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-MartÃn 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 tissuesExpressionCellsChromatinLociMultiomics
2023
iHerd: an integrative hierarchical graph representation learning framework to quantify network changes and prioritize risk genes in disease
Duan Z, Dai Y, Hwang A, Lee C, Xie K, Xiao C, Xu M, Girgenti M, Zhang J. iHerd: an integrative hierarchical graph representation learning framework to quantify network changes and prioritize risk genes in disease. PLOS Computational Biology 2023, 19: e1011444. PMID: 37695793, PMCID: PMC10513318, DOI: 10.1371/journal.pcbi.1011444.Peer-Reviewed Original ResearchConceptsDriver genesRisk genesCritical cellular functionsDeeper molecular insightsDivergent genesPhenotypic variationCellular functionsTranscriptome perturbationsGene embeddingsGCN analysisGene prioritizationPathway levelDifferent genesGene classificationMolecular insightsGenesNetwork modulesComplex networksDifferent diseasesHierarchical levelsCellsIntegrating genetics and transcriptomics to study major depressive disorder: a conceptual framework, bioinformatic approaches, and recent findings
Hicks E, Seah C, Cote A, Marchese S, Brennand K, Nestler E, Girgenti M, Huckins L. Integrating genetics and transcriptomics to study major depressive disorder: a conceptual framework, bioinformatic approaches, and recent findings. Translational Psychiatry 2023, 13: 129. PMID: 37076454, PMCID: PMC10115809, DOI: 10.1038/s41398-023-02412-7.Peer-Reviewed Original ResearchConceptsBioinformatics approachTranscriptomic dataBrain transcriptomeGenome-wide analysisDynamic transcriptional landscapeBrain gene expression dataGene expression dataTranscriptional landscapeTranscriptomic studiesIntegrating GeneticExpression dataPhenotypic signaturesGenomic driversTranscriptomeMajor depressive disorderValuable resourceRecent findingsEnvironmental influencesTranscriptomicsDepressive disorderGeneticsMultiple approachesPathophysiology of depressionSignaturesDysregulation
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
Stress 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 disorderPTSD 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
2017
Molecular 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 evidencePTSDPatients
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