2024
Single-cell genomics and regulatory networks for 388 human brains
Emani P, Liu J, Clarke D, Jensen M, Warrell J, Gupta C, Meng R, Lee C, Xu S, Dursun C, Lou S, Chen Y, Chu Z, Galeev T, Hwang A, Li Y, Ni P, Zhou X, Bakken T, Bendl J, Bicks L, Chatterjee T, Cheng L, Cheng Y, Dai Y, Duan Z, Flaherty M, Fullard J, Gancz M, Garrido-Martín D, Gaynor-Gillett S, Grundman J, Hawken N, Henry E, Hoffman G, Huang A, Jiang Y, Jin T, Jorstad N, Kawaguchi R, Khullar S, Liu J, Liu J, Liu S, Ma S, Margolis M, Mazariegos S, Moore J, Moran J, Nguyen E, Phalke N, Pjanic M, Pratt H, Quintero D, Rajagopalan A, Riesenmy T, Shedd N, Shi M, Spector M, Terwilliger R, Travaglini K, Wamsley B, Wang G, Xia Y, Xiao S, Yang A, Zheng S, Gandal M, Lee D, Lein E, Roussos P, Sestan N, Weng Z, White K, Won H, Girgenti M, Zhang J, Wang D, Geschwind D, Gerstein M, Akbarian S, Abyzov A, Ahituv N, Arasappan D, Almagro Armenteros J, Beliveau B, Berretta S, Bharadwaj R, Bhattacharya A, Brennand K, Capauto D, Champagne F, Chatzinakos C, Chen H, Cheng L, Chess A, Chien J, Clement A, Collado-Torres L, Cooper G, Crawford G, Dai R, Daskalakis N, Davila-Velderrain J, Deep-Soboslay A, Deng C, DiPietro C, Dracheva S, Drusinsky S, Duong D, Eagles N, Edelstein J, Galani K, Girdhar K, Goes F, Greenleaf W, Guo H, Guo Q, Hadas Y, Hallmayer J, Han X, Haroutunian V, He C, Hicks S, Ho M, Ho L, Huang Y, Huuki-Myers L, Hyde T, Iatrou A, Inoue F, Jajoo A, Jiang L, Jin P, Jops C, Jourdon A, Kellis M, Kleinman J, Kleopoulos S, Kozlenkov A, Kriegstein A, Kundaje A, Kundu S, Li J, Li M, Lin X, Liu S, Liu C, Loupe J, Lu D, Ma L, Mariani J, Martinowich K, Maynard K, Myers R, Micallef C, Mikhailova T, Ming G, Mohammadi S, Monte E, Montgomery K, Mukamel E, Nairn A, Nemeroff C, Norton S, Nowakowski T, Omberg L, Page S, Park S, Patowary A, Pattni R, Pertea G, Peters M, Pinto D, Pochareddy S, Pollard K, Pollen A, Przytycki P, Purmann C, Qin Z, Qu P, Raj T, Reach S, Reimonn T, Ressler K, Ross D, Rozowsky J, Ruth M, Ruzicka W, Sanders S, Schneider J, Scuderi S, Sebra R, Seyfried N, Shao Z, Shieh A, Shin J, Skarica M, Snijders C, Song H, State M, Stein J, Steyert M, Subburaju S, Sudhof T, Snyder M, Tao R, Therrien K, Tsai L, Urban A, Vaccarino F, van Bakel H, Vo D, Voloudakis G, Wang T, Wang S, Wang Y, Wei Y, Weimer A, Weinberger D, Wen C, Whalen S, Willsey A, Wong W, Wu H, Wu F, Wuchty S, Wylie D, Yap C, Zeng B, Zhang P, Zhang C, Zhang B, Zhang Y, Ziffra R, Zeier Z, Zintel T. Single-cell genomics and regulatory networks for 388 human brains. Science 2024, 384: eadi5199. PMID: 38781369, PMCID: PMC11365579, DOI: 10.1126/science.adi5199.Peer-Reviewed Original ResearchConceptsSingle-cell genomicsSingle-cell expression quantitative trait locusExpression quantitative trait lociDrug targetsQuantitative trait lociPopulation-level variationSingle-cell expressionCell typesDisease-risk genesTrait lociGene familyRegulatory networksGene expressionCell-typeMultiomics datasetsSingle-nucleiGenomeGenesCellular changesHeterogeneous tissuesExpressionCellsChromatinLociMultiomicsTuning 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 Research
2022
Genetic liability to suicidal thoughts and behaviors and risk of suicide attempt in US military veterans: moderating effects of cumulative trauma burden
Nichter B, Koller D, De Angelis F, Wang J, Girgenti M, Na P, Hill M, Norman S, Krystal J, Gelernter J, Polimanti R, Pietrzak R. Genetic liability to suicidal thoughts and behaviors and risk of suicide attempt in US military veterans: moderating effects of cumulative trauma burden. Psychological Medicine 2022, 53: 6325-6333. PMID: 36444557, DOI: 10.1017/s0033291722003646.Peer-Reviewed Original ResearchConceptsPolygenic risk scoresUS military veteransLifetime suicide attemptsSuicide attemptsTrauma exposureTrauma burdenGenetic liabilityMilitary veteransDrug repurposing analysisPopulation-based sampleCumulative trauma exposureLifetime trauma exposureLow trauma exposureSuicide prediction modelsChronic inflammationInflammatory processNervous system developmentRisk scorePsychiatric characteristicsSuicidal behaviorExposure interactionsLarge genome-wide association studiesHigh levelsVeteransSuicidalityVenus: An efficient virus infection detection and fusion site discovery method using single-cell and bulk RNA-seq data
Lee CY, Chen Y, Duan Z, Xu M, Girgenti MJ, Xu K, Gerstein M, Zhang J. Venus: An efficient virus infection detection and fusion site discovery method using single-cell and bulk RNA-seq data. PLOS Computational Biology 2022, 18: e1010636. PMID: 36301997, PMCID: PMC9642901, DOI: 10.1371/journal.pcbi.1010636.Peer-Reviewed Original ResearchConceptsHBV-hepatocellular carcinomaAntiretroviral therapyHIV infectionImmune cellsT cellsViral pathophysiologyNeurological patientsNovel targetVirusInfection detectionVirus of interestPotential pathogensVirus detectionBulk RNA-seq dataCell typesViral transcriptsSingle-cell sequencingRNA-seq dataPublic healthcareCellsHIVPatientsCarcinomaPathogensPathophysiologyMolecular and cellular evolution of the primate dorsolateral prefrontal cortex
Ma S, Skarica M, Li Q, Xu C, Risgaard RD, Tebbenkamp ATN, Mato-Blanco X, Kovner R, Krsnik Ž, de Martin X, Luria V, Martí-Pérez X, Liang D, Karger A, Schmidt DK, Gomez-Sanchez Z, Qi C, Gobeske KT, Pochareddy S, Debnath A, Hottman CJ, Spurrier J, Teo L, Boghdadi AG, Homman-Ludiye J, Ely JJ, Daadi EW, Mi D, Daadi M, Marín O, Hof PR, Rasin MR, Bourne J, Sherwood CC, Santpere G, Girgenti MJ, Strittmatter SM, Sousa AMM, Sestan N. Molecular and cellular evolution of the primate dorsolateral prefrontal cortex. Science 2022, 377: eabo7257. PMID: 36007006, PMCID: PMC9614553, DOI: 10.1126/science.abo7257.Peer-Reviewed Original ResearchConceptsMolecular differencesSingle-nucleus transcriptomesSubset of speciesNeuropsychiatric risk genesCellular evolutionCellular repertoireEvolutionary specializationDorsolateral prefrontal cortexRate-limiting enzymeDivergent featuresRisk genesAnthropoid primatesPrefrontal cortexPrimate dorsolateral prefrontal cortexCertain interneuronsNeuropeptide somatostatinDopamine productionGranular neuronsTyrosine hydroxylaseCell subtypesExpressionTranscriptomeAdult humansGenesPrimatesMatthew J. Friedman, M.D., Ph.D. and His Legacy of Leadership in the Field of Post-traumatic Stress Disorder
Krystal JH, Southwick SM, Girgenti MJ. Matthew J. Friedman, M.D., Ph.D. and His Legacy of Leadership in the Field of Post-traumatic Stress Disorder. Psychiatry 2022, 85: 161-170. PMID: 35588483, DOI: 10.1080/00332747.2022.2068931.Peer-Reviewed Original Research
2021
Posttraumatic Stress Disorder Brain Transcriptomics: Convergent Genomic Signatures Across Biological Sex
Wang J, Zhao H, Girgenti MJ. Posttraumatic Stress Disorder Brain Transcriptomics: Convergent Genomic Signatures Across Biological Sex. Biological Psychiatry 2021, 91: 6-13. PMID: 33840456, DOI: 10.1016/j.biopsych.2021.02.012.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsPosttraumatic stress disorderConvergent genomic signaturesSpecific cell typesGene regulationGenomic regulationGenomic signaturesGenomic technologiesMolecular determinantsCell typesBrains of malesMolecular effectsGABAergic signalingMolecular pathologyImmune functionPTSD brainsSex impactRegulationStress disorderStructural differencesEffects of sex
2020
Transcriptomic 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 tissueDivergenceStress and Its Impact on the Transcriptome
Girgenti MJ, Pothula S, Newton SS. Stress and Its Impact on the Transcriptome. Biological Psychiatry 2020, 90: 102-108. PMID: 33637305, PMCID: PMC8213869, DOI: 10.1016/j.biopsych.2020.12.011.Peer-Reviewed Original ResearchConceptsTranscriptomic dysregulationMajor gene expression changesGene expression changesDevelopmental time pointsAnimal modelsGenomic studiesNeuropsychiatric disordersTranscriptomic methodsAnimal kingdomComparable animal modelsGene expressionExpression changesEarly life stressPhenotypic signaturesSex-specific changesTransgenerational impactTranscriptomeSingle cellsEntire brain regionsPowerful approachDiseased brainBrain regionsChronic stressMolecular profileSame disorderCortical Transcriptomic Alterations in Association With Appetitive Neuropeptides and Body Mass Index in Posttraumatic Stress Disorder
Stone LA, Girgenti MJ, Wang J, Ji D, Zhao H, Krystal JH, Duman R. Cortical Transcriptomic Alterations in Association With Appetitive Neuropeptides and Body Mass Index in Posttraumatic Stress Disorder. The International Journal Of Neuropsychopharmacology 2020, 24: 118-129. PMID: 32951025, PMCID: PMC8611677, DOI: 10.1093/ijnp/pyaa072.Peer-Reviewed Original ResearchConceptsUpstream regulatorGene co-expression network analysisCo-expression network analysisFunctional genomic studiesPutative upstream regulatorsIngenuity Pathway Analysis softwarePathway Analysis softwarePathway annotationGenomic studiesTranscriptomic modulesTranscriptomic dataTranscriptomic alterationsGene expressionPTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies
Bhatt S, Hillmer AT, Girgenti MJ, Rusowicz A, Kapinos M, Nabulsi N, Huang Y, Matuskey D, Angarita GA, Esterlis I, Davis MT, Southwick SM, Friedman MJ, Duman R, Carson R, Krystal J, Pietrzak R, Cosgrove K. PTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies. Nature Communications 2020, 11: 2360. PMID: 32398677, PMCID: PMC7217830, DOI: 10.1038/s41467-020-15930-5.Peer-Reviewed Original ResearchMeSH KeywordsAcetamidesAdaptor Proteins, Signal TransducingAdultBrainCase-Control StudiesFemaleGene Expression ProfilingHealthy VolunteersHumansMaleMicrogliaMiddle AgedPositron-Emission TomographyPyridinesRadiopharmaceuticalsReceptors, GABAReceptors, Tumor Necrosis Factor, Member 14Sex FactorsStress Disorders, Post-TraumaticYoung AdultConceptsPosttraumatic stress disorderPeripheral immune activationImmune activationHigher C-reactive protein levelsC-reactive protein levelsTSPO availabilityTranslocator proteinBrain microglial activationTomography brain imagingStress-related pathophysiologyPositron emission tomography (PET) brain imagingNeuroimmune activationMicroglial activationPTSD symptom severityImmunologic regulationPostmortem studiesPTSD subgroupHealthy individualsSymptom severityTrauma exposurePTSD groupStress disorderLower relative expressionBrain imagingPET imaging
2018
Analysis of Bulk Tissue Transcriptome Data Reveals Convergence of Cell Types Altered in Schizophrenia and Bipolar Disorder
Girgenti MJ, Duman RS. Analysis of Bulk Tissue Transcriptome Data Reveals Convergence of Cell Types Altered in Schizophrenia and Bipolar Disorder. Biological Psychiatry 2018, 84: 772-774. PMID: 30409264, DOI: 10.1016/j.biopsych.2018.09.014.Peer-Reviewed Original ResearchMolecular and cellular studies of PTSD: Postmortem transcriptome analysis and novel therapeutic targets
Duman RS, Girgenti MJ. Molecular and cellular studies of PTSD: Postmortem transcriptome analysis and novel therapeutic targets. Journal Of Neuroscience Research 2018, 97: 292-299. PMID: 30136735, DOI: 10.1002/jnr.24306.Peer-Reviewed Original ResearchConceptsFear memoryPrefrontal cortexPTSD patientsFear memory processesNeurobiology of PTSDMemory processesInhibitory controlNeurobiological underpinningsPFC subregionsPTSD subjectsPTSDMemory studiesBrain regionsMemorySpecific gene expression alterationsNovel therapeutic targetPostmortem brain tissueEfficacious treatmentNeurobiologySynaptic alterationsSynapse numberEarlier findingsRodent modelsTherapeutic targetGene expression alterations
2017
Transcriptome Alterations in Posttraumatic Stress Disorder
Girgenti MJ, Duman RS. Transcriptome Alterations in Posttraumatic Stress Disorder. Biological Psychiatry 2017, 83: 840-848. PMID: 29128043, DOI: 10.1016/j.biopsych.2017.09.023.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderNext-generation sequencing technologiesAberrant gene expressionGene expression changesAmount of transcriptsGene expression studiesGene profiling studiesAlternative splicingTranscriptome alterationsTranscriptomic technologiesRNA sequencingSequencing technologiesTranscript identificationExpression studiesGene expressionExpression changesStress disorderBlood of patientsCellular mechanismsPeripheral blood cellsProfiling studiesHuman peripheral bloodPeripheral bloodLifetime prevalenceGeneral populationMolecular and Cellular Effects of Traumatic Stress: Implications for PTSD
Girgenti MJ, Hare BD, Ghosal S, Duman RS. Molecular and Cellular Effects of Traumatic Stress: Implications for PTSD. Current Psychiatry Reports 2017, 19: 85. PMID: 28944401, PMCID: PMC5907804, DOI: 10.1007/s11920-017-0841-3.Peer-Reviewed Original ResearchConceptsPathophysiology of PTSDPreclinical modelsReviewPosttraumatic stress disorderPeripheral blood studiesMolecular changesGlucocorticoid receptor signalingPrimary brain regionsPeripheral bloodInflammatory systemBlood studiesGlucocorticoid signalingHuman studiesPTSD patientsMolecular alterationsBrain regionsStress disorderAltered gene expressionPathophysiologyReceptor signalingCellular pathophysiologyNeurobiological determinantsCellular effectsMechanistic evidencePTSDPatientsAltered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence
Holmes SE, Girgenti MJ, Davis MT, Pietrzak RH, DellaGioia N, Nabulsi N, Matuskey D, Southwick S, Duman RS, Carson RE, Krystal JH, Esterlis I, Friedman M, Kowall N, Brady C, McKee A, Stein T, Huber B, Kaloupek D, Alvarez V, Benedek D, Ursano R, Williamson D, Cruz D, Young K, Duman R, Krystal J, Mash D, Hardegree M, Serlin G. Altered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 8390-8395. PMID: 28716937, PMCID: PMC5547601, DOI: 10.1073/pnas.1701749114.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderMGluR5 availabilityPositron emission tomographyGlutamate systemMetabotropic glutamate receptor 5Treatment of PTSDHuman posttraumatic stress disorderGlutamate receptor 5Mechanism-based treatmentsExpression of FKBP5Promising treatment targetHuman postmortem tissueTargeted pharmacological treatmentStress psychopathologyPharmacological treatmentExpression of proteinsReceptor 5MGluR5Treatment targetsPostmortem tissueEmission tomographyStress disorderPostmortem samplesPromising targetDisorders
2012
ZNF804a Regulates Expression of the Schizophrenia-Associated Genes PRSS16, COMT, PDE4B, and DRD2
Girgenti MJ, LoTurco JJ, Maher BJ. ZNF804a Regulates Expression of the Schizophrenia-Associated Genes PRSS16, COMT, PDE4B, and DRD2. PLOS ONE 2012, 7: e32404. PMID: 22384243, PMCID: PMC3288100, DOI: 10.1371/journal.pone.0032404.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesCatechol O-MethyltransferaseCell NucleusCyclic Nucleotide Phosphodiesterases, Type 4Gene Expression ProfilingGene Expression RegulationGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansImmunohistochemistryKruppel-Like Transcription FactorsRatsReceptors, Dopamine D2Recombinant ProteinsSchizophreniaSerine EndopeptidasesStem CellsTranscription, GeneticConceptsC2H2-type zinc finger domainsTranscript levelsPromoter regionGenome-wide statistical significanceZinc finger domainChromatin immunoprecipitation assaysWide association studyAmino acid sequenceRat neural progenitor cellsNeural progenitor cellsTranscriptional networksMolecular functionsTranscriptional controlSingle nucleotide polymorphismsImmunoprecipitation assaysDNA bindingAcid sequenceTranscription levelsAssociation studiesGenesNucleotide polymorphismsProgenitor cellsZNF804ATranscriptionDirect upregulation