2024
42. STRESS EXPOSURE DYNAMICALLY REGULATES EQTL ACTIVITY IN THE POST-MORTEM BRAIN AND IN HIPSC-DERIVED NEURONS
Seah C, Signer R, Young H, Hicks E, Rusielewicz T, Bader H, Xu C, Breen M, Paull D, Yehuda R, Girgenti M, Brennand K, Huckins L. 42. STRESS EXPOSURE DYNAMICALLY REGULATES EQTL ACTIVITY IN THE POST-MORTEM BRAIN AND IN HIPSC-DERIVED NEURONS. European Neuropsychopharmacology 2024, 87: 71-72. DOI: 10.1016/j.euroneuro.2024.08.156.Peer-Reviewed Original ResearchPost-mortem brainsTranscription factor binding sitesAbsence of cellular stressCombat-exposed veteransFactor binding sitesImpact gene expressionBinding sitesGR binding sitesPositive regulatory activityMotif enrichmentSequence readsCRISPRi screenOpen chromatinFunctional annotationBrain regionsTraumatic stressCRISPR screensEQTLTraumatic experiencesLeading locusPTSDPerturbed genesRegulatory architectureTranscriptomic activityTranscriptomic responseSingle-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 tissuesExpressionCellsChromatinLociMultiomics361. Imaging HDAC6 in PTSD
Bonomi R, Girgenti M, Cosgrove K. 361. Imaging HDAC6 in PTSD. Biological Psychiatry 2024, 95: s247. DOI: 10.1016/j.biopsych.2024.02.860.Peer-Reviewed Original ResearchThe Prefrontal Cortex Transcriptomic Landscape of the Comorbidity Between Post-Traumatic Stress Disorder and Opioid Misuse
Martinez-Magaña J, Nagamatsu S, Nunez-Rios D, Krystal J, Girgenti M, Group T, Montalvo-Ortiz J. The Prefrontal Cortex Transcriptomic Landscape of the Comorbidity Between Post-Traumatic Stress Disorder and Opioid Misuse. Biological Psychiatry 2024, 95: s69. DOI: 10.1016/j.biopsych.2024.02.169.Peer-Reviewed Original Research209 Transcriptomic Analysis of the Post-mortem Brain in Intracranial Atherosclerosis Implicates Interferon Signaling
Seah C, Devarajan A, Jurczyszak D, Chakka A, Huckins L, Brennand K, Girgenti M. 209 Transcriptomic Analysis of the Post-mortem Brain in Intracranial Atherosclerosis Implicates Interferon Signaling. Neurosurgery 2024, 70: 55-56. DOI: 10.1227/neu.0000000000002809_209.Peer-Reviewed Original ResearchIntracranial atherosclerotic stenosisIntracranial arteriesInterferon-inducible genesInterferon signalingPeripheral atherosclerosisCerebral atherosclerosisExpression of interferon-inducible genesGlial cellsSymptomatic intracranial atherosclerotic stenosisInduced pluripotent stem cellsPost-mortem brainsWorsened functional outcomesHuman induced pluripotent stem cellsUpregulation of interferon inducible genesCause of ischemic strokePluripotent stem cellsRisk of atherosclerosisLipid-rich plaquesRisk factor managementClinical outcomesPoor prognosisExcitatory neuronsIncreased morbidityHistopathological profileFunctional outcomesscENCORE: leveraging single-cell epigenetic data to predict chromatin conformation using graph embedding
Duan Z, Xu S, Srinivasan S, Hwang A, Lee C, Yue F, Gerstein M, Luan Y, Girgenti M, Zhang J. scENCORE: leveraging single-cell epigenetic data to predict chromatin conformation using graph embedding. Briefings In Bioinformatics 2024, 25: bbae096. PMID: 38493342, PMCID: PMC10944576, DOI: 10.1093/bib/bbae096.Peer-Reviewed Original ResearchConceptsA/B compartmentsEpigenetic dataChromatin interaction frequenciesCell type-specific mannerChromatin conformational changesGenome binsGenomic regionsChromatin conformationEukaryotic DNAChromatin compartmentsDynamic compartmentalizationRepressed stateGenetic blueprintTranscriptional programsTranscriptional changesChromatinConformational changesComplex tissuesInteraction frequencyCompartmentGenomeChromosomeStructural heterogeneityDNAA/BTuning 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
2023
Novel hippocampal genes involved in enhanced susceptibility to chronic pain-induced behavioral emotionality
Garman A, Ash A, Kokkinos E, Nerland D, Winter L, Langreck C, Forgette M, Girgenti M, Banasr M, Duric V. Novel hippocampal genes involved in enhanced susceptibility to chronic pain-induced behavioral emotionality. European Journal Of Pharmacology 2023, 964: 176273. PMID: 38135263, DOI: 10.1016/j.ejphar.2023.176273.Peer-Reviewed Original ResearchBlood-brain barrier integrityChronic pain statesBehavioral emotionalityHippocampal genesPain statesGenome-wide RNA-seq analysisStress responseBarrier integrityCommon stress responseRNA-seq analysisAurora kinase BChronic inflammatory painDepressive-like behaviorChronic pain conditionsRodent stress modelsLimbic brain regionsTight junction proteinsBioinformatics analysisInflammatory painAstrocyte activationPain groupPain conditionsTranscriptomic profilesAltered moodKinase BUncommon Protein-Coding Variants Associated With Suicide Attempt in a Diverse Sample of U.S. Army Soldiers
Wilkerson M, Hupalo D, Gray J, Zhang X, Wang J, Girgenti M, Alba C, Sukumar G, Lott N, Naifeh J, Aliaga P, Kessler R, Turner C, Pollard H, Dalgard C, Ursano R, Stein M. Uncommon Protein-Coding Variants Associated With Suicide Attempt in a Diverse Sample of U.S. Army Soldiers. Biological Psychiatry 2023, 96: 15-25. PMID: 38141912, DOI: 10.1016/j.biopsych.2023.12.008.Peer-Reviewed Original ResearchSingle variant analysisProtein-coding variantsVariant analysisCommon genetic variantsWhole-genome sequencingMost genesWhole genomeGenome sequencingSignificant genesMolecular characterizationGenesGenetic variantsAncestry groupsGenetic risk factorsExomeYWHAERecent studiesVariantsATAD3ARC3H2EP400GenomeRcn2SGMS1STARD9
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 humansGenesPrimatesTranslator: A Transfer Learning Approach to Facilitate Single-Cell ATAC-Seq Data Analysis from Reference Dataset
Xu S, Skarica M, Hwang A, Dai Y, Lee C, Girgenti MJ, Zhang J. Translator: A Transfer Learning Approach to Facilitate Single-Cell ATAC-Seq Data Analysis from Reference Dataset. Journal Of Computational Biology 2022, 29: 619-633. PMID: 35584295, PMCID: PMC9464368, DOI: 10.1089/cmb.2021.0596.Peer-Reviewed Original ResearchConceptsGraphic Processing Units ParallelismComplex feature interactionsDeep learning frameworkFree software packageFeature interactionsUltra-high dimensionalityLearning frameworkSoftware packageComputational efficiencySeq data analysisScATAC-seq dataDatasetReference datasetReference dataData analysisDownstream analysisCell representationRepresentationParallelismLow signalTranslatorsClusteringDimensionalityNoise ratioNonlinear relationshipPositive modulation of N-methyl-D-aspartate receptors in the mPFC reduces the spontaneous recovery of fear
Lee B, Pothula S, Wu M, Kang H, Girgenti MJ, Picciotto MR, DiLeone RJ, Taylor JR, Duman RS. Positive modulation of N-methyl-D-aspartate receptors in the mPFC reduces the spontaneous recovery of fear. Molecular Psychiatry 2022, 27: 2580-2589. PMID: 35418600, PMCID: PMC9135632, DOI: 10.1038/s41380-022-01498-7.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderFear extinctionInfralimbic medial prefrontal cortexFear conditioning modelEnhanced fear extinctionFear-based behaviorsProlonged stress modelMedial prefrontal cortexSpontaneous recoveryIL-mPFCPTSD modelPTSD treatmentStress disorderPrefrontal cortexSPS modelN-methyl-D-aspartate receptor modulatorsBrain-derived neurotrophic factorN-methyl-D-aspartate receptorsBehavioral effectsIncreased attentionMPFCPreclinical findingsPyramidal neuronsNeurotrophic factorMale miceMatthew 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 ResearchInsuLock: A Weakly Supervised Learning Approach for Accurate Insulator Prediction, and Variant Impact Quantification
Srinivasan S, Gong Y, Xu S, Hwang A, Xu M, Girgenti M, Zhang J. InsuLock: A Weakly Supervised Learning Approach for Accurate Insulator Prediction, and Variant Impact Quantification. Genes 2022, 13: 621. PMID: 35456427, PMCID: PMC9026820, DOI: 10.3390/genes13040621.Peer-Reviewed Original ResearchA Role for Histone Deacetylases in the Biology and Treatment of Post-Traumatic Stress Disorder: What Do We Know and Where Do We Go from Here?
Bonomi R, Girgenti M, Krystal J, Cosgrove K. A Role for Histone Deacetylases in the Biology and Treatment of Post-Traumatic Stress Disorder: What Do We Know and Where Do We Go from Here? Complex Psychiatry 2022, 8: 13-27. PMID: 36545044, PMCID: PMC9669946, DOI: 10.1159/000524079.Peer-Reviewed Original Research
2021
Transcriptomics of the depressed and PTSD brain
Zhang J, Kaye AP, Wang J, Girgenti MJ. Transcriptomics of the depressed and PTSD brain. Neurobiology Of Stress 2021, 15: 100408. PMID: 34703849, PMCID: PMC8524242, DOI: 10.1016/j.ynstr.2021.100408.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsHigh-throughput transcriptomic methodsSingle-cell RNA sequencingCell RNA sequencingLarge genomic datasetsCommon molecular pathwaysTranscriptomic approachTranscriptional programsTranscriptome studiesStress adaptationTranscriptomic methodsRNA sequencingGenomic datasetsSurvival mechanismMolecular pathwaysOrganismsPTSD brainsTranscriptomeTranscriptomicsAdaptationNeurobiology of stressStressSequencingPathwayCentral questionNeurobiologistsGene expression in the dorsolateral and ventromedial prefrontal cortices implicates immune-related gene networks in PTSD
Logue MW, Zhou Z, Morrison FG, Wolf EJ, Daskalakis NP, Chatzinakos C, Georgiadis F, Labadorf AT, Girgenti MJ, Young KA, Williamson DE, Zhao X, Grenier JG, Group T, Huber BR, Miller MW. Gene expression in the dorsolateral and ventromedial prefrontal cortices implicates immune-related gene networks in PTSD. Neurobiology Of Stress 2021, 15: 100398. PMID: 34646915, PMCID: PMC8498459, DOI: 10.1016/j.ynstr.2021.100398.Peer-Reviewed Original ResearchPrefrontal cortexVentromedial prefrontal cortexDepression casesHistory of PTSDDepression-associated genesImmune-related networkBrain BankImmune regulationGene expressionIndependent cohortBrain regionsEvidence of replicationPTSD casesMultiple testing correctionImmune genesPTSDCo-expression network analysisCortexEffect sizeUpstream regulatorRNA sequencingRecent studiesGenetic modelsExpressionCandidate gene analysisPosttraumatic 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