Query-Constraint-Based Mining of Association Rules for Exploratory Analysis of Clinical Datasets in the National Sleep Research Resource

Background: Association Rule Mining (ARM) has been widely used by biomedical researchers to perform exploratory data analysis and uncover potential relationships among variables in biomedical datasets. However, when biomedical datasets are high-dimensional, performing ARM on such datasets will yield a large number of rules, many of which may be uninteresting. Especially for imbalanced datasets, performing ARM directly would result in uninteresting rules that are dominated by certain variables that capture general characteristics. Methods: We introduce a query-constraint-based ARM (QARM) approach for exploratory analysis of multiple, diverse clinical datasets in the National Sleep Research Resource (NSRR). QARM enables rule mining on a subset of data items satisfying a query constraint. We first perform a series of data-preprocessing steps including variable selection, merging semantically similar variables, combining multiple-visit data, and data transformation. We use Top-k Non-Redundant (TNR) ARM algorithm to generate association rules. Then we remove general and subsumed rules so that unique and non-redundant rules are resulted for a particular query constraint. Results: Applying QARM on five datasets from NSRR obtained a total of 2517 association rules with a minimum confidence of 60% (using top 100 rules for each query constraint). The results show that merging similar variables could avoid uninteresting rules. Also, removing general and subsumed rules resulted in a more concise and interesting set of rules. Conclusions: QARM shows the potential to support exploratory analysis of large biomedical datasets. It is also shown as a useful method to reduce the number of uninteresting association rules generated from imbalanced datasets. A preliminary literature-based analysis showed that some association rules have supporting evidence from biomedical literature, while others without literature-based evidence may serve as the candidates for new hypotheses to explore and investigate. Together with literature-based evidence, the association rules mined over the NSRR clinical datasets may be used to support clinical decisions for sleep-related problems

FEDRR: Fast, Exhaustive Detection of Redundant Hierarchical Relations for Quality Improvement of Large Biomedical Ontologies

Background: Redundant hierarchical relations refer to such patterns as two paths from one concept to another, one with length one (direct) and the other with length greater than one (indirect). Each redundant relation represents a possibly unintended defect that needs to be corrected in the ontology quality assurance process. Detecting and eliminating redundant relations would help improve the results of all methods relying on the relevant ontological systems as knowledge source, such as the computation of semantic distance between concepts and for ontology matching and alignment. Results: This paper introduces a novel and scalable approach, called FEDRR – Fast, Exhaustive Detection of Redundant Relations – for quality assurance work during ontological evolution. FEDRR combines the algorithm ideas of Dynamic Programming with Topological Sort, for exhaustive mining of all redundant hierarchical relations in ontological hierarchies, in O(c·|V|+|E|) time, where |V| is the number of concepts, |E| is the number of the relations, and c is a constant in practice. Using FEDRR, we performed exhaustive search of all redundant is-a relations in two of the largest ontological systems in biomedicine: SNOMED CT and Gene Ontology (GO). 372 and 1609 redundant is-a relations were found in the 2015-09-01 version of SNOMED CT and 2015-05-01 version of GO, respectively. We have also performed FEDRR on over 190 source vocabularies in the UMLS - a large integrated repository of biomedical ontologies, and identified six sources containing redundant is-a relations. Randomly generated ontologies have also been used to further validate the efficiency of FEDRR. Conclusions: FEDRR provides a generally applicable, effective tool for systematic detecting redundant relations in large ontological systems for quality improvement

Auditing SNOMED CT Hierarchical Relations Based on Lexical Features of Concepts in Non-Lattice Subgraphs

Objective—We introduce a structural-lexical approach for auditing SNOMED CT using a combination of non-lattice subgraphs of the underlying hierarchical relations and enriched lexical attributes of fully specified concept names. Our goal is to develop a scalable and effective approach that automatically identifies missing hierarchical IS-A relations. Methods—Our approach involves 3 stages. In stage 1, all non-lattice subgraphs of SNOMED CT’s IS-A hierarchical relations are extracted. In stage 2, lexical attributes of fully-specified concept names in such non-lattice subgraphs are extracted. For each concept in a non-lattice subgraph, we enrich its set of attributes with attributes from its ancestor concepts within the non-lattice subgraph. In stage 3, subset inclusion relations between the lexical attribute sets of each pair of concepts in each non-lattice subgraph are compared to existing IS-A relations in SNOMED CT. For concept pairs within each non-lattice subgraph, if a subset relation is identified but an IS-A relation is not present in SNOMED CT IS-A transitive closure, then a missing IS-A relation is reported. The September 2017 release of SNOMED CT (US edition) was used in this investigation. Results—A total of 14,380 non-lattice subgraphs were extracted, from which we suggested a total of 41,357 missing IS-A relations. For evaluation purposes, 200 non-lattice subgraphs were randomly selected from 996 smaller subgraphs (of size 4, 5, or 6) within the “Clinical Finding” and “Procedure” sub-hierarchies. Two domain experts confirmed 185 (among 223) missing IS-A relations, a precision of 82.96%. Conclusions—Our results demonstrate that analyzing the lexical features of concepts in non-lattice subgraphs is an effective approach for auditing SNOMED CT

HyCLASSS: A Hybrid Classifier for Automatic Sleep Stage Scoring

Automatic identification of sleep stage is an important step in a sleep study. In this paper, we propose a hybrid automatic sleep stage scoring approach, named HyCLASSS, based on single channel electroencephalogram (EEG). HyCLASSS, for the first time, leverages both signal and stage transition features of human sleep for automatic identification of sleep stages. HyCLASSS consists of two parts: A random forest classifier and correction rules. Random forest classifier is trained using 30 EEG signal features, including temporal, frequency, and nonlinear features. The correction rules are constructed based on stage transition feature, importing the continuity property of sleep, and characteristic of sleep stage transition. Compared with the gold standard of manual scoring using Rechtschaffen and Kales criterion, the overall accuracy and kappa coefficient applied on 198 subjects has reached 85.95% and 0.8046 in our experiment, respectively. The performance of HyCLASS compared favorably to previous work, and it could be integrated with sleep evaluation or sleep diagnosis system in the future

Mining Non-Lattice Subgraphs for Detecting Missing Hierarchical Relations and Concepts in SNOMED CT

Objective: Quality assurance of large ontological systems such as SNOMED CT is an indispensable part of the terminology management lifecycle. We introduce a hybrid structural-lexical method for scalable and systematic discovery of missing hierarchical relations and concepts in SNOMED CT. Material and Methods: All non-lattice subgraphs (the structural part) in SNOMED CT are exhaustively extracted using a scalable MapReduce algorithm. Four lexical patterns (the lexical part) are identified among the extracted non-lattice subgraphs. Non-lattice subgraphs exhibiting such lexical patterns are often indicative of missing hierarchical relations or concepts. Each lexical pattern is associated with a potential specific type of error. Results: Applying the structural-lexical method to SNOMED CT (September 2015 US edition), we found 6801 non-lattice subgraphs that matched these lexical patterns, of which 2046 were amenable to visual inspection. We evaluated a random sample of 100 small subgraphs, of which 59 were reviewed in detail by domain experts. All the subgraphs reviewed contained errors confirmed by the experts. The most frequent type of error was missing is-a relations due to incomplete or inconsistent modeling of the concepts. Conclusions: Our hybrid structural-lexical method is innovative and proved effective not only in detecting errors in SNOMED CT, but also in suggesting remediation for these errors

Conversational ontology operator: Patient-centric vaccine dialogue management engine for spoken conversational agents

BACKGROUND: Previously, we introduced our Patient Health Information Dialogue Ontology (PHIDO) that manages the dialogue and contextual information of the session between an agent and a health consumer. In this study, we take the next step and introduce the Conversational Ontology Operator (COO), the software engine harnessing PHIDO. We also developed a question-answering subsystem called Frankenstein Ontology Question-Answering for User-centric Systems (FOQUS) to support the dialogue interaction. METHODS: We tested both the dialogue engine and the question-answering system using application-based competency questions and questions furnished from our previous Wizard of OZ simulation trials. RESULTS: Our results revealed that the dialogue engine is able to perform the core tasks of communicating health information and conversational flow. Inter-rater agreement and accuracy scores among four reviewers indicated perceived, acceptable responses to the questions asked by participants from the simulation studies, yet the composition of the responses was deemed mediocre by our evaluators. CONCLUSIONS: Overall, we present some preliminary evidence of a functioning ontology-based system to manage dialogue and consumer questions. Future plans for this work will involve deploying this system in a speech-enabled agent to assess its usage with potential health consumer users

NHash: Randomized N-Gram Hashing for Distributed Generation of Validatable Unique Study Identifiers in Multicenter Research

BACKGROUND: A unique study identifier serves as a key for linking research data about a study subject without revealing protected health information in the identifier. While sufficient for single-site and limited-scale studies, the use of common unique study identifiers has several drawbacks for large multicenter studies, where thousands of research participants may be recruited from multiple sites. An important property of study identifiers is error tolerance (or validatable), in that inadvertent editing mistakes during their transmission and use will most likely result in invalid study identifiers. OBJECTIVE: This paper introduces a novel method called Randomized N-gram Hashing (NHash), for generating unique study identifiers in a distributed and validatable fashion, in multicenter research. NHash has a unique set of properties: (1) it is a pseudonym serving the purpose of linking research data about a study participant for research purposes; (2) it can be generated automatically in a completely distributed fashion with virtually no risk for identifier collision; (3) it incorporates a set of cryptographic hash functions based on N-grams, with a combination of additional encryption techniques such as a shift cipher; (d) it is validatable (error tolerant) in the sense that inadvertent edit errors will mostly result in invalid identifiers. METHODS: NHash consists of 2 phases. First, an intermediate string using randomized N-gram hashing is generated. This string consists of a collection of N-gram hashes f1, f2, ..., fk. The input for each function fi has 3 components: a random number r, an integer n, and input data m. The result, fi(r, n, m), is an n-gram of m with a starting position s, which is computed as (r mod |m|), where |m| represents the length of m. The output for Step 1 is the concatenation of the sequence f1(r1, n1, m1), f2(r2, n2, m2), ..., fk(rk, nk, mk). In the second phase, the intermediate string generated in Phase 1 is encrypted using techniques such as shift cipher. The result of the encryption, concatenated with the random number r, is the final NHash study identifier. RESULTS: We performed experiments using a large synthesized dataset comparing NHash with random strings, and demonstrated neglegible probability for collision. We implemented NHash for the Center for SUDEP Research (CSR), a National Institute for Neurological Disorders and Stroke-funded Center Without Walls for Collaborative Research in the Epilepsies. This multicenter collaboration involves 14 institutions across the United States and Europe, bringing together extensive and diverse expertise to understand sudden unexpected death in epilepsy patients (SUDEP). CONCLUSIONS: The CSR Data Repository has successfully used NHash to link deidentified multimodal clinical data collected in participating CSR institutions, meeting all desired objectives of NHash

X-search: An Open Access Interface for Cross-Cohort Exploration of the National Sleep Research Resource

Background: The National Sleep Research Resource (NSRR) is a large-scale, openly shared, data repository of de-identified, highly curated clinical sleep data from multiple NIH-funded epidemiological studies. Although many data repositories allow users to browse their content, few support fine-grained, cross-cohort query and exploration at study-subject level. We introduce a cross-cohort query and exploration system, called X-search, to enable researchers to query patient cohort counts across a growing number of completed, NIH-funded studies in NSRR and explore the feasibility or likelihood of reusing the data for research studies. Methods: X-search has been designed as a general framework with two loosely-coupled components: semantically annotated data repository and cross-cohort exploration engine. The semantically annotated data repository is comprised of a canonical data dictionary, data sources with a data dictionary, and mappings between each individual data dictionary and the canonical data dictionary. The cross-cohort exploration engine consists of five modules: query builder, graphical exploration, case-control exploration, query translation, and query execution. The canonical data dictionary serves as the unified metadata to drive the visual exploration interfaces and facilitate query translation through the mappings. Results: X-search is publicly available at https://www.x-search.net/ with nine NSRR datasets consisting of over 26,000 unique subjects. The canonical data dictionary contains over 900 common data elements across the datasets. X-search has received over 1800 cross-cohort queries by users from 16 countries. Conclusions: X-search provides a powerful cross-cohort exploration interface for querying and exploring heterogeneous datasets in the NSRR data repository, so as to enable researchers to evaluate the feasibility of potential research studies and generate potential hypotheses using the NSRR data

Web-Based Interactive Mapping from Data Dictionaries to Ontologies, with an Application to Cancer Registry

BACKGROUND: The Kentucky Cancer Registry (KCR) is a central cancer registry for the state of Kentucky that receives data about incident cancer cases from all healthcare facilities in the state within 6 months of diagnosis. Similar to all other U.S. and Canadian cancer registries, KCR uses a data dictionary provided by the North American Association of Central Cancer Registries (NAACCR) for standardized data entry. The NAACCR data dictionary is not an ontological system. Mapping between the NAACCR data dictionary and the National Cancer Institute (NCI) Thesaurus (NCIt) will facilitate the enrichment, dissemination and utilization of cancer registry data. We introduce a web-based system, called Interactive Mapping Interface (IMI), for creating mappings from data dictionaries to ontologies, in particular from NAACCR to NCIt. METHOD: IMI has been designed as a general approach with three components: (1) ontology library; (2) mapping interface; and (3) recommendation engine. The ontology library provides a list of ontologies as targets for building mappings. The mapping interface consists of six modules: project management, mapping dashboard, access control, logs and comments, hierarchical visualization, and result review and export. The built-in recommendation engine automatically identifies a list of candidate concepts to facilitate the mapping process. RESULTS: We report the architecture design and interface features of IMI. To validate our approach, we implemented an IMI prototype and pilot-tested features using the IMI interface to map a sample set of NAACCR data elements to NCIt concepts. 47 out of 301 NAACCR data elements have been mapped to NCIt concepts. Five branches of hierarchical tree have been identified from these mapped concepts for visual inspection. CONCLUSIONS: IMI provides an interactive, web-based interface for building mappings from data dictionaries to ontologies. Although our pilot-testing scope is limited, our results demonstrate feasibility using IMI for semantic enrichment of cancer registry data by mapping NAACCR data elements to NCIt concepts