JBASE: Joint Bayesian Analysis of Subphenotypes and Epistasis

Motivation: Rapid advances in genotyping and genome-wide association studies have enabled the discovery of many new genotype–phenotype associations at the resolution of individual markers. However, these associations explain only a small proportion of theoretically estimated heritability of most diseases. In this work, we propose an integrative mixture model called JBASE: joint Bayesian analysis of subphenotypes and epistasis. JBASE explores two major reasons of missing heritability: interactions between genetic variants, a phenomenon known as epistasis and phenotypic heterogeneity, addressed via subphenotyping. Results: Our extensive simulations in a wide range of scenarios repeatedly demonstrate that JBASE can identify true underlying subphenotypes, including their associated variants and their interactions, with high precision. In the presence of phenotypic heterogeneity, JBASE has higher Power and lower Type 1 Error than five state-of-the-art approaches. We applied our method to a sample of individuals from Mexico with Type 2 diabetes and discovered two novel epistatic modules, including two loci each, that define two subphenotypes characterized by differences in body mass index and waist-to-hip ratio. We successfully replicated these subphenotypes and epistatic modules in an independent dataset from Mexico genotyped with a different platform. Availability and implementation: JBASE is implemented in Cþþ, supported on Linux and is available at http://www.cs.toronto.edu/goldenberg/JBASE/jbase.tar.gz. The genotype data underlying this study are available upon approval by the ethics review board of the Medical Centre Siglo XXI.No sponso

Sensitization to Aeroallergens in Korean Children: A Population-based Study in 2010

We performed this study to assess the prevalence of sensitization to aeroallergens and to analyze the difference between prevalence rates according to children's ages and residential areas. In this nationwide cross-sectional study, first grade students of 45 elementary schools and 40 middle schools were randomly selected, and skin prick tests were performed for 18 inhalant allergens between October and November 2010. Of 7,829 analyzed subjects, 3,753 (47.9%) were sensitized to at least one aeroallergen. Sensitization to Dermatophagoides farinae was found to be the most prevalent in elementary schoolchildren (32.4%), followed by Dermatophagoides pteronyssinus, Tyrophagus putrescentiae, Japanese hop, and oak. In middle schoolchildren, D. pteronyssinus yielded the highest prevalence (42.7%), followed by D. farinae, T. putrescentiae, Japanese hop, and cat. In middle schoolchildren, the sensitization rate to aeroallergens in metropolitan, urban, and rural areas was 57.2%, 54.3%, and 49.8%, respectively (P = 0.019). In this age group, the sensitization rate in low, middle, high, and very high income groups was 53.8%, 51.8%, 59.0%, and 59.6%, respectively (P = 0.002). In conclusion, the sensitization rate is 47.9% and house dust mite is the most prevalent allergen in the pediatric population in Korea. The rate is higher in metropolitan areas and the highest income group than in rural areas and low income groups

Integrative and Comparative Genomic Analysis of Lung Squamous Cell Carcinomas in East Asian Patients

Lung squamous cell carcinoma (SCC) is the second most prevalent type of lung cancer. Currently, no targeted therapeutics are approved for treatment of this cancer, largely because of a lack of systematic understanding of the molecular pathogenesis of the disease. To identify therapeutic targets and perform comparative analyses of lung SCC, we probed somatic genome alterations of lung SCC by using samples from Korean patients

Identification and Validation of the Regulators of Riboneogenesis

The riboneogenesis pathway provides yeast with an alternate route for ribose production. Ribose is an essential precursor for nucleotide synthesis. Riboneogenesis connects glycolysis to the non-oxidative pentose phosphate pathway by the action of the key enzyme, Shb17, which converts sedoheptulose-1,7,-bisphosphate into sedoheptulose-7-phosphate. To understand why this pathway evolved and to gain insight into ribose metabolism in yeast, I used fluorescence based assays to identify genetic regulators of Shb17. Using reporter fluorescence, I probed the levels of Shb17 across the budding yeast prototrophic deletion collection using both a Typhoon fluorescent imager as well as flow cytometry. My screens identified genes involved in ribosome biogenesis as potential regulators of Shb17, which were validated by immunoblotting and further characterized by polysome profiling. My results raise the hypothesis that the relative level of the 60S to the 40S ribosomal subunit influence the regulation of Shb17.M.Sc.2019-11-08 00:00:0

The Application of Knowledge-Based Clinical Decision Support Systems to Detect Antibiotic Allergy

Prevention of drug allergies is important for patient safety. The objective of this study was to evaluate the outcomes of antibiotic allergy-checking clinical decision support system (CDSS), K-CDSTM. A retrospective chart review study was performed in 29 hospitals and antibiotic allergy alerts data were collected from May to August 2022. A total of 15,535 allergy alert cases from 1586 patients were reviewed. The most frequently prescribed antibiotics were cephalosporins (48.5%), and there were more alerts of potential cross-reactivity between beta-lactam antibiotics than between antibiotics with the same ingredients or of the same class. Regarding allergy symptoms, dermatological disorders were the most common (38.8%), followed by gastrointestinal disorders (28.4%). The 714 cases (4.5%) of immune system disorders included 222 cases of anaphylaxis and 61 cases of severe cutaneous adverse reactions. Alerts for severe symptoms were reported in 6.4% of all cases. This study confirmed that K-CDS can effectively detect antibiotic allergies and prevent the prescription of potentially allergy-causing antibiotics among patients with a history of antibiotic allergies. If K-CDS is expanded to medical institutions nationwide in the future, it can prevent an increase in allergy recurrence related to drug prescriptions through cloud-based allergy detection CDSSs

Shared Interoperable Clinical Decision Support Service for Drug-Allergy Interaction Checks: Implementation Study

BackgroundClinical decision support (CDS) can improve health care with respect to the quality of care, patient safety, efficiency, and effectiveness. Establishing a CDS system in a health care setting remains a challenge. A few hospitals have used self-developed in-house CDS systems or commercial CDS solutions. Since these in-house CDS systems tend to be tightly coupled with a specific electronic health record system, the functionality and knowledge base are not easily shareable. A shared interoperable CDS system facilitates the sharing of the knowledge base and extension of CDS services. ObjectiveThe study focuses on developing and deploying the national CDS service for the drug-allergy interaction (DAI) check for health care providers in Korea that need to introduce the service but lack the budget and expertise. MethodsTo provide the shared interoperable CDS service, we designed and implemented the system based on the CDS Hooks specification and Health Level Seven (HL7) Fast Healthcare Interoperability Resources (FHIR) standard. The study describes the CDS development process. The system development went through requirement analysis, design, implementation, and deployment. In particular, the concept architecture was designed based on the CDS Hooks structure. The MedicationRequest and AllergyIntolerance resources were profiled to exchange data using the FHIR standard. The discovery and DAI check application programming interfaces and rule engine were developed. ResultsThe CDS service was deployed on G-Cloud, a government cloud service. In March 2021, the CDS service was launched, and 67 health care providers participated in the CDS service. The health care providers participated in the service with 1,008,357 DAI checks for 114,694 patients, of which 33,054 (3.32%) cases resulted in a “warning.” ConclusionsKorea’s Ministry of Health and Welfare has been trying to build an HL7 FHIR-based ecosystem in Korea. As one of these efforts, the CDS service initiative has been conducted. To promote the rapid adoption of the HL7 FHIR standard, it is necessary to accelerate practical service development and to appeal to policy makers regarding the benefits of FHIR standardization. With the development of various case-specific implementation guides using the Korea Core implementation guide, the FHIR standards will be distributed nationwide, and more shared interoperable health care services will be introduced in Korea