In the era of information overload, natural language processing (NLP) techniques are increasingly needed to support advanced biomedical information management and discovery applications. In this ...paper, we present an in-depth description of SemRep, an NLP system that extracts semantic relations from PubMed abstracts using linguistic principles and UMLS domain knowledge. We also evaluate SemRep on two datasets. In one evaluation, we use a manually annotated test collection and perform a comprehensive error analysis. In another evaluation, we assess SemRep's performance on the CDR dataset, a standard benchmark corpus annotated with causal chemical-disease relationships.
A strict evaluation of SemRep on our manually annotated dataset yields 0.55 precision, 0.34 recall, and 0.42 F
score. A relaxed evaluation, which more accurately characterizes SemRep performance, yields 0.69 precision, 0.42 recall, and 0.52 F
score. An error analysis reveals named entity recognition/normalization as the largest source of errors (26.9%), followed by argument identification (14%) and trigger detection errors (12.5%). The evaluation on the CDR corpus yields 0.90 precision, 0.24 recall, and 0.38 F
score. The recall and the F
score increase to 0.35 and 0.50, respectively, when the evaluation on this corpus is limited to sentence-bound relationships, which represents a fairer evaluation, as SemRep operates at the sentence level.
SemRep is a broad-coverage, interpretable, strong baseline system for extracting semantic relations from biomedical text. It also underpins SemMedDB, a literature-scale knowledge graph based on semantic relations. Through SemMedDB, SemRep has had significant impact in the scientific community, supporting a variety of clinical and translational applications, including clinical decision making, medical diagnosis, drug repurposing, literature-based discovery and hypothesis generation, and contributing to improved health outcomes. In ongoing development, we are redesigning SemRep to increase its modularity and flexibility, and addressing weaknesses identified in the error analysis.
Coreference resolution is one of the fundamental and challenging tasks in natural language processing. Resolving coreference successfully can have a significant positive effect on downstream natural ...language processing tasks, such as information extraction and question answering. The importance of coreference resolution for biomedical text analysis applications has increasingly been acknowledged. One of the difficulties in coreference resolution stems from the fact that distinct types of coreference (e.g., anaphora, appositive) are expressed with a variety of lexical and syntactic means (e.g., personal pronouns, definite noun phrases), and that resolution of each combination often requires a different approach. In the biomedical domain, it is common for coreference annotation and resolution efforts to focus on specific subcategories of coreference deemed important for the downstream task. In the current work, we aim to address some of these concerns regarding coreference resolution in biomedical text. We propose a general, modular framework underpinned by a smorgasbord architecture (Bio-SCoRes), which incorporates a variety of coreference types, their mentions and allows fine-grained specification of resolution strategies to resolve coreference of distinct coreference type-mention pairs. For development and evaluation, we used a corpus of structured drug labels annotated with fine-grained coreference information. In addition, we evaluated our approach on two other corpora (i2b2/VA discharge summaries and protein coreference dataset) to investigate its generality and ease of adaptation to other biomedical text types. Our results demonstrate the usefulness of our novel smorgasbord architecture. The specific pipelines based on the architecture perform successfully in linking coreferential mention pairs, while we find that recognition of full mention clusters is more challenging. The corpus of structured drug labels (SPL) as well as the components of Bio-SCoRes and some of the pipelines based on it are publicly available at https://github.com/kilicogluh/Bio-SCoRes. We believe that Bio-SCoRes can serve as a strong and extensible baseline system for coreference resolution of biomedical text.
Abstract
An estimated quarter of a trillion US dollars is invested in the biomedical research enterprise annually. There is growing alarm that a significant portion of this investment is wasted ...because of problems in reproducibility of research findings and in the rigor and integrity of research conduct and reporting. Recent years have seen a flurry of activities focusing on standardization and guideline development to enhance the reproducibility and rigor of biomedical research. Research activity is primarily communicated via textual artifacts, ranging from grant applications to journal publications. These artifacts can be both the source and the manifestation of practices leading to research waste. For example, an article may describe a poorly designed experiment, or the authors may reach conclusions not supported by the evidence presented. In this article, we pose the question of whether biomedical text mining techniques can assist the stakeholders in the biomedical research enterprise in doing their part toward enhancing research integrity and rigor. In particular, we identify four key areas in which text mining techniques can make a significant contribution: plagiarism/fraud detection, ensuring adherence to reporting guidelines, managing information overload and accurate citation/enhanced bibliometrics. We review the existing methods and tools for specific tasks, if they exist, or discuss relevant research that can provide guidance for future work. With the exponential increase in biomedical research output and the ability of text mining approaches to perform automatic tasks at large scale, we propose that such approaches can support tools that promote responsible research practices, providing significant benefits for the biomedical research enterprise.
Comments in PubMed are usually short papers for supporting or refuting claims, or discussing methods and findings in original articles. This study aims to explore whether they can be used as a quick ...and reliable evidence appraisal instrument for promoting research findings into practice, especially in emergency situations such as COVID-19 in which only missing, incomplete or uncertain evidence is available.
Evidence-comment networks (ECNs) were constructed by linking COVID-19-related articles to the commentaries (letters, editorials or brief correspondence) they received. PubTator Central was used to extract entities with a high volume of comments from the titles and abstracts of the articles. Among them, six drugs were selected, and their evidence assertions were analysed by exploring the structural information in the ECNs as well as the sentiment of the comments (positive, negative, neutral). Recommendations in WHO guidelines were used as the gold standard control to validate the consistency, coverage and efficiency of comments in reshaping clinical knowledge claims.
The overall positive/negative sentiments of comments were aligned with recommendations for/against the corresponding treatments in the WHO guidelines. Comment topics covered all significant points of evidence appraisal and beyond. Furthermore, comments may indicate the uncertainty regarding drug use for clinical practice. Half of the critical comments emerged 4.25 months earlier on average than the guideline release.
Comments have the potential as a support tool for rapid evidence appraisal as they have a selection effect by appraising the benefits, limitations and other clinical practice issues of concern in existing evidence. We suggest as a future direction an appraisal framework based on the comment topics and sentiment orientations to leverage the potential of scientific commentaries supporting evidence appraisal and decision-making.
Due to the nature of scientific methodology, research articles are rich in speculative and tentative statements, also known as hedges. We explore a linguistically motivated approach to the problem of ...recognizing such language in biomedical research articles. Our approach draws on prior linguistic work as well as existing lexical resources to create a dictionary of hedging cues and extends it by introducing syntactic patterns. Furthermore, recognizing that hedging cues differ in speculative strength, we assign them weights in two ways: automatically using the information gain (IG) measure and semi-automatically based on their types and centrality to hedging. Weights of hedging cues are used to determine the speculative strength of sentences.
We test our system on two publicly available hedging datasets. On the fruit-fly dataset, we achieve a precision-recall breakeven point (BEP) of 0.85 using the semi-automatic weighting scheme and a lower BEP of 0.80 with the information gain weighting scheme. These results are competitive with the previously reported best results (BEP of 0.85). On the BMC dataset, using semi-automatic weighting yields a BEP of 0.82, a statistically significant improvement (p <0.01) over the previously reported best result (BEP of 0.76), while information gain weighting yields a BEP of 0.70.
Our results demonstrate that speculative language can be recognized successfully with a linguistically motivated approach and confirms that selection of hedging devices affects the speculative strength of the sentence, which can be captured reasonably by weighting the hedging cues. The improvement obtained on the BMC dataset with a semi-automatic weighting scheme indicates that our linguistically oriented approach is more portable than the machine-learning based approaches. Lower performance obtained with the information gain weighting scheme suggests that this method may benefit from a larger, manually annotated corpus for automatically inducing the weights.
Consumers increasingly use online resources for their health information needs. While current search engines can address these needs to some extent, they generally do not take into account that most ...health information needs are complex and can only fully be expressed in natural language. Consumer health question answering (QA) systems aim to fill this gap. A major challenge in developing consumer health QA systems is extracting relevant semantic content from the natural language questions (question understanding). To develop effective question understanding tools, question corpora semantically annotated for relevant question elements are needed. In this paper, we present a two-part consumer health question corpus annotated with several semantic categories: named entities, question triggers/types, question frames, and question topic. The first part (CHQA-email) consists of relatively long email requests received by the U.S. National Library of Medicine (NLM) customer service, while the second part (CHQA-web) consists of shorter questions posed to MedlinePlus search engine as queries. Each question has been annotated by two annotators. The annotation methodology is largely the same between the two parts of the corpus; however, we also explain and justify the differences between them. Additionally, we provide information about corpus characteristics, inter-annotator agreement, and our attempts to measure annotation confidence in the absence of adjudication of annotations.
The resulting corpus consists of 2614 questions (CHQA-email: 1740, CHQA-web: 874). Problems are the most frequent named entities, while treatment and general information questions are the most common question types. Inter-annotator agreement was generally modest: question types and topics yielded highest agreement, while the agreement for more complex frame annotations was lower. Agreement in CHQA-web was consistently higher than that in CHQA-email. Pairwise inter-annotator agreement proved most useful in estimating annotation confidence.
To our knowledge, our corpus is the first focusing on annotation of uncurated consumer health questions. It is currently used to develop machine learning-based methods for question understanding. We make the corpus publicly available to stimulate further research on consumer health QA.
Biomedical knowledge claims are often expressed as hypotheses, speculations, or opinions, rather than explicit facts (propositions). Much biomedical text mining has focused on extracting propositions ...from biomedical literature. One such system is SemRep, which extracts propositional content in the form of subject-predicate-object triples called predications. In this study, we investigated the feasibility of assessing the factuality level of SemRep predications to provide more nuanced distinctions between predications for downstream applications. We annotated semantic predications extracted from 500 PubMed abstracts with seven factuality values (fact, probable, possible, doubtful, counterfact, uncommitted, and conditional). We extended a rule-based, compositional approach that uses lexical and syntactic information to predict factuality levels. We compared this approach to a supervised machine learning method that uses a rich feature set based on the annotated corpus. Our results indicate that the compositional approach is more effective than the machine learning method in recognizing the factuality values of predications. The annotated corpus as well as the source code and binaries for factuality assignment are publicly available. We will also incorporate the results of the better performing compositional approach into SemMedDB, a PubMed-scale repository of semantic predications extracted using SemRep.
Non-pharmaceutical interventions (NPI) have great potential to improve cognitive function but limited investigation to discover NPI repurposing for Alzheimer's Disease (AD). This is the first study ...to develop an innovative framework to extract and represent NPI information from biomedical literature in a knowledge graph (KG), and train link prediction models to repurpose novel NPIs for AD prevention. We constructed a comprehensive KG, called ADInt, by extracting NPI information from biomedical literature. We used the previously-created SuppKG and NPI lexicon to identify NPI entities. Four KG embedding models (i.e., TransE, RotatE, DistMult and ComplEX) and two novel graph convolutional network models (i.e., R-GCN and CompGCN) were trained and compared to learn the representation of ADInt. Models were evaluated and compared on two test sets (time slice and clinical trial ground truth) and the best performing model was used to predict novel NPIs for AD. Discovery patterns were applied to generate mechanistic pathways for high scoring candidates. The ADInt has 162,212 nodes and 1,017,284 edges. R-GCN performed best in time slice (MR = 5.2054, Hits@10 = 0.8496) and clinical trial ground truth (MR = 3.4996, Hits@10 = 0.9192) test sets. After evaluation by domain experts, 10 novel dietary supplements and 10 complementary and integrative health were proposed from the score table calculated by R-GCN. Among proposed novel NPIs, we found plausible mechanistic pathways for photodynamic therapy and Choerospondias axillaris to prevent AD, and validated psychotherapy and manual therapy techniques using real-world data analysis. The proposed framework shows potential for discovering new NPIs for AD prevention and understanding their mechanistic pathways.
Semantic relations increasingly underpin biomedical text mining and knowledge discovery applications. The success of such practical applications crucially depends on the quality of extracted ...relations, which can be assessed against a gold standard reference. Most such references in biomedical text mining focus on narrow subdomains and adopt different semantic representations, rendering them difficult to use for benchmarking independently developed relation extraction systems. In this article, we present a multi-phase gold standard annotation study, in which we annotated 500 sentences randomly selected from MEDLINE abstracts on a wide range of biomedical topics with 1371 semantic predications. The UMLS Metathesaurus served as the main source for conceptual information and the UMLS Semantic Network for relational information. We measured interannotator agreement and analyzed the annotations closely to identify some of the challenges in annotating biomedical text with relations based on an ontology or a terminology.
We obtain fair to moderate interannotator agreement in the practice phase (0.378-0.475). With improved guidelines and additional semantic equivalence criteria, the agreement increases by 12% (0.415 to 0.536) in the main annotation phase. In addition, we find that agreement increases to 0.688 when the agreement calculation is limited to those predications that are based only on the explicitly provided UMLS concepts and relations.
While interannotator agreement in the practice phase confirms that conceptual annotation is a challenging task, the increasing agreement in the main annotation phase points out that an acceptable level of agreement can be achieved in multiple iterations, by setting stricter guidelines and establishing semantic equivalence criteria. Mapping text to ontological concepts emerges as the main challenge in conceptual annotation. Annotating predications involving biomolecular entities and processes is particularly challenging. While the resulting gold standard is mainly intended to serve as a test collection for our semantic interpreter, we believe that the lessons learned are applicable generally.
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