2024
Somatic mosaicism in schizophrenia brains reveals prenatal mutational processes
Maury E, Jones A, Seplyarskiy V, Nguyen T, Rosenbluh C, Bae T, Wang Y, Abyzov A, Khoshkhoo S, Chahine Y, Zhao S, Venkatesh S, Root E, Voloudakis G, Roussos P, Network B, Park P, Akbarian S, Brennand K, Reilly S, Lee E, Sunyaev S, Walsh C, Chess A. Somatic mosaicism in schizophrenia brains reveals prenatal mutational processes. Science 2024, 386: 217-224. PMID: 39388546, PMCID: PMC11490355, DOI: 10.1126/science.adq1456.Peer-Reviewed Original ResearchConceptsTranscription factor binding sitesWhole-genome sequencingOpen chromatinMutational processesSomatic mutationsFactor binding sitesSchizophrenia casesSchizophrenia risk genesSomatic mosaicismSomatic variantsRisk genesG mutationGene expressionGermline mutationsBinding sitesGenesMutationsIncreased somatic mutationsChromatinMosaic somatic mutationsPrenatal neurogenesisContext of schizophreniaBrain neuronsSchizophrenia brainVariantsSingle-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 tissuesExpressionCellsChromatinLociMultiomicsCharacterization of enhancer activity in early human neurodevelopment using Massively Parallel Reporter Assay (MPRA) and forebrain organoids
Capauto D, Wang Y, Wu F, Norton S, Mariani J, Inoue F, Crawford G, Ahituv N, Abyzov A, Vaccarino F. Characterization of enhancer activity in early human neurodevelopment using Massively Parallel Reporter Assay (MPRA) and forebrain organoids. Scientific Reports 2024, 14: 3936. PMID: 38365907, PMCID: PMC10873509, DOI: 10.1038/s41598-024-54302-7.Peer-Reviewed Original ResearchConceptsMassively parallel reporter assaysGene expressionRegulation of gene expressionForebrain organoidsHuman fetal tissuesHigh-throughput assayReporter assayFetal tissuesStem cellsNeurodevelopmentHuman neurodevelopmentActivation signalsEnhanced activityGenesOrganoidsForebrainBrain organoidsAssayBrain
2020
Chapter 5 Induced pluripotent stem cells as models of human neurodevelopmental disorders
Jourdon A, Mariani J, Scuderi S, Amiri A, Wu F, Yuen E, Abyzov A, Vaccarino F. Chapter 5 Induced pluripotent stem cells as models of human neurodevelopmental disorders. 2020, 99-127. DOI: 10.1016/b978-0-12-814409-1.00005-7.ChaptersPluripotent stem cellsStem cellsStudy of speciesHuman neurodevelopmental disordersEpigenome analysisGene regulationIPSC fieldGenomic variationGene expressionGenetic backgroundDisease modelingStudies of neurodevelopmentIPSCsExperimental approachNeurodevelopmental disordersTranscriptomeGenomeCellsCell phenotypingSpeciesExperimental design issuesPhenotypeRegulationExpressionPhenotyping
2011
Integration of protein motions with molecular networks reveals different mechanisms for permanent and transient interactions
Bhardwaj N, Abyzov A, Clarke D, Shou C, Gerstein MB. Integration of protein motions with molecular networks reveals different mechanisms for permanent and transient interactions. Protein Science 2011, 20: 1745-1754. PMID: 21826754, PMCID: PMC3218368, DOI: 10.1002/pro.710.Peer-Reviewed Original ResearchConceptsMulti-interface hubsMolecular networksConformational changesInteraction networksTransient interactionsStructural interaction networksProtein interaction networksClassification of proteinsDynamic conformational changesProtein structural featuresSmall conformational changesTransient associationGene expressionMore plasticityProtein motionsStructural databankProteinAlternate conformationDifferent mechanismsDrastic structural changesDomainInteraction