Large Language Models for Social Determinants of Health Information Extraction from Clinical Notes - A Generalizable Approach across Institutions.

The consistent and persuasive evidence illustrating the influence of social determinants on health has prompted a growing realization throughout the health care sector that enhancing health and health equity will likely depend, at least to some extent, on addressing detrimental social determinants. However, detailed social determinants of health (SDoH) information is often buried within clinical narrative text in electronic health records (EHRs), necessitating natural language processing (NLP) methods to automatically extract these details. Most current NLP efforts for SDoH extraction have been limited, investigating on limited types of SDoH elements, deriving data from a single institution, focusing on specific patient cohorts or note types, with reduced focus on generalizability. This study aims to address these issues by creating cross-institutional corpora spanning different note types and healthcare systems, and developing and evaluating the generalizability of classification models, including novel large language models (LLMs), for detecting SDoH factors from diverse types of notes from four institutions: Harris County Psychiatric Center, University of Texas Physician Practice, Beth Israel Deaconess Medical Center, and Mayo Clinic. Four corpora of deidentified clinical notes were annotated with 21 SDoH factors at two levels: level 1 with SDoH factor types only and level 2 with SDoH factors along with associated values. Three traditional classification algorithms (XGBoost, TextCNN, Sentence BERT) and an instruction tuned LLM-based approach (LLaMA) were developed to identify multiple SDoH factors. Substantial variation was noted in SDoH documentation practices and label distributions based on patient cohorts, note types, and hospitals. The LLM achieved top performance with micro-averaged F1 scores over 0.9 on level 1 annotated corpora and an F1 over 0.84 on level 2 annotated corpora. While models performed well when trained and tested on individual datasets, cross-dataset generalization highlighted remaining obstacles. To foster collaboration, access to partial annotated corpora and models trained by merging all annotated datasets will be made available on the PhysioNet repository.

Me-LLaMA: Foundation Large Language Models for Medical Applications.

Recent advancements in large language models (LLMs) such as ChatGPT and LLaMA have hinted at their potential to revolutionize medical applications, yet their application in clinical settings often reveals limitations due to a lack of specialized training on medical-specific data. In response to this challenge, this study introduces Me-LLaMA, a novel 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 methodology leverages a comprehensive domain-specific data suite, including 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 critical medical 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. With task-specific instruction tuning, Me-LLaMA models outperform ChatGPT on 7 out of 8 datasets and GPT-4 on 5 out of 8 datasets. 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.

A Study of Biomedical Relation Extraction Using GPT Models.

Relation Extraction (RE) is a natural language processing (NLP) task for extracting semantic relations between biomedical entities. Recent developments in pre-trained large language models (LLM) motivated NLP researchers to use them for various NLP tasks. We investigated GPT-3.5-turbo and GPT-4 on extracting the relations from three standard datasets, EU-ADR, Gene Associations Database (GAD), and ChemProt. Unlike the existing approaches using datasets with masked entities, we used three versions for each dataset for our experiment: a version with masked entities, a second version with the original entities (unmasked), and a third version with abbreviations replaced with the original terms. We developed the prompts for various versions and used the chat completion model from GPT API. Our approach achieved a F1-score of 0.498 to 0.809 for GPT-3.5-turbo, and a highest F1-score of 0.84 for GPT-4. For certain experiments, the performance of GPT, BioBERT, and PubMedBERT are almost the same.

Ensemble pretrained language models to extract biomedical knowledge from literature.

OBJECTIVES: The rapid expansion of biomedical literature necessitates automated techniques to discern relationships between biomedical concepts from extensive free text. Such techniques facilitate the development of detailed knowledge bases and highlight research deficiencies. The LitCoin Natural Language Processing (NLP) challenge, organized by the National Center for Advancing Translational Science, aims to evaluate such potential and provides a manually annotated corpus for methodology development and benchmarking. MATERIALS AND METHODS: For the named entity recognition (NER) task, we utilized ensemble learning to merge predictions from three domain-specific models, namely BioBERT, PubMedBERT, and BioM-ELECTRA, devised a rule-driven detection method for cell line and taxonomy names and annotated 70 more abstracts as additional corpus. We further finetuned the T0pp model, with 11 billion parameters, to boost the performance on relation extraction and leveraged entites' location information (eg, title, background) to enhance novelty prediction performance in relation extraction (RE). RESULTS: Our pioneering NLP system designed for this challenge secured first place in Phase I-NER and second place in Phase II-relation extraction and novelty prediction, outpacing over 200 teams. We tested OpenAI ChatGPT 3.5 and ChatGPT 4 in a Zero-Shot setting using the same test set, revealing that our finetuned model considerably surpasses these broad-spectrum large language models. DISCUSSION AND CONCLUSION: Our outcomes depict a robust NLP system excelling in NER and RE across various biomedical entities, emphasizing that task-specific models remain superior to generic large ones. Such insights are valuable for endeavors like knowledge graph development and hypothesis formulation in biomedical research.

Advancing entity recognition in biomedicine via instruction tuning of large language models.

MOTIVATION: Large Language Models (LLMs) have the potential to revolutionize the field of Natural Language Processing, excelling not only in text generation and reasoning tasks but also in their ability for zero/few-shot learning, swiftly adapting to new tasks with minimal fine-tuning. LLMs have also demonstrated great promise in biomedical and healthcare applications. However, when it comes to Named Entity Recognition (NER), particularly within the biomedical domain, LLMs fall short of the effectiveness exhibited by fine-tuned domain-specific models. One key reason is that NER is typically conceptualized as a sequence labeling task, whereas LLMs are optimized for text generation and reasoning tasks. RESULTS: We developed an instruction-based learning paradigm that transforms biomedical NER from a sequence labeling task into a generation task. This paradigm is end-to-end and streamlines the training and evaluation process by automatically repurposing pre-existing biomedical NER datasets. We further developed BioNER-LLaMA using the proposed paradigm with LLaMA-7B as the foundational LLM. We conducted extensive testing on BioNER-LLaMA across three widely recognized biomedical NER datasets, consisting of entities related to diseases, chemicals, and genes. The results revealed that BioNER-LLaMA consistently achieved higher F1-scores ranging from 5% to 30% compared to the few-shot learning capabilities of GPT-4 on datasets with different biomedical entities. We show that a general-domain LLM can match the performance of rigorously fine-tuned PubMedBERT models and PMC-LLaMA, biomedical-specific language model. Our findings underscore the potential of our proposed paradigm in developing general-domain LLMs that can rival SOTA performances in multi-task, multi-domain scenarios in biomedical and health applications. AVAILABILITY AND IMPLEMENTATION: Datasets and other resources are available at https://github.com/BIDS-Xu-Lab/BioNER-LLaMA.

FedFSA: Hybrid and federated framework for functional status ascertainment across institutions.

INTRODUCTION: Patients' functional status assesses their independence in performing activities of daily living, including basic ADLs (bADL), and more complex instrumental activities (iADL). Existing studies have discovered that patients' functional status is a strong predictor of health outcomes, particularly in older adults. Depite their usefulness, much of the functional status information is stored in electronic health records (EHRs) in either semi-structured or free text formats. This indicates the pressing need to leverage computational approaches such as natural language processing (NLP) to accelerate the curation of functional status information. In this study, we introduced FedFSA, a hybrid and federated NLP framework designed to extract functional status information from EHRs across multiple healthcare institutions. METHODS: FedFSA consists of four major components: 1) individual sites (clients) with their private local data, 2) a rule-based information extraction (IE) framework for ADL extraction, 3) a BERT model for functional status impairment classification, and 4) a concept normalizer. The framework was implemented using the OHNLP Backbone for rule-based IE and open-source Flower and PyTorch library for federated BERT components. For gold standard data generation, we carried out corpus annotation to identify functional status-related expressions based on ICF definitions. Four healthcare institutions were included in the study. To assess FedFSA, we evaluated the performance of category- and institution-specific ADL extraction across different experimental designs. RESULTS: ADL extraction performance ranges from an F1-score of 0.907 to 0.986 for bADL and 0.825 to 0.951 for iADL across the four healthcare sites. The performance for ADL extraction with impairment ranges from an F1-score of 0.722 to 0.954 for bADL and 0.674 to 0.813 for iADL across four healthcare sites. For category-specific ADL extraction, laundry and transferring yielded relatively high performance, while dressing, medication, bathing, and continence achieved moderate-high performance. Conversely, food preparation and toileting showed low performance. CONCLUSION: NLP performance varied across ADL categories and healthcare sites. Federated learning using a FedFSA framework performed higher than non-federated learning for impaired ADL extraction at all healthcare sites. Our study demonstrated the potential of the federated learning framework in functional status extraction and impairment classification in EHRs, exemplifying the importance of a large-scale, multi-institutional collaborative development effort.

Improving large language models for clinical named entity recognition via prompt engineering.

IMPORTANCE: The study highlights the potential of large language models, specifically GPT-3.5 and GPT-4, in processing complex clinical data and extracting meaningful information with minimal training data. By developing and refining prompt-based strategies, we can significantly enhance the models' performance, making them viable tools for clinical NER tasks and possibly reducing the reliance on extensive annotated datasets. OBJECTIVES: This study quantifies the capabilities of GPT-3.5 and GPT-4 for clinical named entity recognition (NER) tasks and proposes task-specific prompts to improve their performance. MATERIALS AND METHODS: We evaluated these models on 2 clinical NER tasks: (1) to extract medical problems, treatments, and tests from clinical notes in the MTSamples corpus, following the 2010 i2b2 concept extraction shared task, and (2) to identify nervous system disorder-related adverse events from safety reports in the vaccine adverse event reporting system (VAERS). To improve the GPT models' performance, we developed a clinical task-specific prompt framework that includes (1) baseline prompts with task description and format specification, (2) annotation guideline-based prompts, (3) error analysis-based instructions, and (4) annotated samples for few-shot learning. We assessed each prompt's effectiveness and compared the models to BioClinicalBERT. RESULTS: Using baseline prompts, GPT-3.5 and GPT-4 achieved relaxed F1 scores of 0.634, 0.804 for MTSamples and 0.301, 0.593 for VAERS. Additional prompt components consistently improved model performance. When all 4 components were used, GPT-3.5 and GPT-4 achieved relaxed F1 socres of 0.794, 0.861 for MTSamples and 0.676, 0.736 for VAERS, demonstrating the effectiveness of our prompt framework. Although these results trail BioClinicalBERT (F1 of 0.901 for the MTSamples dataset and 0.802 for the VAERS), it is very promising considering few training samples are needed. DISCUSSION: The study's findings suggest a promising direction in leveraging LLMs for clinical NER tasks. However, while the performance of GPT models improved with task-specific prompts, there's a need for further development and refinement. LLMs like GPT-4 show potential in achieving close performance to state-of-the-art models like BioClinicalBERT, but they still require careful prompt engineering and understanding of task-specific knowledge. The study also underscores the importance of evaluation schemas that accurately reflect the capabilities and performance of LLMs in clinical settings. CONCLUSION: While direct application of GPT models to clinical NER tasks falls short of optimal performance, our task-specific prompt framework, incorporating medical knowledge and training samples, significantly enhances GPT models' feasibility for potential clinical applications.

Towards precise PICO extraction from abstracts of randomized controlled trials using a section-specific learning approach.

MOTIVATION: Automated extraction of participants, intervention, comparison/control, and outcome (PICO) from the randomized controlled trial (RCT) abstracts is important for evidence synthesis. Previous studies have demonstrated the feasibility of applying natural language processing (NLP) for PICO extraction. However, the performance is not optimal due to the complexity of PICO information in RCT abstracts and the challenges involved in their annotation. RESULTS: We propose a two-step NLP pipeline to extract PICO elements from RCT abstracts: (i) sentence classification using a prompt-based learning model and (ii) PICO extraction using a named entity recognition (NER) model. First, the sentences in abstracts were categorized into four sections namely background, methods, results, and conclusions. Next, the NER model was applied to extract the PICO elements from the sentences within the title and methods sections that include >96% of PICO information. We evaluated our proposed NLP pipeline on three datasets, the EBM-NLPmoddataset, a randomly selected and reannotated dataset of 500 RCT abstracts from the EBM-NLP corpus, a dataset of 150 COVID-19 RCT abstracts, and a dataset of 150 Alzheimer's disease (AD) RCT abstracts. The end-to-end evaluation reveals that our proposed approach achieved an overall micro F1 score of 0.833 on the EBM-NLPmod dataset, 0.928 on the COVID-19 dataset, and 0.899 on the AD dataset when measured at the token-level and an overall micro F1 score of 0.712 on EBM-NLPmod dataset, 0.850 on the COVID-19 dataset, and 0.805 on the AD dataset when measured at the entity-level. AVAILABILITY: Our codes and datasets are publicly available at https://github.com/BIDS-Xu-Lab/section_specific_annotation_of_PICO. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Systematic design and data-driven evaluation of social determinants of health ontology (SDoHO).

OBJECTIVE: Social determinants of health (SDoH) play critical roles in health outcomes and well-being. Understanding the interplay of SDoH and health outcomes is critical to reducing healthcare inequalities and transforming a "sick care" system into a "health-promoting" system. To address the SDOH terminology gap and better embed relevant elements in advanced biomedical informatics, we propose an SDoH ontology (SDoHO), which represents fundamental SDoH factors and their relationships in a standardized and measurable way. MATERIAL AND METHODS: Drawing on the content of existing ontologies relevant to certain aspects of SDoH, we used a top-down approach to formally model classes, relationships, and constraints based on multiple SDoH-related resources. Expert review and coverage evaluation, using a bottom-up approach employing clinical notes data and a national survey, were performed. RESULTS: We constructed the SDoHO with 708 classes, 106 object properties, and 20 data properties, with 1,561 logical axioms and 976 declaration axioms in the current version. Three experts achieved 0.967 agreement in the semantic evaluation of the ontology. A comparison between the coverage of the ontology and SDOH concepts in 2 sets of clinical notes and a national survey instrument also showed satisfactory results. DISCUSSION: SDoHO could potentially play an essential role in providing a foundation for a comprehensive understanding of the associations between SDoH and health outcomes and paving the way for health equity across populations. CONCLUSION: SDoHO has well-designed hierarchies, practical objective properties, and versatile functionalities, and the comprehensive semantic and coverage evaluation achieved promising performance compared to the existing ontologies relevant to SDoH.

Representing and utilizing clinical textual data for real world studies: An OHDSI approach.

Clinical documentation in electronic health records contains crucial narratives and details about patients and their care. Natural language processing (NLP) can unlock the information conveyed in clinical notes and reports, and thus plays a critical role in real-world studies. The NLP Working Group at the Observational Health Data Sciences and Informatics (OHDSI) consortium was established to develop methods and tools to promote the use of textual data and NLP in real-world observational studies. In this paper, we describe a framework for representing and utilizing textual data in real-world evidence generation, including representations of information from clinical text in the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM), the workflow and tools that were developed to extract, transform and load (ETL) data from clinical notes into tables in OMOP CDM, as well as current applications and specific use cases of the proposed OHDSI NLP solution at large consortia and individual institutions with English textual data. Challenges faced and lessons learned during the process are also discussed to provide valuable insights for researchers who are planning to implement NLP solutions in real-world studies.

Mining of EHR for interface terminology concepts for annotating EHRs of COVID patients.

BACKGROUND: Two years into the COVID-19 pandemic and with more than five million deaths worldwide, the healthcare establishment continues to struggle with every new wave of the pandemic resulting from a new coronavirus variant. Research has demonstrated that there are variations in the symptoms, and even in the order of symptom presentations, in COVID-19 patients infected by different SARS-CoV-2 variants (e.g., Alpha and Omicron). Textual data in the form of admission notes and physician notes in the Electronic Health Records (EHRs) is rich in information regarding the symptoms and their orders of presentation. Unstructured EHR data is often underutilized in research due to the lack of annotations that enable automatic extraction of useful information from the available extensive volumes of textual data. METHODS: We present the design of a COVID Interface Terminology (CIT), not just a generic COVID-19 terminology, but one serving a specific purpose of enabling automatic annotation of EHRs of COVID-19 patients. CIT was constructed by integrating existing COVID-related ontologies and mining additional fine granularity concepts from clinical notes. The iterative mining approach utilized the techniques of 'anchoring' and 'concatenation' to identify potential fine granularity concepts to be added to the CIT. We also tested the generalizability of our approach on a hold-out dataset and compared the annotation coverage to the coverage obtained for the dataset used to build the CIT. RESULTS: Our experiments demonstrate that this approach results in higher annotation coverage compared to existing ontologies such as SNOMED CT and Coronavirus Infectious Disease Ontology (CIDO). The final version of CIT achieved about 20% more coverage than SNOMED CT and 50% more coverage than CIDO. In the future, the concepts mined and added into CIT could be used as training data for machine learning models for mining even more concepts into CIT and further increasing the annotation coverage. CONCLUSION: In this paper, we demonstrated the construction of a COVID interface terminology that can be utilized for automatically annotating EHRs of COVID-19 patients. The techniques presented can identify frequently documented fine granularity concepts that are missing in other ontologies thereby increasing the annotation coverage.

Integrating Commercial and Social Determinants of Health: A Unified Ontology for Non-Clinical Determinants of Health.

The pivotal impact of Social Determinants of Health (SDoH) on people's health and well-being has been widely recognized and researched. However, the effect of Commercial Determinants of Health (CDoH) is only now garnering increased attention. Developing an ontology for CDoH can offer a systematic approach to identifying and categorizing the diverse commercial factors affecting health. These factors, including the production, distribution, and marketing of goods and services, may exert a substantial influence on health outcomes. The objectives of this research are 1) to develop an ontology for CDoH by utilizing PubMed articles and ChatGPT; 2) to foster ontology reuse by integrating CDoH with an existing SDoH ontology into a unified structure; 3) to devise an overarching conception for all nonclinical determinants of health (N-CDoH) and to create an initial ontology for N-CDoH; 4) and to validate the degree of correspondence between concepts provided by ChatGPT with the existing SDoH ontology.

Visual comprehension and orientation into the COVID-19 CIDO ontology.

The current intensive research on potential remedies and vaccinations for COVID-19 would greatly benefit from an ontology of standardized COVID terms. The Coronavirus Infectious Disease Ontology (CIDO) is the largest among several COVID ontologies, and it keeps growing, but it is still a medium sized ontology. Sophisticated CIDO users, who need more than searching for a specific concept, require orientation and comprehension of CIDO. In previous research, we designed a summarization network called "partial-area taxonomy" to support comprehension of ontologies. The partial-area taxonomy for CIDO is of smaller magnitude than CIDO, but is still too large for comprehension. We present here the "weighted aggregate taxonomy" of CIDO, designed to provide compact views at various granularities of our partial-area taxonomy (and the CIDO ontology). Such a compact view provides a "big picture" of the content of an ontology. In previous work, in the visualization patterns used for partial-area taxonomies, the nodes were arranged in levels according to the numbers of relationships of their concepts. Applying this visualization pattern to CIDO's weighted aggregate taxonomy resulted in an overly long and narrow layout that does not support orientation and comprehension since the names of nodes are barely readable. Thus, we introduce in this paper an innovative visualization of the weighted aggregate taxonomy for better orientation and comprehension of CIDO (and other ontologies). A measure for the efficiency of a layout is introduced and is used to demonstrate the advantage of the new layout over the previous one. With this new visualization, the user can "see the forest for the trees" of the ontology. Benefits of this visualization in highlighting insights into CIDO's content are provided. Generality of the new layout is demonstrated.

Extending import detection algorithms for concept import from two to three biomedical terminologies.

BACKGROUND: While enrichment of terminologies can be achieved in different ways, filling gaps in the IS-A hierarchy backbone of a terminology appears especially promising. To avoid difficult manual inspection, we started a research program in 2014, investigating terminology densities, where the comparison of terminologies leads to the algorithmic discovery of potentially missing concepts in a target terminology. While candidate concepts have to be approved for import by an expert, the human effort is greatly reduced by algorithmic generation of candidates. In previous studies, a single source terminology was used with one target terminology. METHODS: In this paper, we are extending the algorithmic detection of "candidate concepts for import" from one source terminology to two source terminologies used in tandem. We show that the combination of two source terminologies relative to one target terminology leads to the discovery of candidate concepts for import that could not be found with the same "reliability" when comparing one source terminology alone to the target terminology. We investigate which triples of UMLS terminologies can be gainfully used for the described purpose and how many candidate concepts can be found for each individual triple of terminologies. RESULTS: The analysis revealed a specific configuration of concepts, overlapping two source and one target terminology, for which we coined the name "fire ladder" pattern. The three terminologies in this pattern are tied together by a kind of "transitivity." We provide a quantitative analysis of the discovered fire ladder patterns and we report on the inter-rater agreement concerning the decision of importing candidate concepts from source terminologies into the target terminology. We algorithmically identified 55 instances of the fire ladder pattern and two domain experts agreed on import for 39 instances. In total, 48 concepts were approved by at least one expert. In addition, 105 import candidate concepts from a single source terminology into the target terminology were also detected, as a "beneficial side-effect" of this method, increasing the cardinality of the result. CONCLUSION: We showed that pairs of biomedical source terminologies can be transitively chained to suggest possible imports of concepts into a target terminology.

Outlier concepts auditing methodology for a large family of biomedical ontologies.

BACKGROUND: Summarization networks are compact summaries of ontologies. The "Big Picture" view offered by summarization networks enables to identify sets of concepts that are more likely to have errors than control concepts. For ontologies that have outgoing lateral relationships, we have developed the "partial-area taxonomy" summarization network. Prior research has identified one kind of outlier concepts, concepts of small partials-areas within partial-area taxonomies. Previously we have shown that the small partial-area technique works successfully for four ontologies (or their hierarchies). METHODS: To improve the Quality Assurance (QA) scalability, a family-based QA framework, where one QA technique is potentially applicable to a whole family of ontologies with similar structural features, was developed. The 373 ontologies hosted at the NCBO BioPortal in 2015 were classified into a collection of families based on structural features. A meta-ontology represents this family collection, including one family of ontologies having outgoing lateral relationships. The process of updating the current meta-ontology is described. To conclude that one QA technique is applicable for at least half of the members for a family F, this technique should be demonstrated as successful for six out of six ontologies in F. We describe a hypothesis setting the condition required for a technique to be successful for a given ontology. The process of a study to demonstrate such success is described. This paper intends to prove the scalability of the small partial-area technique. RESULTS: We first updated the meta-ontology classifying 566 BioPortal ontologies. There were 371 ontologies in the family with outgoing lateral relationships. We demonstrated the success of the small partial-area technique for two ontology hierarchies which belong to this family, SNOMED CT's Specimen hierarchy and NCIt's Gene hierarchy. Together with the four previous ontologies from the same family, we fulfilled the "six out of six" condition required to show the scalability for the whole family. CONCLUSIONS: We have shown that the small partial-area technique can be potentially successful for the family of ontologies with outgoing lateral relationships in BioPortal, thus improve the scalability of this QA technique.

A review of auditing techniques for the Unified Medical Language System.

OBJECTIVE: The study sought to describe the literature related to the development of methods for auditing the Unified Medical Language System (UMLS), with particular attention to identifying errors and inconsistencies of attributes of the concepts in the UMLS Metathesaurus. MATERIALS AND METHODS: We applied the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) approach by searching the MEDLINE database and Google Scholar for studies referencing the UMLS and any of several terms related to auditing, error detection, and quality assurance. A qualitative analysis and summarization of articles that met inclusion criteria were performed. RESULTS: Eighty-three studies were reviewed in detail. We first categorized techniques based on various aspects including concepts, concept names, and synonymy (n = 37), semantic type assignments (n = 36), hierarchical relationships (n = 24), lateral relationships (n = 12), ontology enrichment (n = 8), and ontology alignment (n = 18). We also categorized the methods according to their level of automation (ie, automated systematic, automated heuristic, or manual) and the type of knowledge used (ie, intrinsic or extrinsic knowledge). CONCLUSIONS: This study is a comprehensive review of the published methods for auditing the various conceptual aspects of the UMLS. Categorizing the auditing techniques according to the various aspects will enable the curators of the UMLS as well as researchers comprehensive easy access to this wealth of knowledge (eg, for auditing lateral relationships in the UMLS). We also reviewed ontology enrichment and alignment techniques due to their critical use of and impact on the UMLS.

Alternative classification of identical concepts in different terminologies: Different ways to view the world.

In previous research, we have studied concepts that occur in pairs of medical terminologies and are known to be identical, because they have the same ID number in the Unified Medical Language System (UMLS). We observed that such concepts rarely have exactly the same sets of children (=subconcepts) in the two terminologies. The number of common children was found to vary widely. A special situation was identified where the children in one terminology relate to the common parent in a very different way than the children in the other terminology. For example, children in one terminology might subdivide a parent concept by anatomical location in one terminology and by disease kind in the other terminology. We coined the term "alternative classification" (of the same parent concept) for such situations. In previous work, only human experts could recognize alternative classifications. In this paper, we present a mathematically expressed criterion for likely cases of alternative classifications. We compare the recommendations of this criterion, expressed by a mathematical quantity called "EFI" becoming zero, with the decisions of a human expert. It is found that the human expert agreed with the criterion in 72% of all cases, which is a big improvement over having no computable criterion at all. Besides alternative classifications, common parent concepts in a pair of terminologies might also indicate a possible import of a child concept missing in one terminology, different granularities, or errors in either one of the two terminologies. In this paper, we further investigate different kinds of alternative classifications.

How Sustainable are Biomedical Ontologies?

BioPortal is widely regarded to be the world's most comprehensive repository of biomedical ontologies. With a coverage of many biomedical subfields by 716 ontologies (June 27, 2018), BioPortal is an extremely diverse repository. BioPortal maintains easily accessible information about the ontologies submitted by ontology curators. This includes size (concepts/classes, relationships/properties), number of projects, update history, and access history. Ontologies vary by size (from a few concepts to hundreds of thousands), by frequency of update/visit and by number of projects. Interestingly, some ontologies are rarely updated even though they contain thousands of concepts. In an informal email inquiry, we attempted to understand the reasons why ontologies that were built with a major investment of effort are apparently not sustained. Our analysis indicates that lack of funding, unavailability of human resources, and folding of ontologies into other ontologies are the most common among several other factors for discontinued maintenance of these ontologies.

Leveraging Horizontal Density Differences between Ontologies to Identify Missing Child Concepts: A Proof of Concept.

Previously, we investigated pairs of ontologies with local similarities where corresponding "is-a" paths are of different lengths. This indicated the possibility of importing concepts from one ontology into the other. We referred to such structures as diamonds of concepts. In this paper, we address the question whether pairs of identical concepts in pairs of ontologies have the same children in both. Separate reviews of SNOMED CT and NCIt relative to eight other ontologies uncovered differences in child sets. We provide quantitative data concerning these differences. In cases where there are many identical children in two ontologies, the questions arise why one has more children and whether these children are "missing" in the other ontology. We performed randomized controlled trials in which a human expert evaluated the "fit for import" of such potentially missing child concepts. In two out of four studies, statistical significance was achieved in support of algorithmic import.

Extended Analysis of Topological-Pattern-Based Ontology Enrichment.

Maintenance of biomedical ontologies is difficult. We have previously developed a topological-pattern-based method to deal with the problem of identifying concepts in a reference ontology that could be of interest for insertion into a target ontology. Assuming that both ontologies are parts of the Unified Medical Language System (UMLS), the method suggests approximate locations where the target ontology could be extended with new concepts from the reference ontology. However, the final decision about each concept has to be made by a human expert. In this paper, we describe the universe of cross-ontology topological patterns in quantitative terms. We then present a theoretical analysis of the number of potential placements of reference concepts in a path in a target ontology, allowing for new cross-ontology synonyms. This provides a rough estimate of what expert resources need to be allocated for the task. One insight in previous work on this topic was the large percentage of cases where importing concepts was impossible, due to a configuration called "alternative classification." In this paper, we confirm this observation. Our target ontology is the National Cancer Institute thesaurus (NCIt). However, the methods can be applied to other pairs of ontologies with hierarchical relationships from the UMLS.