Featured Publications
SANTO: a coarse-to-fine alignment and stitching method for spatial omics
Li H, Lin Y, He W, Han W, Xu X, Xu C, Gao E, Zhao H, Gao X. SANTO: a coarse-to-fine alignment and stitching method for spatial omics. Nature Communications 2024, 15: 6048. PMID: 39025895, PMCID: PMC11258319, DOI: 10.1038/s41467-024-50308-x.Peer-Reviewed Original ResearchTuning parameters for polygenic risk score methods using GWAS summary statistics from training data
Jiang W, Chen L, Girgenti M, Zhao H. Tuning parameters for polygenic risk score methods using GWAS summary statistics from training data. Nature Communications 2024, 15: 24. PMID: 38169469, PMCID: PMC10762162, DOI: 10.1038/s41467-023-44009-0.Peer-Reviewed Original ResearchscNAT: a deep learning method for integrating paired single-cell RNA and T cell receptor sequencing profiles
Zhu B, Wang Y, Ku L, van Dijk D, Zhang L, Hafler D, Zhao H. scNAT: a deep learning method for integrating paired single-cell RNA and T cell receptor sequencing profiles. Genome Biology 2023, 24: 292. PMID: 38111007, PMCID: PMC10726524, DOI: 10.1186/s13059-023-03129-y.Peer-Reviewed Original ResearchA statistical framework to identify cell types whose genetically regulated proportions are associated with complex diseases
Liu W, Deng W, Chen M, Dong Z, Zhu B, Yu Z, Tang D, Sauler M, Lin C, Wain L, Cho M, Kaminski N, Zhao H. A statistical framework to identify cell types whose genetically regulated proportions are associated with complex diseases. PLOS Genetics 2023, 19: e1010825. PMID: 37523391, PMCID: PMC10414598, DOI: 10.1371/journal.pgen.1010825.Peer-Reviewed Original ResearchConceptsCell typesDisease-associated tissuesWide association studyComplex diseasesCell type proportionsDisease-relevant tissuesReal GWAS dataFunctional genesTranscriptomic dataGWAS dataGenetic dataAssociation studiesNovel statistical frameworkChronic obstructive pulmonary diseaseStatistical frameworkObstructive pulmonary diseaseIdiopathic pulmonary fibrosisBreast cancer riskType proportionsBlood CD8Pulmonary diseasePulmonary fibrosisPredictive biomarkersLung tissueBreast cancerSDPRX: A statistical method for cross-population prediction of complex traits
Zhou G, Chen T, Zhao H. SDPRX: A statistical method for cross-population prediction of complex traits. American Journal Of Human Genetics 2022, 110: 13-22. PMID: 36460009, PMCID: PMC9892700, DOI: 10.1016/j.ajhg.2022.11.007.Peer-Reviewed Original ResearchConceptsStatistical methodsJoint distributionWide association study (GWAS) summary statisticsNon-European populationsReal traitsSummary statisticsCross-population predictionPrediction accuracyGenome-wide association study summary statisticsLinkage disequilibrium differencesPrediction performancePolygenic risk scoresComplex traitsStatisticsSimulationsApplicationsTraitsNetwork assisted analysis of de novo variants using protein-protein interaction information identified 46 candidate genes for congenital heart disease
Xie Y, Jiang W, Dong W, Li H, Jin SC, Brueckner M, Zhao H. Network assisted analysis of de novo variants using protein-protein interaction information identified 46 candidate genes for congenital heart disease. PLOS Genetics 2022, 18: e1010252. PMID: 35671298, PMCID: PMC9205499, DOI: 10.1371/journal.pgen.1010252.Peer-Reviewed Original ResearchLeveraging LD eigenvalue regression to improve the estimation of SNP heritability and confounding inflation
Song S, Jiang W, Zhang Y, Hou L, Zhao H. Leveraging LD eigenvalue regression to improve the estimation of SNP heritability and confounding inflation. American Journal Of Human Genetics 2022, 109: 802-811. PMID: 35421325, PMCID: PMC9118121, DOI: 10.1016/j.ajhg.2022.03.013.Peer-Reviewed Original ResearchConceptsLinkage disequilibrium score regressionComplex traitsSingle nucleotide polymorphismsSNP heritabilityGenome-wide association studiesDisequilibrium score regressionHigh-throughput technologiesHeritable phenotypesAssociation studiesGenetic studiesCryptic relatednessLD informationScore regressionHeritabilityGenetic contributionHeritability estimationPopulation stratificationDisease mechanismsTraitsLD matrixOnly summary statisticsUK BiobankPolygenicitySummary statisticsRelatednessM-DATA: A statistical approach to jointly analyzing de novo mutations for multiple traits
Xie Y, Li M, Dong W, Jiang W, Zhao H. M-DATA: A statistical approach to jointly analyzing de novo mutations for multiple traits. PLOS Genetics 2021, 17: e1009849. PMID: 34735430, PMCID: PMC8568192, DOI: 10.1371/journal.pgen.1009849.Peer-Reviewed Original ResearchSUPERGNOVA: local genetic correlation analysis reveals heterogeneous etiologic sharing of complex traits
Zhang Y, Lu Q, Ye Y, Huang K, Liu W, Wu Y, Zhong X, Li B, Yu Z, Travers BG, Werling DM, Li JJ, Zhao H. SUPERGNOVA: local genetic correlation analysis reveals heterogeneous etiologic sharing of complex traits. Genome Biology 2021, 22: 262. PMID: 34493297, PMCID: PMC8422619, DOI: 10.1186/s13059-021-02478-w.Peer-Reviewed Original ResearchConceptsLocal genetic correlationsComplex traitsGenetic correlationsGenomic regionsLocal genetic correlation analysisGenome-wide association studiesLocal genomic regionsSpecific genomic regionsGenetic correlation analysisDistinct genetic signaturesGenetic similarityGenetic signaturesAssociation studiesTraitsSample overlapStatistical frameworkSummary statisticsDisequilibriumRegionAccurate estimationSimilarityA fast and robust Bayesian nonparametric method for prediction of complex traits using summary statistics
Zhou G, Zhao H. A fast and robust Bayesian nonparametric method for prediction of complex traits using summary statistics. PLOS Genetics 2021, 17: e1009697. PMID: 34310601, PMCID: PMC8341714, DOI: 10.1371/journal.pgen.1009697.Peer-Reviewed Original ResearchConceptsBayesian nonparametric methodParameter tuningNonparametric methodsExternal reference panelSummary statisticsComputational resourcesParallel algorithmBlock structureExplicit assumptionsExisting methodsStatisticsSeparate validation dataAccurate risk prediction modelsAssumptionPrediction modelPredictionAlgorithmTranscriptomic organization of the human brain in post-traumatic stress disorder
Girgenti MJ, Wang J, Ji D, Cruz DA, Stein M, Gelernter J, Young K, Huber B, Williamson D, Friedman M, Krystal J, Zhao H, Duman R. Transcriptomic organization of the human brain in post-traumatic stress disorder. Nature Neuroscience 2020, 24: 24-33. PMID: 33349712, DOI: 10.1038/s41593-020-00748-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAutopsyBrain ChemistryCohort StudiesDepressive Disorder, MajorFemaleGene Expression RegulationGene Regulatory NetworksGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInterneuronsMaleMiddle AgedNerve Tissue ProteinsSex CharacteristicsStress Disorders, Post-TraumaticTranscriptomeYoung AdultConceptsGenome-wide association studiesSignificant gene networksDifferential gene expressionSystems-level evidenceSignificant genetic liabilityMajor depressive disorder cohortGene networksTranscriptomic organizationTranscriptomic landscapeDownregulated setsGenomic networksGene expressionAssociation studiesMolecular determinantsExtensive remodelingGenotype dataSexual dimorphismSignificant divergenceMolecular profileNetwork analysisELFN1TranscriptsDimorphismPostmortem tissueDivergence
2024
Single-cell transcriptomic and proteomic analysis of Parkinson’s disease brains
Zhu B, Park J, Coffey S, Russo A, Hsu I, Wang J, Su C, Chang R, Lam T, Gopal P, Ginsberg S, Zhao H, Hafler D, Chandra S, Zhang L. Single-cell transcriptomic and proteomic analysis of Parkinson’s disease brains. Science Translational Medicine 2024, 16: eabo1997. PMID: 39475571, DOI: 10.1126/scitranslmed.abo1997.Peer-Reviewed Original ResearchConceptsProteomic analysisAlzheimer's diseasePrefrontal cortexBrain cell typesGenetics of PDParkinson's diseaseCell-cell interactionsChaperone expressionSingle-nucleus transcriptomesExpressed genesTranscriptional changesPostmortem human brainPostmortem brain tissueDiseased brainSynaptic proteinsSingle-cellDown-regulationBrain cell populationsBrain regionsCell typesNeurodegenerative disordersLate-stage PDParkinson's disease brainsDisease etiologyNeuronal vulnerabilityLDER-GE estimates phenotypic variance component of gene–environment interactions in human complex traits accurately with GE interaction summary statistics and full LD information
Dong Z, Jiang W, Li H, DeWan A, Zhao H. LDER-GE estimates phenotypic variance component of gene–environment interactions in human complex traits accurately with GE interaction summary statistics and full LD information. Briefings In Bioinformatics 2024, 25: bbae335. PMID: 38980374, PMCID: PMC11232466, DOI: 10.1093/bib/bbae335.Peer-Reviewed Original ResearchConceptsHuman complex traitsComplex traitsGene-environment interactionsGene-environmentLinkage disequilibriumPhenotypic variance componentsPhenotypic varianceProportion of phenotypic varianceSummary statisticsEuropean ancestry subjectsUK Biobank dataAssociation summary statisticsComplete linkage disequilibriumControlled type I error ratesLD informationLD matrixVariance componentsBiobank dataType I error rateEuropean ancestrySample size increaseGenetic effectsTraitsE-I pairsSimulation studyStatistical methods for assessing the effects of de novo variants on birth defects
Xie Y, Wu R, Li H, Dong W, Zhou G, Zhao H. Statistical methods for assessing the effects of de novo variants on birth defects. Human Genomics 2024, 18: 25. PMID: 38486307, PMCID: PMC10938830, DOI: 10.1186/s40246-024-00590-z.Peer-Reviewed Original ResearchConceptsDe novo variantsAnalyzed de novo variantsDevelopment of next-generation sequencing technologiesNext-generation sequencing technologiesSequencing technologiesImprove statistical powerGenetic heterogeneitySequenced samplesStatistical powerBirth defectsDiseased individualsLow occurrenceCongenital heart diseaseVariantsGenesDeleterious effectsSequenceGeneral workflowStatistical methodsPhenome- and genome-wide analyses of retinal optical coherence tomography images identify links between ocular and systemic health
Zekavat S, Jorshery S, Rauscher F, Horn K, Sekimitsu S, Koyama S, Nguyen T, Costanzo M, Jang D, Burtt N, Kühnapfel A, Shweikh Y, Ye Y, Raghu V, Zhao H, Ghassemi M, Elze T, Segrè A, Wiggs J, Del Priore L, Scholz M, Wang J, Natarajan P, Zebardast N. Phenome- and genome-wide analyses of retinal optical coherence tomography images identify links between ocular and systemic health. Science Translational Medicine 2024, 16: eadg4517. PMID: 38266105, DOI: 10.1126/scitranslmed.adg4517.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesRetinal layer thicknessPhotoreceptor segmentsOptical coherence tomographyRetinal layersUK Biobank participantsLIFE-Adult-StudyInherited genetic lociGenome-wide associationGanglion cell complex layerRetinal optical coherence tomography imagesRetinal nerve fiber layerAge-related macular degenerationBiobank participantsEye careNerve fiber layerOptical coherence tomography imagesIncident mortalityMacular OCT imagesLIFE-AdultIndependent associationsAssociation studiesSystemic healthGenetic associationGenome-wide analysis
2023
Profilin1 is required to prevent mitotic catastrophe in murine and human glomerular diseases
Tian X, Pedigo C, Li K, Ma X, Bunda P, Pell J, Lek A, Gu J, Zhang Y, Rangel P, Li W, Schwartze E, Nagata S, Lerner G, Perincheri S, Priyadarshini A, Zhao H, Lek M, Menon M, Fu R, Ishibe S. Profilin1 is required to prevent mitotic catastrophe in murine and human glomerular diseases. Journal Of Clinical Investigation 2023, 133: e171237. PMID: 37847555, PMCID: PMC10721156, DOI: 10.1172/jci171237.Peer-Reviewed Original ResearchConceptsProteinuric kidney diseaseKidney diseasePodocyte lossHuman glomerular diseasesMitotic catastrophePodocyte cell cycleSevere proteinuriaCell cycle reentryKidney failureGlomerular diseaseCell cycleKidney tissueG1/S checkpointUnsuccessful repairCyclin D1Glomerular integrityIrregular nucleiTissue-specific lossMouse podocytesPodocytesAltered expressionDiseaseCyclin B1Ribosome affinity purificationMultinucleated cellsCell-type-specific co-expression inference from single cell RNA-sequencing data
Su C, Xu Z, Shan X, Cai B, Zhao H, Zhang J. Cell-type-specific co-expression inference from single cell RNA-sequencing data. Nature Communications 2023, 14: 4846. PMID: 37563115, PMCID: PMC10415381, DOI: 10.1038/s41467-023-40503-7.Peer-Reviewed Original ResearchMulti-trait genome-wide association analyses leveraging alcohol use disorder findings identify novel loci for smoking behaviors in the Million Veteran Program
Cheng Y, Dao C, Zhou H, Li B, Kember R, Toikumo S, Zhao H, Gelernter J, Kranzler H, Justice A, Xu K. Multi-trait genome-wide association analyses leveraging alcohol use disorder findings identify novel loci for smoking behaviors in the Million Veteran Program. Translational Psychiatry 2023, 13: 148. PMID: 37147289, PMCID: PMC10162964, DOI: 10.1038/s41398-023-02409-2.Peer-Reviewed Original ResearchConceptsSingle-trait genome-wide association studiesGenome-wide association studiesNovel lociPower of GWASJoint genome-wide association studyGenome-wide significant lociMillion Veteran ProgramGenome-wide associationSubstance use traitsGWAS summary statisticsNovel genetic variantsMulti-trait analysisFunctional annotationUse traitsSignificant lociHeritable traitMultiple lociAssociation studiesColocalization analysisLociPleiotropic effectsMTAgVeteran ProgramGenetic variantsTraitsEarly breast cancer risk detection: a novel framework leveraging polygenic risk scores and machine learning
Tao L, Ye Y, Zhao H. Early breast cancer risk detection: a novel framework leveraging polygenic risk scores and machine learning. Journal Of Medical Genetics 2023, 60: 960-964. PMID: 37055164, DOI: 10.1136/jmg-2022-108582.Peer-Reviewed Original ResearchConceptsBreast cancerPolygenic risk scoresRisk scoreBC risk assessmentClinical breast examNon-genetic risk factorsHigh-risk individualsFemale participantsBreast examCancer deathCommon cancerBC screeningRisk factorsBC diagnosisDisease risk predictionDiagnostic stepsPopulation screeningGenetic riskRisk predictionUK BiobankCancerDiagnosisDiagnostic pipelineWomenDetection testEstimation on risk of spontaneous abortions by genomic disorders from a meta‐analysis of microarray results on large case series of pregnancy losses
Peng G, Zhou Q, Chai H, Wen J, Zhao H, Taylor H, Jiang Y, Li P. Estimation on risk of spontaneous abortions by genomic disorders from a meta‐analysis of microarray results on large case series of pregnancy losses. Molecular Genetics & Genomic Medicine 2023, 11: e2181. PMID: 37013615, PMCID: PMC10422064, DOI: 10.1002/mgg3.2181.Peer-Reviewed Original ResearchConceptsGenomic disordersChromosome microarray analysisWilliams-Beuren syndromePathogenic copy number variantsPopulation genetic studiesWolf-Hirschhorn syndromeCopy number variantsDiGeorge syndromeMicroarray analysisMicroarray resultsChromosomal abnormalitiesGenetic studiesNumber variantsGenetic counseling