in the biomedical field. This paper provides a novel approach for biomedical relation extraction that leverages a noisy student self-training strategy combined with negative learning. This method addresses the challenge of data insufficiency by utilizing distantly supervised data to generate high-quality labeled samples. Negative learning, as opposed to traditional positive learning, offers a more robust mechanism to discern and relabel noisy samples, preventing model overfitting. The integration of these techniques ensures enhanced noise reduction and relabeling capabilities, leading to improved performance even with noisy datasets. Experimental results demonstrate the effectiveness of the proposed framework in mitigating the impact of noisy data and outperforming existing benchmarks.

Joint Biomedical Entity and Relation Extraction Based on Multi-Granularity Convolutional Tokens Pairs of Labeling

Joint Biomedical Entity and Relation Extraction Based on Multi-Granularity Convolutional Tokens Pairs of Labeling

BioEGRE: a linguistic topology enhanced method for biomedical relation extraction based on BioELECTRA and graph pointer neural network

BackgroundAutomatic and accurate extraction of diverse biomedical relations from literature is a crucial component of bio-medical text mining. Currently, stacking various classification networks on pre-trained language models to perform fine-tuning is a common framework to end-to-end solve the biomedical relation extraction (BioRE) problem. However, the sequence-based pre-trained language models underutilize the graphical topology of language to some extent. In addition, sequence-oriented deep neural networks have limitations in processing graphical features.ResultsIn this paper, we propose a novel method for sentence-level BioRE task, BioEGRE (BioELECTRA and Graph pointer neural net-work for Relation Extraction), aimed at leveraging the linguistic topological features. First, the biomedical literature is preprocessed to retain sentences involving pre-defined entity pairs. Secondly, SciSpaCy is employed to conduct dependency parsing; sentences are modeled as graphs based on the parsing results; BioELECTRA is utilized to generate token-level representations, which are modeled as attributes of nodes in the sentence graphs; a graph pointer neural network layer is employed to select the most relevant multi-hop neighbors to optimize representations; a fully-connected neural network layer is employed to generate the sentence-level representation. Finally, the Softmax function is employed to calculate the probabilities. Our proposed method is evaluated on three BioRE tasks: a multi-class (CHEMPROT) and two binary tasks (GAD and EU-ADR). The results show that our method achieves F1-scores of 79.97% (CHEMPROT), 83.31% (GAD), and 83.51% (EU-ADR), surpassing the performance of existing state-of-the-art models.ConclusionThe experimental results on 3 biomedical benchmark datasets demonstrate the effectiveness and generalization of BioEGRE, which indicates that linguistic topology and a graph pointer neural network layer explicitly improve performance for BioRE tasks.

A study of deep active learning methods to reduce labelling efforts in biomedical relation extraction

Automatic biomedical relation extraction (bioRE) is an essential task in biomedical research in order to generate high-quality labelled data that can be used for the development of innovative predictive methods. However, building such fully labelled, high quality bioRE data sets of adequate size for the training of state-of-the-art relation extraction models is hindered by an annotation bottleneck due to limitations on time and expertise of researchers and curators. We show here how Active Learning (AL) plays an important role in resolving this issue and positively improve bioRE tasks, effectively overcoming the labelling limits inherent to a data set. Six different AL strategies are benchmarked on seven bioRE data sets, using PubMedBERT as the base model, evaluating their area under the learning curve (AULC) as well as intermediate results measurements. The results demonstrate that uncertainty-based strategies, such as Least-Confident or Margin Sampling, are statistically performing better in terms of F1-score, accuracy and precision, than other types of AL strategies. However, in terms of recall, a diversity-based strategy, called Core-set, outperforms all strategies. AL strategies are shown to reduce the annotation need (in order to reach a performance at par with training on all data), from 6% to 38%, depending on the data set; with Margin Sampling and Least-Confident Sampling strategies moreover obtaining the best AULCs compared to the Random Sampling baseline. We show through the experiments the importance of using AL methods to reduce the amount of labelling needed to construct high-quality data sets leading to optimal performance of deep learning models. The code and data sets to reproduce all the results presented in the article are available at https://github.com/oligogenic/Deep_active_learning_bioRE.

A hierarchical convolutional model for biomedical relation extraction

Biomedical relation extraction aims to extract the interactive relations between biomedical entities in a sentence. In biomedical literature, the sentence lengths are longer compared to general domain. Because all entity pairs in a sentence share the same contextual features and each of them should be evaluated, the biomedical relation extract task suffers from more serious semantic overlapping and data imbalance problems. In this study, a hierarchical convolutional model is proposed to address these problems. This model organizes the convolution operation in a hierarchical structure. First, after a sentence is divided into several channels by using the semantic structure of a relation instance, a token-level convolution is used to encodes local contextual features of different channels. Then, a channel-level convolution is designed to encode global semantic dependencies of a sentence. The hierarchical convolution is effective to learn contextual features and semantic dependencies relevant to ordered named entities, which enhance the discriminability of a neural network for biomedical relation extraction. The proposed method was evaluated on seven public datasets for three tasks: including protein-protein, drug-drug, and chemical-protein interactions. It outperformed state-of-the-art performance about 3.7% in the F1 score.

Learning entity-oriented representation for biomedical relation extraction

Biomedical Relation Extraction (BioRE) aims to automatically extract semantic relations for given entity pairs and is of great significance in biomedical research. Current popular methods often utilize pretrained language models to extract semantic features from individual input instances, which frequently suffer from overlapping semantics. Overlapping semantics refers to the situation in which a sentence contains multiple entity pairs that share the same context, leading to highly similar information between these entity pairs. In this study, we propose a model for learning Entity-oriented Representation (EoR) that aims to improve the performance of the model by enhancing the discriminability between entity pairs. It contains three modules: sentence representation, entity-oriented representation, and output. The first module learns the global semantic information of the input instance; the second module focuses on extracting the semantic information of the sentence from the target entities; and the third module enhances distinguishability among entity pairs and classifies the relation type. We evaluated our approach on four BioRE tasks with eight datasets, and the experiments showed that our EoR achieved state-of-the-art performance for PPI, DDI, CPI, and DPI tasks. Further analysis demonstrated the benefits of entity-oriented semantic information in handling multiple entity pairs in the BioRE task.