2025
Trio exome sequencing identifies de novo variants in novel candidate genes in 19.62% of CAKUT families
Merz L, Kolvenbach C, Wang C, Mertens N, Seltzsam S, Mansour B, Zheng B, Schneider S, Schierbaum L, Hölzel S, Salmanullah D, Pantel D, Kalkar G, Connaughton D, Mann N, Wu C, Kause F, Nakayama M, Dai R, Schneider R, Buerger F, Nicolas-Frank C, Yousef K, Lemberg K, Saida K, Yu S, Elmubarak I, Franken G, Lomjansook K, Braun A, Bauer S, Rodig N, Somers M, Traum A, Stein D, Daga A, Baum M, Daouk G, Awad H, Eid L, El Desoky S, Shalaby M, Kari J, Ooda S, Fathy H, Soliman N, Nabhan M, Abdelrahman S, Hilger A, Mane S, Ferguson M, Tasic V, Shril S, Hildebrandt F. Trio exome sequencing identifies de novo variants in novel candidate genes in 19.62% of CAKUT families. Genetics In Medicine 2025, 27: 101432. PMID: 40223730, DOI: 10.1016/j.gim.2025.101432.Peer-Reviewed Original ResearchCandidate genesExome sequencingDisease genesPotential novel candidate genesCandidate disease genesTrio-based exome sequencingDe novo variantsTrio exome sequencingDisease etiologyPathogenesis of CAKUTPotential novel causeTrio familiesTrio analysisMonogenic genesGenesNovel causeCHD1LSOX13VariantsTriosSequenceCongenital anomaliesHeterogeneous malformationUrinary tractCAKUTDiversifying Psychiatric Genomics Globally Inclusive Strategies Toward Health Equity
Giusti-Rodríguez P, Okewole N, Jain S, Montalvo-Ortiz J, Peterson R. Diversifying Psychiatric Genomics Globally Inclusive Strategies Toward Health Equity. Psychiatric Clinics Of North America 2025, 48: 241-256. PMID: 40348415, DOI: 10.1016/j.psc.2025.01.003.Peer-Reviewed Original ResearchConceptsPerpetuate health inequitiesHealth care outcomesMental health conditionsHealth inequalitiesCare outcomesMental healthHealth conditionsAncestral diversityPsychiatric geneticsCapacity buildingData useDisease etiologyEnvironmental factorsPrecision medicineClinical impactGlobal collaborationHealthParticipantsResearch methodOutcomesMedicineGeneticsPopulationPracticeResearch
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 vulnerabilityElectome network factors: Capturing emotional brain networks related to health and disease
Walder-Christensen K, Abdelaal K, Klein H, Thomas G, Gallagher N, Talbot A, Adamson E, Rawls A, Hughes D, Mague S, Dzirasa K, Carlson D. Electome network factors: Capturing emotional brain networks related to health and disease. Cell Reports Methods 2024, 4: 100691. PMID: 38215761, PMCID: PMC10832286, DOI: 10.1016/j.crmeth.2023.100691.Peer-Reviewed Original ResearchConceptsCognitive processesEmotional brain networksBrain networksMental disordersFunctional connectomeTranslational biomarkersBrain statesBehavioral contextDisordersHeterogeneous disorderRelevant networksPrevalence of illnessBiologically relevant networksMoodCircuit insightAffectConvergence mechanismConnectomeBrainIllnessNext-generation therapeuticsDisease etiologyTherapeutic developmentIndividuals
2023
From function to translation: Decoding genetic susceptibility to human diseases via artificial intelligence
Long E, Wan P, Chen Q, Lu Z, Choi J. From function to translation: Decoding genetic susceptibility to human diseases via artificial intelligence. Cell Genomics 2023, 3: 100320. PMID: 37388909, PMCID: PMC10300605, DOI: 10.1016/j.xgen.2023.100320.Peer-Reviewed Original ResearchDisease-associated lociWide association studyNovel biological insightsFunctional genomicsPost-GWASGWAS findingsGWA findingsBiological insightsMolecular mechanismsAssociation studiesHuman diseasesGenetic associationFunctional datasetsLociDisease etiologyGenetic susceptibilityGenomicsConsiderable fractionFive Critical Gene-Based Biomarkers With Optimal Performance for Hepatocellular Carcinoma
Liu Y, Zhang H, Xu Y, Liu Y, Al-Adra D, Yeh M, Zhang Z. Five Critical Gene-Based Biomarkers With Optimal Performance for Hepatocellular Carcinoma. Cancer Informatics 2023, 22: 11769351231190477. PMID: 37577174, PMCID: PMC10413891, DOI: 10.1177/11769351231190477.Peer-Reviewed Original ResearchModel gene-gene interactionsCorrecting batch effectsGene-gene interactionsPublished transcriptomic studiesAnalysis of human cancersGene-based biomarkersWhole-transcriptome datasetsGenomic levelTranscriptome dataTranscriptomic studiesBatch effectsEffective therapeutic targetDEGsHuman cancersDisease etiologyMolecular backgroundCaucasian cohortTherapeutic targetIdentified 5Signature patternsIdentification of biomarkersConceptual advancesMiniaturized setting
2022
Dynamic quality control machinery that operates across compartmental borders mediates the degradation of mammalian nuclear membrane proteins
Tsai P, Cameron C, Forni M, Wasko R, Naughton B, Horsley V, Gerstein M, Schlieker C. Dynamic quality control machinery that operates across compartmental borders mediates the degradation of mammalian nuclear membrane proteins. Cell Reports 2022, 41: 111675. PMID: 36417855, PMCID: PMC9827541, DOI: 10.1016/j.celrep.2022.111675.Peer-Reviewed Original ResearchConceptsProtein turnoverCellular quality control systemNuclear membrane proteinsQuality control machineryDistinct cellular compartmentsNuclear envelope proteinsGenetic screenProtein homeostasisUbiquitin ligasesControl machineryMembrane proteinsCellular compartmentsEnzyme Ube2g2Quality control systemEndoplasmic reticulumHuman diseasesEfficient biosynthesisHRD1RNF5Disease variantsTMEM33Envelope proteinSubstrate levelsDisease etiologyModel substrateLINE-1 activation in the cerebellum drives ataxia
Takahashi T, Stoiljkovic M, Song E, Gao XB, Yasumoto Y, Kudo E, Carvalho F, Kong Y, Park A, Shanabrough M, Szigeti-Buck K, Liu ZW, Kristant A, Zhang Y, Sulkowski P, Glazer PM, Kaczmarek LK, Horvath TL, Iwasaki A. LINE-1 activation in the cerebellum drives ataxia. Neuron 2022, 110: 3278-3287.e8. PMID: 36070749, PMCID: PMC9588660, DOI: 10.1016/j.neuron.2022.08.011.Peer-Reviewed Original ResearchConceptsLINE-1 activationL1 activationAtaxia telangiectasia patientsNuclear element-1Transposable elementsEpigenetic silencersHuman genomeL1 promoterMolecular regulatorsDNA damagePurkinje cell dysfunctionElement 1First direct evidenceTelangiectasia patientsDirect targetingCerebellar expressionNeurodegenerative diseasesDisease etiologyCalcium homeostasisImproving detection of cerebral small vessel disease aetiology in patients with isolated lobar intracerebral haemorrhage
Das A, Gokcal E, Regenhardt R, Horn M, Schwab K, Daoud N, Viswanathan A, Kimberly W, Goldstein J, Biffi A, Rost N, Rosand J, Schwamm L, Greenberg S, Gurol M. Improving detection of cerebral small vessel disease aetiology in patients with isolated lobar intracerebral haemorrhage. Stroke And Vascular Neurology 2022, 8: 26-33. PMID: 35981809, PMCID: PMC9985798, DOI: 10.1136/svn-2022-001653.Peer-Reviewed Original ResearchConceptsLeft ventricular hypertrophyCerebral amyloid angiopathyLobar intracerebral hemorrhageIntracerebral hemorrhageImaging markerFrequency of LVHCerebral small vessel diseaseSmall vessel diseaseAetiologic groupsLobar lacunesAmyloid angiopathyVentricular hypertrophyVessel diseasePresence/distributionPatientsDisease etiologyHemorrhageLacunesMarkersRegression modelsAngiopathyHigh frequencyHypertrophyEtiologyDisease
2021
Premetastatic shifts of endogenous and exogenous mutational processes support consolidative therapy in EGFR-driven lung adenocarcinoma
Fisk JN, Mahal AR, Dornburg A, Gaffney SG, Aneja S, Contessa JN, Rimm D, Yu JB, Townsend JP. Premetastatic shifts of endogenous and exogenous mutational processes support consolidative therapy in EGFR-driven lung adenocarcinoma. Cancer Letters 2021, 526: 346-351. PMID: 34780851, PMCID: PMC8702484, DOI: 10.1016/j.canlet.2021.11.011.Peer-Reviewed Original ResearchConceptsMutational processesSingle ancestral lineageAncestral lineageProgression of cancerMetastatic lineagesPhylogenetic analysisGenetic resistanceEvolutionary processesExogenous mutational processesCancer evolutionConsolidative therapyMutational signature analysisEGFR-positive non-small cell lung cancerNon-small cell lung cancerKey eventsLineagesCell populationsTherapeutic resistanceLocal consolidative therapyClinical time courseCell lung cancerDisease etiologyTherapeutic decision makingCisplatin therapyLung cancer
2019
An unbiased approach de-livers unexpected insight into torsin biology
Prophet SM, Schlieker C. An unbiased approach de-livers unexpected insight into torsin biology. Journal Of Clinical Investigation 2019, 129: 4576-4579. PMID: 31589164, PMCID: PMC6819095, DOI: 10.1172/jci132442.Peer-Reviewed Original ResearchConceptsFatty liver diseaseHepatic lipid metabolismLiver diseaseNonneural tissuesLipid metabolismBrain functionConditional deletionCongenital disorderDisease etiologySecretion defectHuman pathologiesMammalian liverPolypeptide 1Future investigationsSteatohepatitisUnbiased approachDysfunctionVLDLEtiologyMutationsDiseaseMiceLiverNeuronsPathologySocial media partnerships with patient organizations for neuro-oncology patient recruitment
Claus EB, Feliciano J, Benz LS, Calvocoressi L. Social media partnerships with patient organizations for neuro-oncology patient recruitment. Neuro-Oncology Practice 2019, 7: 143-151. PMID: 32626583, PMCID: PMC7318861, DOI: 10.1093/nop/npz049.Peer-Reviewed Original ResearchNeuro-oncology patientsPatient organizationsNational Cancer Institute's SurveillanceEnd Results (SEER) dataTumor RegistryPathology reportsTreatment responsePatient recruitmentEpidemiologic studiesNeuro-oncologyPatientsYale University SchoolSaliva specimenSuccessful enrollmentEnrollment methodsDisease etiologyAssociation websitesRegistryPublic healthUniversity SchoolParticipant populationResult dataSurveillanceOnline questionnaireParticipantsAblation of SUN2-containing LINC complexes drives cardiac hypertrophy without interstitial fibrosis
Stewart RM, Rodriguez EC, King MC. Ablation of SUN2-containing LINC complexes drives cardiac hypertrophy without interstitial fibrosis. Molecular Biology Of The Cell 2019, 30: 1664-1675. PMID: 31091167, PMCID: PMC6727752, DOI: 10.1091/mbc.e18-07-0438.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCardiomegalyCell AdhesionCell Nucleus ShapeDNA-Binding ProteinsFibrosisGene DeletionIntegrinsMAP Kinase Signaling SystemMembrane ProteinsMice, Inbred C57BLMice, KnockoutMultiprotein ComplexesMyocardiumNuclear EnvelopeProto-Oncogene Proteins c-aktSarcomeresTelomere-Binding ProteinsTransforming Growth Factor betaConceptsLINC complexType laminsInner nuclear membrane protein MAN1Nuclear envelopeA-type laminsSarcomeric contractile apparatusNuclear laminaDisease etiologyProfibrotic signalingCytoskeletal linkageAKT/MAPK signalingCardiomyocyte cytoskeletonPlasma membraneMAPK signalingNegative regulatorAntagonistic rolesTGFβ signalingLaminsCellular adhesionSignalingCardiac hypertrophySUN2Human cardiomyopathyHypertrophy markersContractile apparatusLipidomics for wildlife disease etiology and biomarker discovery: a case study of pansteatitis outbreak in South Africa
Koelmel J, Ulmer C, Fogelson S, Jones C, Botha H, Bangma J, Guillette T, Luus-Powell W, Sara J, Smit W, Albert K, Miller H, Guillette M, Olsen B, Cochran J, Garrett T, Yost R, Bowden J. Lipidomics for wildlife disease etiology and biomarker discovery: a case study of pansteatitis outbreak in South Africa. Metabolomics 2019, 15: 38. PMID: 30838461, PMCID: PMC11005104, DOI: 10.1007/s11306-019-1490-9.Peer-Reviewed Original ResearchConceptsApplication of lipidomicsDiverse biological rolesWildlife studiesPossible disease mechanismsClasses of lipidsHigh-resolution tandem mass spectrometryLoskop DamBiological roleMozambique tilapiaCell deathMortality eventsPansteatitisLipidomicsOxidative damageDisease mechanismsAdipose tissuePromising biomarker candidatesBiomarker discoveryDisease etiologyTilapiaTandem mass spectrometryCeramideAquatic lifeLipidomeBiomarker candidates
2018
The Open Translational Science in Schizophrenia (OPTICS) project: an open-science project bringing together Janssen clinical trial and NIMH data
Wilcox MA, Savitz AJ, Addington AM, Gray GS, Guinan EC, Jackson JW, Lehner T, Normand SL, Ranu H, Senthil G, Spertus J, Valeri L, Ross JS. The Open Translational Science in Schizophrenia (OPTICS) project: an open-science project bringing together Janssen clinical trial and NIMH data. Schizophrenia 2018, 4: 14. PMID: 29950580, PMCID: PMC6021398, DOI: 10.1038/s41537-018-0055-7.Commentaries, Editorials and LettersClinical trialsOverall public health burdenSchizophrenia ProjectPublic health burdenClinical trial dataReal-world studyTranslational scienceHarvard CatalystHealth burdenTherapeutic safetyTrial dataBrain diseasesBiology of diseaseGold standardBest treatmentPharmaceutical safetyDisease etiologyTrialsDiseaseEfficacyProject investigatorsSafetyEtiologySchizophreniaA Role for the Non-Receptor Tyrosine Kinase Abl2/Arg in Experimental Neuroinflammation
Jacobsen FA, Scherer AN, Mouritsen J, Bragadóttir H, Thomas Bäckström B, Sardar S, Holmberg D, Koleske AJ, Andersson Å. A Role for the Non-Receptor Tyrosine Kinase Abl2/Arg in Experimental Neuroinflammation. Journal Of Neuroimmune Pharmacology 2018, 13: 265-276. PMID: 29550892, PMCID: PMC5928183, DOI: 10.1007/s11481-018-9783-8.Peer-Reviewed Original ResearchConceptsMultiple sclerosisExperimental autoimmune encephalomyelitis (EAE) modelT cell receptorCongenic mouse strainsExperimental neuroinflammationInflammation pathogenesisMyelin antigensEAE developmentExperimental arthritisAutoimmune responseImmune cellsDisease susceptibility factorsCongenic miceLymphocyte activationPharmacological inhibitionAbl kinaseSclerosisSusceptibility factorsMouse strainsDegenerative diseasesPotential drug targetsMouse genetic locusSingle nucleotide polymorphismsDisease etiologyAmino acid changesEffect of outside referrals to a tertiary care liver tumor board on diagnostic testing and initial curative therapy.
Zhang Y, Arango J, Weinreb J, Taddei T. Effect of outside referrals to a tertiary care liver tumor board on diagnostic testing and initial curative therapy. Journal Of Clinical Oncology 2018, 36: 259-259. DOI: 10.1200/jco.2018.36.4_suppl.259.Peer-Reviewed Original ResearchMultidisciplinary tumor boardInitial curative therapyTertiary care centerLiver disease etiologyCurative therapyBCLC stageHepatocellular carcinomaCare centerTumor boardOutside institutionCases of HCCIncident HCC casesUniversity-affiliated hospitalDisease etiologyDiagnostic imaging protocolOptimal treatment planDiagnostic methodsChart reviewInitial treatmentTertiary careHCC casesOutside referralsOutside facilityTumor biopsiesAmerican College
2017
LipidMatch: an automated workflow for rule-based lipid identification using untargeted high-resolution tandem mass spectrometry data
Koelmel J, Kroeger N, Ulmer C, Bowden J, Patterson R, Cochran J, Beecher C, Garrett T, Yost R. LipidMatch: an automated workflow for rule-based lipid identification using untargeted high-resolution tandem mass spectrometry data. BMC Bioinformatics 2017, 18: 331. PMID: 28693421, PMCID: PMC5504796, DOI: 10.1186/s12859-017-1744-3.Peer-Reviewed Original ResearchConceptsLipid identificationNumerous biological functionsHigh-resolution tandem mass spectrometry dataMass spectrometry workflowsUncharacterized adductsBiological functionsLipid typeStructural detailsLipid-based biomarkersPathway perturbationsTandem mass spectrometry dataSpectral similarity scoreCorrect annotationLipid speciesMass spectrometry dataLiquid chromatography-tandem mass spectrometry (LC-MS/MS) workflowSilico FragmentMass spectrometry experimentsLipid candidatesEtiology of diseaseLipid moleculesAnnotationFatty acyl constituentsBiomarker discoveryDisease etiology
2016
Recalibrating the Child–Turcotte–Pugh Score to Improve Prediction of Transplant-Free Survival in Patients with Cirrhosis
Kaplan DE, Dai F, Skanderson M, Aytaman A, Baytarian M, D’Addeo K, Fox R, Hunt K, Knott A, Mehta R, Pedrosa M, Pocha C, Valderrama A, Taddei T, for the VOCAL Study Group. Recalibrating the Child–Turcotte–Pugh Score to Improve Prediction of Transplant-Free Survival in Patients with Cirrhosis. Digestive Diseases And Sciences 2016, 61: 3309-3320. PMID: 27405990, PMCID: PMC5067291, DOI: 10.1007/s10620-016-4239-6.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBilirubinCreatinineDisease ProgressionEnd Stage Liver DiseaseEvidence-Based MedicineFemaleHumansInternational Normalized RatioLiver CirrhosisLiver TransplantationMaleMiddle AgedOdds RatioPrognosisProportional Hazards ModelsRetrospective StudiesSerum AlbuminSeverity of Illness IndexUnited StatesVeteransConceptsTransplant-free survivalHarrell's C-statisticC-statisticPugh scoreChild-TurcotteCTP scoreHighest Harrell's C-statisticsCox proportional hazards modelEvidence-based cutpointProportional hazards modelLong-term survivalEtiology subgroupsSerum creatinineVeteran patientsLaboratory variablesRisk ratioTotal bilirubinHazards modelCirrhosisPatientsLower cutpointsDisease etiologySurvivalCutpointsScoresTranscriptional Profiles from Paired Normal Samples Offer Complementary Information on Cancer Patient Survival – Evidence from TCGA Pan-Cancer Data
Huang X, Stern DF, Zhao H. Transcriptional Profiles from Paired Normal Samples Offer Complementary Information on Cancer Patient Survival – Evidence from TCGA Pan-Cancer Data. Scientific Reports 2016, 6: 20567. PMID: 26837275, PMCID: PMC4738355, DOI: 10.1038/srep20567.Peer-Reviewed Original ResearchConceptsPatient survivalTumor cell contaminationField cancerization effectNormal samplesCancer patient survivalNormal tissue samplesSitu immunizationCancer Genome AtlasCancer patientsPatient progressionNormal controlsTumorsNormal tissuesPan-cancer dataTissue samplesGenome AtlasCancer studiesDisease etiologyCell contaminationPatientsPathway analysisTCGA pan-cancer dataSurvivalTranscriptional profilesPotential benefits
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