2023
Endothelial Cell Response in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children
Kim J, Shimizu C, He M, Wang H, Hoffman H, Tremoulet A, Shyy J, Burns J. Endothelial Cell Response in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children. International Journal Of Molecular Sciences 2023, 24: 12318. PMID: 37569694, PMCID: PMC10418493, DOI: 10.3390/ijms241512318.Peer-Reviewed Original ResearchConceptsKawasaki diseaseEndothelial cellsCardiovascular outcomesInflammatory syndromeWeighted gene co-expression network analysisDifferent cardiovascular outcomesMultisystem inflammatory syndromePre-treatment serumEC homeostasisEndothelial-mesenchymal transitionCultured endothelial cellsPro-survival genesClinical manifestationsHealthy controlsImmune responseNFκB pathwayCell responsesEndothelial cell responsesDiseaseGene co-expression network analysisEC responseExpression levelsSyndromeCo-expression network analysisReduced transcriptsFamily and personal history of cancer in the All of Us research program for precision medicine
Bruce L, Paul P, Kim K, Kim J, Keegan T, Hiatt R, Ohno-Machado L, Investigators O. Family and personal history of cancer in the All of Us research program for precision medicine. PLOS ONE 2023, 18: e0288496. PMID: 37459328, PMCID: PMC10351738, DOI: 10.1371/journal.pone.0288496.Peer-Reviewed Original ResearchCommon and rare variants associated with cardiometabolic traits across 98,622 whole-genome sequences in the All of Us research program
Wang X, Ryu J, Kim J, Ramirez A, Mayo K, Condon H, Vaitinadin N, Ohno-Machado L, Talavera G, Ellinor P, Lubitz S, Choi S. Common and rare variants associated with cardiometabolic traits across 98,622 whole-genome sequences in the All of Us research program. Journal Of Human Genetics 2023, 68: 565-570. PMID: 37072623, PMCID: PMC10524735, DOI: 10.1038/s10038-023-01147-z.Peer-Reviewed Original ResearchConceptsDiverse human populationsGenomic dataGene-based burden testsWhole genome sequencesRare variant analysisHuman populationQuantitative traitsBurden testsRare lossLociComplex diseasesGenetic associationVariant analysisFunction variantsCardiometabolic traitsRare variantsTraitsBiomedical researchGIGYF1VariantsNPR2ACANSequencePopulationLDLRBlockchain-enabled immutable, distributed, and highly available clinical research activity logging system for federated COVID-19 data analysis from multiple institutions
Kuo T, Pham A, Edelson M, Kim J, Chan J, Gupta Y, Ohno-Machado L, Anderson D, Balacha C, Bath T, Baxter S, Becker-Pennrich A, Bell D, Bernstam E, Ngan C, Day M, Doctor J, DuVall S, El-Kareh R, Florian R, Follett R, Geisler B, Ghigi A, Gottlieb A, Hinske L, Hu Z, Ir D, Jiang X, Kim K, Kim J, Knight T, Koola J, Kuo T, Lee N, Mansmann U, Matheny M, Meeker D, Mou Z, Neumann L, Nguyen N, Nick A, Ohno-Machado L, Park E, Paul P, Pletcher M, Post K, Rieder C, Scherer C, Schilling L, Soares A, SooHoo S, Soysal E, Steven C, Tep B, Toy B, Wang B, Wu Z, Xu H, Yong C, Zheng K, Zhou Y, Zucker R. Blockchain-enabled immutable, distributed, and highly available clinical research activity logging system for federated COVID-19 data analysis from multiple institutions. Journal Of The American Medical Informatics Association 2023, 30: 1167-1178. PMID: 36916740, PMCID: PMC10198529, DOI: 10.1093/jamia/ocad049.Peer-Reviewed Original ResearchConceptsFederated data analysisUser activity logsSmart contract deploymentRun-time efficiencyData analysis systemData analysis activitiesActivity logsData discoveryQuerying timeBlockchain systemBlockchain technologyNetwork transactionsCOVID-19 data analysisMultiple institutionsLow deploymentBlockchainGitHub repositoryMultiple nodesLarge networksQueriesAnalysis activitiesHigh availabilityLanguage codeBaseline solutionData analysisWICOX: Weight-Based Integrated Cox Model for Time-to-Event Data in Distributed Databases Without Data-Sharing
Park J, Kim T, Kim J, Park Y. WICOX: Weight-Based Integrated Cox Model for Time-to-Event Data in Distributed Databases Without Data-Sharing. IEEE Journal Of Biomedical And Health Informatics 2023, 27: 526-537. PMID: 36318551, DOI: 10.1109/jbhi.2022.3218585.Peer-Reviewed Original ResearchConceptsLarge-scale biomedical dataPrivacy-preserving mannerPrivacy-protecting methodsCommon data modelPrivacy issuesDistributed DatabaseBiomedical dataData modelData networksIterative communicationCentralized modelPatient-level informationEvent dataSimulation resultsNon-iterative methodPredictive performanceRobust characteristicsRobust resultsMultiple institutionsDatabaseIntegrated modelAlgorithmNetworkCommunicationModel
2022
Comparative Safety and Effectiveness of Biologic Therapy for Crohn’s Disease: A CA-IBD Cohort Study
Singh S, Kim J, Luo J, Paul P, Rudrapatna V, Park S, Zheng K, Syal G, Ha C, Fleshner P, McGovern D, Sauk J, Limketkai B, Dulai P, Boland B, Eisenstein S, Ramamoorthy S, Melmed G, Mahadevan U, Sandborn W, Ohno-Machado L. Comparative Safety and Effectiveness of Biologic Therapy for Crohn’s Disease: A CA-IBD Cohort Study. Clinical Gastroenterology And Hepatology 2022, 21: 2359-2369.e5. PMID: 36343846, DOI: 10.1016/j.cgh.2022.10.029.Peer-Reviewed Original ResearchConceptsTNF-α antagonistsRisk of hospitalizationUstekinumab-treated patientsCrohn's diseaseSerious infectionsLower riskMulticenter cohortInflammatory bowel disease-related surgeryTumor necrosis factor α antagonistsNecrosis factor α antagonistsDisease-related surgeryHigher comorbidity burdenVedolizumab-treated patientsNew biologic agentsPropensity-score matchingComorbidity burdenCause hospitalizationAdult patientsBiologic therapyCohort studyPrior hospitalizationBiologic agentsΑ antagonistsBiologic classesComparative safetyRNA Sequencing Reveals Beneficial Effects of Atorvastatin on Endothelial Cells in Acute Kawasaki Disease
Shimizu C, Kim J, He M, Tremoulet A, Hoffman H, Shyy J, Burns J. RNA Sequencing Reveals Beneficial Effects of Atorvastatin on Endothelial Cells in Acute Kawasaki Disease. Journal Of The American Heart Association 2022, 11: e025408. PMID: 35861833, PMCID: PMC9707837, DOI: 10.1161/jaha.122.025408.Peer-Reviewed Original ResearchConceptsKawasaki diseaseGenome-wide transcriptional changesIntravenous immunoglobulinAcute Kawasaki diseaseHuman umbilical vein ECsInflammatory cell infiltrationEndothelial cell dysfunctionTumor necrosis factorTranscriptional changesRNA sequencingKD treatmentAcute phaseMyointimal proliferationCoronary arteryCell infiltrationCultured ECsNecrosis factorCell dysfunctionKD seraInterleukin-1Recruitment pathwayResponse of ECBackground damageSerumPatientsEffect of Obesity on Risk of Hospitalization, Surgery, and Serious Infection in Biologic-Treated Patients With Inflammatory Bowel Diseases: A CA-IBD Cohort Study
Gu P, Luo J, Kim J, Paul P, Limketkai B, Sauk J, Park S, Parekh N, Zheng K, Rudrapatna V, Syal G, Ha C, McGovern D, Melmed G, Fleshner P, Eisenstein S, Ramamoorthy S, Dulai P, Boland B, Grunvald E, Mahadevan U, Ohno-Machado L, Sandborn W, Singh S. Effect of Obesity on Risk of Hospitalization, Surgery, and Serious Infection in Biologic-Treated Patients With Inflammatory Bowel Diseases: A CA-IBD Cohort Study. The American Journal Of Gastroenterology 2022, 117: 1639-1647. PMID: 35973139, DOI: 10.14309/ajg.0000000000001855.Peer-Reviewed Original ResearchConceptsInflammatory bowel diseaseBiologic-treated patientsRisk of hospitalizationBody mass indexNormal body mass indexSerious infectionsBiologic agentsBowel diseaseCox proportional hazards analysisWorld Health Organization classificationEffect of obesityProportional hazards analysisElectronic health recordsCause hospitalizationVisceral obesityAdult patientsBaseline demographicsBiologic initiationBiologic therapyCohort studyEndoscopic outcomesMass indexOrganization classificationTreatment characteristicsStratified analysisEffectiveness and Safety of Biologic Therapy in Hispanic Vs Non-Hispanic Patients With Inflammatory Bowel Diseases: A CA-IBD Cohort Study
Nguyen N, Luo J, Paul P, Kim J, Syal G, Ha C, Rudrapatna V, Park S, Parekh N, Zheng K, Sauk J, Limketkai B, Fleshner P, Eisenstein S, Ramamoorthy S, Melmed G, Dulai P, Boland B, Mahadevan U, Sandborn W, Ohno-Machado L, McGovern D, Singh S. Effectiveness and Safety of Biologic Therapy in Hispanic Vs Non-Hispanic Patients With Inflammatory Bowel Diseases: A CA-IBD Cohort Study. Clinical Gastroenterology And Hepatology 2022, 21: 173-181.e5. PMID: 35644340, PMCID: PMC9701245, DOI: 10.1016/j.cgh.2022.05.008.Peer-Reviewed Original ResearchConceptsInflammatory bowel diseaseNon-Hispanic patientsBiologic-treated patientsHispanic patientsSerious infectionsBiologic therapyBowel diseasePropensity score-matched cohortBurden of inflammationRisk of hospitalizationHigh ratePropensity-score matchingCause hospitalizationAdult patientsBiologic initiationCohort studyBiologic agentsMedication useHigh burdenHigh riskHospitalizationPatientsSurvival analysisSurgeryAbstractTextAn Artificial Intelligence-guided signature reveals the shared host immune response in MIS-C and Kawasaki disease
Ghosh P, Katkar G, Shimizu C, Kim J, Khandelwal S, Tremoulet A, Kanegaye J, Bocchini J, Das S, Burns J, Sahoo D. An Artificial Intelligence-guided signature reveals the shared host immune response in MIS-C and Kawasaki disease. Nature Communications 2022, 13: 2687. PMID: 35577777, PMCID: PMC9110726, DOI: 10.1038/s41467-022-30357-w.Peer-Reviewed Original ResearchConceptsKawasaki diseaseHost immune responseLaboratory parametersImmune responseSARS-CoV-2 infectionInflammatory syndromeCytokine stormSerum cytokinesClinical featuresCytokine pathwaysCardiac phenotypeSyndromeGene signaturePediatric syndromesViral pandemicHeart tissueCOVID-19COVID-19 pandemicProximal pathwayDiseaseSeverityImmunopathogenesisPandemicCytokinesIllnessProtein and miRNA profile of circulating extracellular vesicles in patients with primary sclerosing cholangitis
Povero D, Tameda M, Eguchi A, Ren W, Kim J, Myers R, Goodman Z, Harrison S, Sanyal A, Bosch J, Ohno-Machado L, Feldstein A. Protein and miRNA profile of circulating extracellular vesicles in patients with primary sclerosing cholangitis. Scientific Reports 2022, 12: 3027. PMID: 35194091, PMCID: PMC8863778, DOI: 10.1038/s41598-022-06809-0.Peer-Reviewed Original ResearchConceptsSmall non-coding RNAsExtracellular vesiclesNon-coding RNAsNovel miRNAsControl subjectsFurther molecular characterizationMiRNA sequence analysisLiver-specific markersProtein profilingMiRNA cargoMolecular characterizationHuman diseasesCurrent serum markersNovel surrogate biomarkersPrimary sclerosing cholangitisCholestatic liver diseaseHealthy control subjectsMiRNA profilesProteinCell specificityDifferential centrifugationMiRNAsPSC patientsSclerosing cholangitisLiver disease
2021
No Benefit of Continuing 5-Aminosalicylates in Patients with Crohn’s Disease Treated with Anti-metabolite Therapy
Picetti D, Kim J, Zhu W, Sandborn W, Jairath V, Singh S. No Benefit of Continuing 5-Aminosalicylates in Patients with Crohn’s Disease Treated with Anti-metabolite Therapy. Digestive Diseases And Sciences 2021, 67: 3115-3123. PMID: 34797442, PMCID: PMC9117569, DOI: 10.1007/s10620-021-07301-x.Peer-Reviewed Original ResearchConceptsAnti-metabolite therapyCrohn's diseaseCox proportional hazards analysisCD-related hospitalizationCD-related surgeryAdministrative claims databaseProportional hazards analysisCorticosteroid useTreatment escalationClaims databaseClinical benefitResidual confoundingHigh riskPatientsDisease severityMonotherapyDiseaseKey covariatesTherapyHazard analysisOutcomesRiskEscalationMethodsPatientsHospitalizationBenchmarking blockchain-based gene-drug interaction data sharing methods: A case study from the iDASH 2019 secure genome analysis competition blockchain track
Kuo T, Bath T, Ma S, Pattengale N, Yang M, Cao Y, Hudson C, Kim J, Post K, Xiong L, Ohno-Machado L. Benchmarking blockchain-based gene-drug interaction data sharing methods: A case study from the iDASH 2019 secure genome analysis competition blockchain track. International Journal Of Medical Informatics 2021, 154: 104559. PMID: 34474309, PMCID: PMC9933142, DOI: 10.1016/j.ijmedinf.2021.104559.Peer-Reviewed Original ResearchConceptsSecure genome analysis competitionData retrieval queriesBlockchain-based methodData sharing methodReal-world problemsQuery indexType of sharingRetrieval queriesBlockchain technologyLedger technologySource codeBlockchain utilizationBlockchain strategyHealthcare applicationsInteraction recordsSharing methodTest datasetSharing recordsBiomedical research applicationsConsortium resourcesNew platformPatient recordsBlockchainQueriesTechnologyPrivacy-protecting, reliable response data discovery using COVID-19 patient observations
Kim J, Neumann L, Paul P, Day M, Aratow M, Bell D, Doctor J, Hinske L, Jiang X, Kim K, Matheny M, Meeker D, Pletcher M, Schilling L, SooHoo S, Xu H, Zheng K, Ohno-Machado L, Anderson D, Anderson N, Balacha C, Bath T, Baxter S, Becker-Pennrich A, Bernstam E, Carter W, Chau N, Choi Y, Covington S, DuVall S, El-Kareh R, Florian R, Follett R, Geisler B, Ghigi A, Gottlieb A, Hu Z, Ir D, Knight T, Koola J, Kuo T, Lee N, Mansmann U, Mou Z, Murphy R, Neumann L, Nguyen N, Niedermayer S, Park E, Perkins A, Post K, Rieder C, Scherer C, Soares A, Soysal E, Tep B, Toy B, Wang B, Wu Z, Zhou Y, Zucker R. Privacy-protecting, reliable response data discovery using COVID-19 patient observations. Journal Of The American Medical Informatics Association 2021, 28: 1765-1776. PMID: 34051088, PMCID: PMC8194878, DOI: 10.1093/jamia/ocab054.Peer-Reviewed Original ResearchKawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles
Jackson H, Menikou S, Hamilton S, McArdle A, Shimizu C, Galassini R, Huang H, Kim J, Tremoulet A, Thorne A, Fischer R, de Jonge M, Kuijpers T, Wright V, Burns J, Casals-Pascual C, Herberg J, Levin M, Kaforou M, On Behalf Of The Perform Consortium. Kawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles. International Journal Of Molecular Sciences 2021, 22: 5655. PMID: 34073389, PMCID: PMC8198135, DOI: 10.3390/ijms22115655.Peer-Reviewed Original ResearchConceptsKawasaki diseaseViral infectionHost responseKD patientsAcute inflammatory disordersAnti-bacterial responsePathway analysisBacterial patientsInflammatory disordersInflammatory responsePatient stratificationCommon triggerPatientsKD samplesHost transcriptomicsInfectionProteomic profilesOmics profilesDifferent triggersDiagnostic signatureResponseInflammationTriggersLevelsEtiologyVERTIcal Grid lOgistic regression with Confidence Intervals (VERTIGO-CI).
Kim J, Li W, Bath T, Jiang X, Ohno-Machado L. VERTIcal Grid lOgistic regression with Confidence Intervals (VERTIGO-CI). AMIA Joint Summits On Translational Science Proceedings 2021, 2021: 355-364. PMID: 34457150, PMCID: PMC8378611.Peer-Reviewed Original ResearchConceptsDual spaceCovariance matrixVariance estimationSpace modelTest statisticKernel matrixLinear modelReal dataTolerable performanceNovel extensionDual-space modelPoint estimatesEquivalent accuracyCentralized versionStatisticsRegression modelsModelMatrixExtensionDual objectivesCentralized settingFederated LearningEstimationPrivacy-preserving mannerSpaceIdentification of novel locus associated with coronary artery aneurysms and validation of loci for susceptibility to Kawasaki disease
Hoggart C, Shimizu C, Galassini R, Wright V, Shailes H, Bellos E, Herberg J, Pollard A, O’Connor D, Choi S, Seaby E, Menikou S, Hibberd M, Sallah N, Burgner D, Brogan P, Patel H, Kim J, Tremoulet A, Salo E, van Stijn D, Kuijpers T, Burns J, Levin M. Identification of novel locus associated with coronary artery aneurysms and validation of loci for susceptibility to Kawasaki disease. European Journal Of Human Genetics 2021, 29: 1734-1744. PMID: 33772158, PMCID: PMC7994355, DOI: 10.1038/s41431-021-00838-5.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesIntergenic regionNovel lociChromosome 20q13Second genome-wide association studyEuropean genome-wide association studyValidation of lociJapanese genome-wide association studiesGWAS summary dataAssociated lociGenomic regionsGenome dataPutative lociDifferent genesRisk allelesAssociation studiesEuropean descentLociGenetic variantsAllelesSNVsWider significanceGenesSusceptibilityCASP3Predictive Analytics for Glaucoma Using Data From the All of Us Research Program
Baxter S, Saseendrakumar B, Paul P, Kim J, Bonomi L, Kuo T, Loperena R, Ratsimbazafy F, Boerwinkle E, Cicek M, Clark C, Cohn E, Gebo K, Mayo K, Mockrin S, Schully S, Ramirez A, Ohno-Machado L, Investigators A. Predictive Analytics for Glaucoma Using Data From the All of Us Research Program. American Journal Of Ophthalmology 2021, 227: 74-86. PMID: 33497675, PMCID: PMC8184631, DOI: 10.1016/j.ajo.2021.01.008.Peer-Reviewed Original ResearchConceptsGlaucoma surgeryPrimary open-angle glaucomaOphthalmic researchSingle-center cohortElectronic health record dataMultivariable logistic regressionSingle-center dataOpen-angle glaucomaHealth record dataMean ageClaims dataUs Research ProgramLogistic regressionSurgeryRecord dataOphthalmic imagingCharacteristic curveExternal validationGlaucomaCohortAUCSingle-center model
2020
Genomics Links Inflammation With Neurocognitive Impairment in Children Living With Human Immunodeficiency Virus Type-1
Rawat P, Brummel S, Singh K, Kim J, Frazer K, Nichols S, Seage G, Williams P, Van Dyke R, Harismendy O, Trout R, Spector S. Genomics Links Inflammation With Neurocognitive Impairment in Children Living With Human Immunodeficiency Virus Type-1. The Journal Of Infectious Diseases 2020, 224: 870-880. PMID: 33373444, PMCID: PMC8408770, DOI: 10.1093/infdis/jiaa792.Peer-Reviewed Original ResearchMeSH Keywords14-3-3 ProteinsChildChild, PreschoolFemaleGenome-Wide Association StudyGenomicsHIV InfectionsHIV-1HumansInfantInfectious Disease Transmission, VerticalInflammasomesInflammationIntracellular Signaling Peptides and ProteinsMaleMembrane ProteinsMicrogliaNeurocognitive DisordersReceptors, CCRConceptsWhole-exome sequencingValidation cohortNeurocognitive impairmentOdds ratioRisk of NCIHuman immunodeficiency virus type 1Immunodeficiency virus type 1Single nucleotide variantsAdjusted odds ratioIL-1β releaseVirus type 1Microglial releaseIL-1βHuman microgliaDecreased oddsType 1Logistic regressionCognitive scoresCCRL2MicrogliaFurther studiesHIVInflammationCsACohortNo benefit of continuing vs stopping 5‐aminosalicylates in patients with ulcerative colitis escalated to anti‐metabolite therapy
Singh S, Kim J, Zhu W, Dulai P, Sandborn W, Jairath V. No benefit of continuing vs stopping 5‐aminosalicylates in patients with ulcerative colitis escalated to anti‐metabolite therapy. Alimentary Pharmacology & Therapeutics 2020, 52: 481-491. PMID: 32573825, PMCID: PMC8015755, DOI: 10.1111/apt.15876.Peer-Reviewed Original ResearchConceptsAnti-metabolite therapyUlcerative colitisCorticosteroid useRisk of UCCox proportional hazards analysisAdministrative claims databaseEmergency department visitsProportional hazards analysisComorbidity burdenTreatment escalationBiologic therapyAbdominal surgeryDepartment visitsClinical benefitClaims databaseResidual confoundingHigh riskPatientsDisease severityMonotherapyTherapyHospitalisationColitisSurgeryMonths