Assessing Citation Integrity in Biomedical Publications: Corpus Annotation and NLP Models.

MOTIVATION: Citations have a fundamental role in scholarly communication and assessment. Citation accuracy and transparency is crucial for the integrity of scientific evidence. In this work, we focus on quotation errors, errors in citation content that can distort the scientific evidence and that are hard to detect for humans. We construct a corpus and propose natural language processing (NLP) methods to identify such errors in biomedical publications. RESULTS: We manually annotated 100 highly-cited biomedical publications (reference articles) and citations to them. The annotation involved labeling citation context in the citing article, relevant evidence sentences in the reference article, and the accuracy of the citation. A total of 3,063 citation instances were annotated (39.18% with accuracy errors). For NLP, we combined a sentence retriever with a fine-tuned claim verification model to label citations as accurate, not_accurate, or irrelevant. We also explored few-shot in-context learning with generative large language models. The best performing model-which uses citation sentences as citation context, the BM25 model with MonoT5 reranker for retrieving top-20 sentences, and a fine-tuned MultiVerS model for accuracy label classification-yielded 0.59 micro-F1 and 0.52 macro-F1 score. GPT-4 in-context learning performed better in identifying accurate citations, but it lagged for erroneous citations (0.65 micro-F1, 0.45 macro-F1). Citation quotation errors are often subtle, and it is currently challenging for NLP models to identify erroneous citations. With further improvements, the models could serve to improve citation quality and accuracy. AVAILABILITY: We make the corpus and the best-performing NLP model publicly available at https://github.com/ScienceNLP-Lab/Citation-Integrity/.

Enhancing the coverage of SemRep using a relation classification approach.

OBJECTIVE: Relation extraction is an essential task in the field of biomedical literature mining and offers significant benefits for various downstream applications, including database curation, drug repurposing, and literature-based discovery. The broad-coverage natural language processing (NLP) tool SemRep has established a solid baseline for extracting subject-predicate-object triples from biomedical text and has served as the backbone of the Semantic MEDLINE Database (SemMedDB), a PubMed-scale repository of semantic triples. While SemRep achieves reasonable precision (0.69), its recall is relatively low (0.42). In this study, we aimed to enhance SemRep using a relation classification approach, in order to eventually increase the size and the utility of SemMedDB. METHODS: We combined and extended existing SemRep evaluation datasets to generate training data. We leveraged the pre-trained PubMedBERT model, enhancing it through additional contrastive pre-training and fine-tuning. We experimented with three entity representations: mentions, semantic types, and semantic groups. We evaluated the model performance on a portion of the SemRep Gold Standard dataset and compared it to SemRep performance. We also assessed the effect of the model on a larger set of 12K randomly selected PubMed abstracts. RESULTS: Our results show that the best model yields a precision of 0.62, recall of 0.81, and F1 score of 0.70. Assessment on 12K abstracts shows that the model could double the size of SemMedDB, when applied to entire PubMed. We also manually assessed the quality of 506 triples predicted by the model that SemRep had not previously identified, and found that 67% of these triples were correct. CONCLUSION: These findings underscore the promise of our model in achieving a more comprehensive coverage of relationships mentioned in biomedical literature, thereby showing its potential in enhancing various downstream applications of biomedical literature mining. Data and code related to this study are available at https://github.com/Michelle-Mings/SemRep_RelationClassification.

Automatic categorization of self-acknowledged limitations in randomized controlled trial publications.

OBJECTIVE: Acknowledging study limitations in a scientific publication is a crucial element in scientific transparency and progress. However, limitation reporting is often inadequate. Natural language processing (NLP) methods could support automated reporting checks, improving research transparency. In this study, our objective was to develop a dataset and NLP methods to detect and categorize self-acknowledged limitations (e.g., sample size, blinding) reported in randomized controlled trial (RCT) publications. METHODS: We created a data model of limitation types in RCT studies and annotated a corpus of 200 full-text RCT publications using this data model. We fine-tuned BERT-based sentence classification models to recognize the limitation sentences and their types. To address the small size of the annotated corpus, we experimented with data augmentation approaches, including Easy Data Augmentation (EDA) and Prompt-Based Data Augmentation (PromDA). We applied the best-performing model to a set of about 12K RCT publications to characterize self-acknowledged limitations at larger scale. RESULTS: Our data model consists of 15 categories and 24 sub-categories (e.g., Population and its sub-category DiagnosticCriteria). We annotated 1090 instances of limitation types in 952 sentences (4.8 limitation sentences and 5.5 limitation types per article). A fine-tuned PubMedBERT model for limitation sentence classification improved upon our earlier model by about 1.5 absolute percentage points in F1 score (0.821 vs. 0.8) with statistical significance (p<.001). Our best-performing limitation type classification model, PubMedBERT fine-tuning with PromDA (Output View), achieved an F1 score of 0.7, improving upon the vanilla PubMedBERT model by 2.7 percentage points, with statistical significance (p<.001). CONCLUSION: The model could support automated screening tools which can be used by journals to draw the authors' attention to reporting issues. Automatic extraction of limitations from RCT publications could benefit peer review and evidence synthesis, and support advanced methods to search and aggregate the evidence from the clinical trial literature.

Developing a Knowledge Graph for Pharmacokinetic Natural Product-Drug Interactions.

BACKGROUND: Pharmacokinetic natural product-drug interactions (NPDIs) occur when botanical or other natural products are co-consumed with pharmaceutical drugs. With the growing use of natural products, the risk for potential NPDIs and consequent adverse events has increased. Understanding mechanisms of NPDIs is key to preventing or minimizing adverse events. Although biomedical knowledge graphs (KGs) have been widely used for drug-drug interaction applications, computational investigation of NPDIs is novel. We constructed NP-KG as a first step toward computational discovery of plausible mechanistic explanations for pharmacokinetic NPDIs that can be used to guide scientific research. METHODS: We developed a large-scale, heterogeneous KG with biomedical ontologies, linked data, and full texts of the scientific literature. To construct the KG, biomedical ontologies and drug databases were integrated with the Phenotype Knowledge Translator framework. The semantic relation extraction systems, SemRep and Integrated Network and Dynamic Reasoning Assembler, were used to extract semantic predications (subject-relation-object triples) from full texts of the scientific literature related to the exemplar natural products green tea and kratom. A literature-based graph constructed from the predications was integrated into the ontology-grounded KG to create NP-KG. NP-KG was evaluated with case studies of pharmacokinetic green tea- and kratom-drug interactions through KG path searches and meta-path discovery to determine congruent and contradictory information in NP-KG compared to ground truth data. We also conducted an error analysis to identify knowledge gaps and incorrect predications in the KG. RESULTS: The fully integrated NP-KG consisted of 745,512 nodes and 7,249,576 edges. Evaluation of NP-KG resulted in congruent (38.98% for green tea, 50% for kratom), contradictory (15.25% for green tea, 21.43% for kratom), and both congruent and contradictory (15.25% for green tea, 21.43% for kratom) information compared to ground truth data. Potential pharmacokinetic mechanisms for several purported NPDIs, including the green tea-raloxifene, green tea-nadolol, kratom-midazolam, kratom-quetiapine, and kratom-venlafaxine interactions were congruent with the published literature. CONCLUSION: NP-KG is the first KG to integrate biomedical ontologies with full texts of the scientific literature focused on natural products. We demonstrate the application of NP-KG to identify known pharmacokinetic interactions between natural products and pharmaceutical drugs mediated by drug metabolizing enzymes and transporters. Future work will incorporate context, contradiction analysis, and embedding-based methods to enrich NP-KG. NP-KG is publicly available at https://doi.org/10.5281/zenodo.6814507. The code for relation extraction, KG construction, and hypothesis generation is available at https://github.com/sanyabt/np-kg.

A comment-driven evidence appraisal approach to promoting research findings into practice when only uncertain evidence is available.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Discovering novel drug-supplement interactions using SuppKG generated from the biomedical literature.

OBJECTIVE: Develop a novel methodology to create a comprehensive knowledge graph (SuppKG) to represent a domain with limited coverage in the Unified Medical Language System (UMLS), specifically dietary supplement (DS) information for discovering drug-supplement interactions (DSI), by leveraging biomedical natural language processing (NLP) technologies and a DS domain terminology. MATERIALS AND METHODS: We created SemRepDS (an extension of an NLP tool, SemRep), capable of extracting semantic relations from abstracts by leveraging a DS-specific terminology (iDISK) containing 28,884 DS terms not found in the UMLS. PubMed abstracts were processed using SemRepDS to generate semantic relations, which were then filtered using a PubMedBERT model to remove incorrect relations before generating SuppKG. Two discovery pathways were applied to SuppKG to identify potential DSIs, which are then compared with an existing DSI database and also evaluated by medical professionals for mechanistic plausibility. RESULTS: SemRepDS returned 158.5% more DS entities and 206.9% more DS relations than SemRep. The fine-tuned PubMedBERT model (significantly outperformed other machine learning and BERT models) obtained an F1 score of 0.8605 and removed 43.86% of semantic relations, improving the precision of the relations by 26.4% over pre-filtering. SuppKG consists of 56,635 nodes and 595,222 directed edges with 2,928 DS-specific nodes and 164,738 edges. Manual review of findings identified 182 of 250 (72.8%) proposed DS-Gene-Drug and 77 of 100 (77%) proposed DS-Gene1-Function-Gene2-Drug pathways to be mechanistically plausible. DISCUSSION: With added DS terminology to the UMLS, SemRepDS has the capability to find more DS-specific semantic relationships from PubMed than SemRep. The utility of the resulting SuppKG was demonstrated using discovery patterns to find novel DSIs. CONCLUSION: For the domain with limited coverage in the traditional terminology (e.g., UMLS), we demonstrated an approach to leverage domain terminology and improve existing NLP tools to generate a more comprehensive knowledge graph for the downstream task. Even this study focuses on DSI, the method may be adapted to other domains.

Drug repurposing for COVID-19 via knowledge graph completion.

OBJECTIVE: To discover candidate drugs to repurpose for COVID-19 using literature-derived knowledge and knowledge graph completion methods. METHODS: We propose a novel, integrative, and neural network-based literature-based discovery (LBD) approach to identify drug candidates from PubMed and other COVID-19-focused research literature. Our approach relies on semantic triples extracted using SemRep (via SemMedDB). We identified an informative and accurate subset of semantic triples using filtering rules and an accuracy classifier developed on a BERT variant. We used this subset to construct a knowledge graph, and applied five state-of-the-art, neural knowledge graph completion algorithms (i.e., TransE, RotatE, DistMult, ComplEx, and STELP) to predict drug repurposing candidates. The models were trained and assessed using a time slicing approach and the predicted drugs were compared with a list of drugs reported in the literature and evaluated in clinical trials. These models were complemented by a discovery pattern-based approach. RESULTS: Accuracy classifier based on PubMedBERT achieved the best performance (F1 = 0.854) in identifying accurate semantic predications. Among five knowledge graph completion models, TransE outperformed others (MR = 0.923, Hits@1 = 0.417). Some known drugs linked to COVID-19 in the literature were identified, as well as others that have not yet been studied. Discovery patterns enabled identification of additional candidate drugs and generation of plausible hypotheses regarding the links between the candidate drugs and COVID-19. Among them, five highly ranked and novel drugs (i.e., paclitaxel, SB 203580, alpha 2-antiplasmin, metoclopramide, and oxymatrine) and the mechanistic explanations for their potential use are further discussed. CONCLUSION: We showed that a LBD approach can be feasible not only for discovering drug candidates for COVID-19, but also for generating mechanistic explanations. Our approach can be generalized to other diseases as well as to other clinical questions. Source code and data are available at https://github.com/kilicogluh/lbd-covid.

Toward assessing clinical trial publications for reporting transparency.

OBJECTIVE: To annotate a corpus of randomized controlled trial (RCT) publications with the checklist items of CONSORT reporting guidelines and using the corpus to develop text mining methods for RCT appraisal. METHODS: We annotated a corpus of 50 RCT articles at the sentence level using 37 fine-grained CONSORT checklist items. A subset (31 articles) was double-annotated and adjudicated, while 19 were annotated by a single annotator and reconciled by another. We calculated inter-annotator agreement at the article and section level using MASI (Measuring Agreement on Set-Valued Items) and at the CONSORT item level using Krippendorff's α. We experimented with two rule-based methods (phrase-based and section header-based) and two supervised learning approaches (support vector machine and BioBERT-based neural network classifiers), for recognizing 17 methodology-related items in the RCT Methods sections. RESULTS: We created CONSORT-TM consisting of 10,709 sentences, 4,845 (45%) of which were annotated with 5,246 labels. A median of 28 CONSORT items (out of possible 37) were annotated per article. Agreement was moderate at the article and section levels (average MASI: 0.60 and 0.64, respectively). Agreement varied considerably among individual checklist items (Krippendorff's α= 0.06-0.96). The model based on BioBERT performed best overall for recognizing methodology-related items (micro-precision: 0.82, micro-recall: 0.63, micro-F1: 0.71). Combining models using majority vote and label aggregation further improved precision and recall, respectively. CONCLUSION: Our annotated corpus, CONSORT-TM, contains more fine-grained information than earlier RCT corpora. Low frequency of some CONSORT items made it difficult to train effective text mining models to recognize them. For the items commonly reported, CONSORT-TM can serve as a testbed for text mining methods that assess RCT transparency, rigor, and reliability, and support methods for peer review and authoring assistance. Minor modifications to the annotation scheme and a larger corpus could facilitate improved text mining models. CONSORT-TM is publicly available at https://github.com/kilicogluh/CONSORT-TM.

Broad-coverage biomedical relation extraction with SemRep.

BACKGROUND: 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. RESULTS: A strict evaluation of SemRep on our manually annotated dataset yields 0.55 precision, 0.34 recall, and 0.42 F 1 score. A relaxed evaluation, which more accurately characterizes SemRep performance, yields 0.69 precision, 0.42 recall, and 0.52 F 1 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 1 score. The recall and the F 1 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. CONCLUSIONS: 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.

Biomedical text mining for research rigor and integrity: tasks, challenges, directions.

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.

Towards a characterization of apparent contradictions in the biomedical literature using context analysis.

BACKGROUND: With the substantial growth in the biomedical research literature, a larger number of claims are published daily, some of which seemingly disagree with or contradict prior claims on the same topics. Resolving such contradictions is critical to advancing our understanding of human disease and developing effective treatments. Automated text analysis techniques can facilitate such analysis by extracting claims from the literature, flagging those that are potentially contradictory, and identifying any study characteristics that may explain such contradictions. METHODS: Using SemMedDB, our own PubMed-scale repository of semantic predications (subject-relation-object triples), we identified apparent contradictions in the biomedical research literature and developed a categorization of contextual characteristics that explain such contradictions. Clinically relevant semantic predications relating to 20 diseases and involving opposing predicate pairs (e.g., an intervention treats or causes a disease) were retrieved from SemMedDB. After addressing inference, uncertainty, generic concepts, and NLP errors through automatic and manual filtering steps, a set of apparent contradictions were identified and characterized. RESULTS: We retrieved 117,676 predication instances from 62,360 PubMed abstracts (Jan 1980-Dec 2016). From these instances, automatic filtering steps generated 2236 candidate contradictory pairs. Through manual analysis, we determined that 58 of these pairs (2.6%) were apparent contradictions. We identified five main categories of contextual characteristics that explain these contradictions: (a) internal to the patient, (b) external to the patient, (c) endogenous/exogenous, (d) known controversy, and (e) contradictions in literature. Categories (a) and (b) were subcategorized further (e.g., species, dosage) and accounted for the bulk of the contradictory information. CONCLUSIONS: Semantic predications, by accounting for lexical variability, and SemMedDB, owing to its literature scale, can support identification and elucidation of potentially contradictory claims across the biomedical domain. Further filtering and classification steps are needed to distinguish among them the true contradictory claims. The ability to detect contradictions automatically can facilitate important biomedical knowledge management tasks, such as tracking and verifying scientific claims, summarizing research on a given topic, identifying knowledge gaps, and assessing evidence for systematic reviews, with potential benefits to the scientific community. Future work will focus on automating these steps for fully automatic recognition of contradictions from the biomedical research literature.

Confirm or refute?: A comparative study on citation sentiment classification in clinical research publications.

Quantifying scientific impact of researchers and journals relies largely on citation counts, despite the acknowledged limitations of this approach. The need for more suitable alternatives has prompted research into developing advanced metrics, such as h-index and Relative Citation Ratio (RCR), as well as better citation categorization schemes to capture the various functions that citations serve in a publication. One such scheme involves citation sentiment: whether a reference paper is cited positively (agreement with the findings of the reference paper), negatively (disagreement), or neutrally. The ability to classify citation function in this manner can be viewed as a first step toward a more fine-grained bibliometrics. In this study, we compared several approaches, varying in complexity, for classification of citation sentiment in clinical trial publications. Using a corpus of 285 discussion sections from as many publications (a total of 4,182 citations), we developed a rule-based method as well as supervised machine learning models based on support vector machines (SVM) and two variants of deep neural networks; namely, convolutional neural network (CNN) and bidirectional long short-term memory (BiLSTM). A CNN model augmented with hand-crafted features yielded the best performance (0.882 accuracy and 0.721 macro-F1 on held-out set). Our results show that baseline performances of traditional supervised learning algorithms and deep neural network architectures are similar and that hand-crafted features based on sentiment dictionaries and rhetorical structure allow neural network approaches to outperform traditional machine learning approaches for this task. We make the rule-based method and the best-performing neural network model publicly available at: https://github.com/kilicogluh/clinical-citation-sentiment.

Semantic annotation of consumer health questions.

BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.

Sortal anaphora resolution to enhance relation extraction from biomedical literature.

BACKGROUND: Entity coreference is common in biomedical literature and it can affect text understanding systems that rely on accurate identification of named entities, such as relation extraction and automatic summarization. Coreference resolution is a foundational yet challenging natural language processing task which, if performed successfully, is likely to enhance such systems significantly. In this paper, we propose a semantically oriented, rule-based method to resolve sortal anaphora, a specific type of coreference that forms the majority of coreference instances in biomedical literature. The method addresses all entity types and relies on linguistic components of SemRep, a broad-coverage biomedical relation extraction system. It has been incorporated into SemRep, extending its core semantic interpretation capability from sentence level to discourse level. RESULTS: We evaluated our sortal anaphora resolution method in several ways. The first evaluation specifically focused on sortal anaphora relations. Our methodology achieved a F1 score of 59.6 on the test portion of a manually annotated corpus of 320 Medline abstracts, a 4-fold improvement over the baseline method. Investigating the impact of sortal anaphora resolution on relation extraction, we found that the overall effect was positive, with 50 % of the changes involving uninformative relations being replaced by more specific and informative ones, while 35 % of the changes had no effect, and only 15 % were negative. We estimate that anaphora resolution results in changes in about 1.5 % of approximately 82 million semantic relations extracted from the entire PubMed. CONCLUSIONS: Our results demonstrate that a heavily semantic approach to sortal anaphora resolution is largely effective for biomedical literature. Our evaluation and error analysis highlight some areas for further improvements, such as coordination processing and intra-sentential antecedent selection.

Augmenting microarray data with literature-based knowledge to enhance gene regulatory network inference.

Gene regulatory networks are a crucial aspect of systems biology in describing molecular mechanisms of the cell. Various computational models rely on random gene selection to infer such networks from microarray data. While incorporation of prior knowledge into data analysis has been deemed important, in practice, it has generally been limited to referencing genes in probe sets and using curated knowledge bases. We investigate the impact of augmenting microarray data with semantic relations automatically extracted from the literature, with the view that relations encoding gene/protein interactions eliminate the need for random selection of components in non-exhaustive approaches, producing a more accurate model of cellular behavior. A genetic algorithm is then used to optimize the strength of interactions using microarray data and an artificial neural network fitness function. The result is a directed and weighted network providing the individual contribution of each gene to its target. For testing, we used invasive ductile carcinoma of the breast to query the literature and a microarray set containing gene expression changes in these cells over several time points. Our model demonstrates significantly better fitness than the state-of-the-art model, which relies on an initial random selection of genes. Comparison to the component pathways of the KEGG Pathways in Cancer map reveals that the resulting networks contain both known and novel relationships. The p53 pathway results were manually validated in the literature. 60% of non-KEGG relationships were supported (74% for highly weighted interactions). The method was then applied to yeast data and our model again outperformed the comparison model. Our results demonstrate the advantage of combining gene interactions extracted from the literature in the form of semantic relations with microarray analysis in generating contribution-weighted gene regulatory networks. This methodology can make a significant contribution to understanding the complex interactions involved in cellular behavior and molecular physiology.

The role of fine-grained annotations in supervised recognition of risk factors for heart disease from EHRs.

This paper describes a supervised machine learning approach for identifying heart disease risk factors in clinical text, and assessing the impact of annotation granularity and quality on the system's ability to recognize these risk factors. We utilize a series of support vector machine models in conjunction with manually built lexicons to classify triggers specific to each risk factor. The features used for classification were quite simple, utilizing only lexical information and ignoring higher-level linguistic information such as syntax and semantics. Instead, we incorporated high-quality data to train the models by annotating additional information on top of a standard corpus. Despite the relative simplicity of the system, it achieves the highest scores (micro- and macro-F1, and micro- and macro-recall) out of the 20 participants in the 2014 i2b2/UTHealth Shared Task. This system obtains a micro- (macro-) precision of 0.8951 (0.8965), recall of 0.9625 (0.9611), and F1-measure of 0.9276 (0.9277). Additionally, we perform a series of experiments to assess the value of the annotated data we created. These experiments show how manually-labeled negative annotations can improve information extraction performance, demonstrating the importance of high-quality, fine-grained natural language annotations.

Using semantic predications to uncover drug-drug interactions in clinical data.

In this study we report on potential drug-drug interactions between drugs occurring in patient clinical data. Results are based on relationships in SemMedDB, a database of structured knowledge extracted from all MEDLINE citations (titles and abstracts) using SemRep. The core of our methodology is to construct two potential drug-drug interaction schemas, based on relationships extracted from SemMedDB. In the first schema, Drug1 and Drug2 interact through Drug1's effect on some gene, which in turn affects Drug2. In the second, Drug1 affects Gene1, while Drug2 affects Gene2. Gene1 and Gene2, together, then have an effect on some biological function. After checking each drug pair from the medication lists of each of 22 patients, we found 19 known and 62 unknown drug-drug interactions using both schemas. For example, our results suggest that the interaction of Lisinopril, an ACE inhibitor commonly prescribed for hypertension, and the antidepressant sertraline can potentially increase the likelihood and possibly the severity of psoriasis. We also assessed the relationships extracted by SemRep from a linguistic perspective and found that the precision of SemRep was 0.58 for 300 randomly selected sentences from MEDLINE. Our study demonstrates that the use of structured knowledge in the form of relationships from the biomedical literature can support the discovery of potential drug-drug interactions occurring in patient clinical data. Moreover, SemMedDB provides a good knowledge resource for expanding the range of drugs, genes, and biological functions considered as elements in various drug-drug interaction pathways.

CONSORT-TM: Text classification models for assessing the completeness of randomized controlled trial publications.

Objective: To develop text classification models for determining whether the checklist items in the CONSORT reporting guidelines are reported in randomized controlled trial publications. Materials and Methods: Using a corpus annotated at the sentence level with 37 fine-grained CONSORT items, we trained several sentence classification models (PubMedBERT fine-tuning, BioGPT fine-tuning, and in-context learning with GPT-4) and compared their performance. To address the problem of small training dataset, we used several data augmentation methods (EDA, UMLS-EDA, text generation and rephrasing with GPT-4) and assessed their impact on the fine-tuned PubMedBERT model. We also fine-tuned PubMedBERT models limited to checklist items associated with specific sections (e.g., Methods) to evaluate whether such models could improve performance compared to the single full model. We performed 5-fold cross-validation and report precision, recall, F1 score, and area under curve (AUC). Results: Fine-tuned PubMedBERT model that takes as input the sentence and the surrounding sentence representations and uses section headers yielded the best overall performance (0.71 micro-F1, 0.64 macro-F1). Data augmentation had limited positive effect, UMLS-EDA yielding slightly better results than data augmentation using GPT-4. BioGPT fine-tuning and GPT-4 in-context learning exhibited suboptimal results. Methods-specific model yielded higher performance for methodology items, other section-specific models did not have significant impact. Conclusion: Most CONSORT checklist items can be recognized reasonably well with the fine-tuned PubMedBERT model but there is room for improvement. Improved models can underpin the journal editorial workflows and CONSORT adherence checks and can help authors in improving the reporting quality and completeness of their manuscripts.