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 brainVariantsCross-ancestry atlas of gene, isoform, and splicing regulation in the developing human brain
Wen C, Margolis M, Dai R, Zhang P, Przytycki P, Vo D, Bhattacharya A, Matoba N, Tang M, Jiao C, Kim M, Tsai E, Hoh C, Aygün N, Walker R, Chatzinakos C, Clarke D, Pratt H, Peters M, Gerstein M, Daskalakis N, Weng Z, Jaffe A, Kleinman J, Hyde T, Weinberger D, Bray N, Sestan N, Geschwind D, Roeder K, Gusev A, Pasaniuc B, Stein J, Love M, Pollard K, Liu C, Gandal M, Akbarian S, Abyzov A, Ahituv N, Arasappan D, Almagro Armenteros J, Beliveau B, Bendl J, Berretta S, Bharadwaj R, Bicks L, Brennand K, Capauto D, Champagne F, Chatterjee T, Chatzinakos C, Chen Y, Chen H, Cheng Y, Cheng L, Chess A, Chien J, Chu Z, Clement A, Collado-Torres L, Cooper G, Crawford G, Davila-Velderrain J, Deep-Soboslay A, Deng C, DiPietro C, Dracheva S, Drusinsky S, Duan Z, Duong D, Dursun C, Eagles N, Edelstein J, Emani P, Fullard J, Galani K, Galeev T, Gaynor S, Girdhar K, Goes F, Greenleaf W, Grundman J, Guo H, Guo Q, Gupta C, Hadas Y, Hallmayer J, Han X, Haroutunian V, Hawken N, He C, Henry E, Hicks S, Ho M, Ho L, Hoffman G, Huang Y, Huuki-Myers L, Hwang A, Iatrou A, Inoue F, Jajoo A, Jensen M, Jiang L, Jin P, Jin T, Jops C, Jourdon A, Kawaguchi R, Kellis M, Kleopoulos S, Kozlenkov A, Kriegstein A, Kundaje A, Kundu S, Lee C, Lee D, Li J, Li M, Lin X, Liu S, Liu J, Liu J, Liu S, Lou S, Loupe J, Lu D, Ma S, Ma L, Mariani J, Martinowich K, Maynard K, Mazariegos S, Meng R, Myers R, Micallef C, Mikhailova T, Ming G, Mohammadi S, Monte E, Montgomery K, Moore J, Moran J, Mukamel E, Nairn A, Nemeroff C, Ni P, Norton S, Nowakowski T, Omberg L, Page S, Park S, Patowary A, Pattni R, Pertea G, Phalke N, Pinto D, Pjanic M, Pochareddy S, Pollen A, Purmann C, Qin Z, Qu P, Quintero D, Raj T, Rajagopalan A, Reach S, Reimonn T, Ressler K, Ross D, Roussos P, Rozowsky J, Ruth M, Ruzicka W, Sanders S, Schneider J, Scuderi S, Sebra R, Seyfried N, Shao Z, Shedd N, Shieh A, Shin J, Skarica M, Snijders C, Song H, State M, Steyert M, Subburaju S, Sudhof T, Snyder M, Tao R, Therrien K, Tsai L, Urban A, Vaccarino F, van Bakel H, Voloudakis G, Wamsley B, Wang T, Wang S, Wang D, Wang Y, Warrell J, Wei Y, Weimer A, Whalen S, White K, Willsey A, Won H, Wong W, Wu H, Wu F, Wuchty S, Wylie D, Xu S, Yap C, Zeng B, Zhang C, Zhang B, Zhang J, Zhang Y, Zhou X, Ziffra R, Zeier Z, Zintel T. Cross-ancestry atlas of gene, isoform, and splicing regulation in the developing human brain. Science 2024, 384: eadh0829. PMID: 38781368, DOI: 10.1126/science.adh0829.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide association study lociSplicing quantitative trait lociQuantitative trait lociSplicing regulationCross-ancestryTrait lociAssociation studiesRegulatory elementsCellular contextHuman brainTranscriptome regulationCoexpression networkRisk genesAutism spectrum disorderGenesCellular heterogeneityComprehensive landscapeSpectrum disorderIsoformsSplicingIncreased cellular heterogeneityLociNeuronal maturationRegulationSingle-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 tissuesExpressionCellsChromatinLociMultiomics
2023
Genomic data resources of the Brain Somatic Mosaicism Network for neuropsychiatric diseases
Garrison M, Jang Y, Bae T, Cherskov A, Emery S, Fasching L, Jones A, Moldovan J, Molitor C, Pochareddy S, Peters M, Shin J, Wang Y, Yang X, Akbarian S, Chess A, Gage F, Gleeson J, Kidd J, McConnell M, Mills R, Moran J, Park P, Sestan N, Urban A, Vaccarino F, Walsh C, Weinberger D, Wheelan S, Abyzov A. Genomic data resources of the Brain Somatic Mosaicism Network for neuropsychiatric diseases. Scientific Data 2023, 10: 813. PMID: 37985666, PMCID: PMC10662356, DOI: 10.1038/s41597-023-02645-7.Peer-Reviewed Original ResearchComprehensive multi-omic profiling of somatic mutations in malformations of cortical development
Chung C, Yang X, Bae T, Vong K, Mittal S, Donkels C, Westley Phillips H, Li Z, Marsh A, Breuss M, Ball L, Garcia C, George R, Gu J, Xu M, Barrows C, James K, Stanley V, Nidhiry A, Khoury S, Howe G, Riley E, Xu X, Copeland B, Wang Y, Kim S, Kang H, Schulze-Bonhage A, Haas C, Urbach H, Prinz M, Limbrick D, Gurnett C, Smyth M, Sattar S, Nespeca M, Gonda D, Imai K, Takahashi Y, Chen H, Tsai J, Conti V, Guerrini R, Devinsky O, Silva W, Machado H, Mathern G, Abyzov A, Baldassari S, Baulac S, Gleeson J. Comprehensive multi-omic profiling of somatic mutations in malformations of cortical development. Nature Genetics 2023, 55: 209-220. PMID: 36635388, PMCID: PMC9961399, DOI: 10.1038/s41588-022-01276-9.Peer-Reviewed Original ResearchConceptsSingle-nucleus RNA sequencingSpatiotemporal expression patternsSomatic mutationsTarget amplicon sequencingLow allelic fractionsMulti-omics profilingGene setsRNA sequencingFunctional validationCellular organizationExpression patternsGenotype-phenotype correlation analysisGenetic landscapeCortical developmentMutationsGenetic causeUtero electroporationSomatic mosaic mutationsGenesCritical roleMosaic mutationsSequencingNeuronal hyperexcitabilityBrain resectionProfiling
2022
Somatic genomic mosaicism in the brain during aging: Scratching the surface
Bae T, Wang Y, Vaccarino F, Abyzov A. Somatic genomic mosaicism in the brain during aging: Scratching the surface. Clinical And Translational Medicine 2022, 12: e1138. PMID: 36495113, PMCID: PMC9736788, DOI: 10.1002/ctm2.1138.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsAnalysis of somatic mutations in 131 human brains reveals aging-associated hypermutability
Bae T, Fasching L, Wang Y, Shin JH, Suvakov M, Jang Y, Norton S, Dias C, Mariani J, Jourdon A, Wu F, Panda A, Pattni R, Chahine Y, Yeh R, Roberts RC, Huttner A, Kleinman JE, Hyde TM, Straub RE, Walsh CA, Urban A, Leckman J, Weinberger D, Vaccarino F, Abyzov A, Walsh C, Park P, Sestan N, Weinberger D, Moran J, Gage F, Vaccarino F, Gleeson J, Mathern G, Courchesne E, Roy S, Chess A, Akbarian S, Bizzotto S, Coulter M, Dias C, D’Gama A, Ganz J, Hill R, Huang A, Khoshkhoo S, Kim S, Lee A, Lodato M, Maury E, Miller M, Borges-Monroy R, Rodin R, Zhou Z, Bohrson C, Chu C, Cortes-Ciriano I, Dou Y, Galor A, Gulhan D, Kwon M, Luquette J, Sherman M, Viswanadham V, Jones A, Rosenbluh C, Cho S, Langmead B, Thorpe J, Erwin J, Jaffe A, McConnell M, Narurkar R, Paquola A, Shin J, Straub R, Abyzov A, Bae T, Jang Y, Wang Y, Molitor C, Peters M, Linker S, Reed P, Wang M, Urban A, Zhou B, Zhu X, Pattni R, Serres Amero A, Juan D, Lobon I, Marques-Bonet T, Solis Moruno M, Garcia Perez R, Povolotskaya I, Soriano E, Antaki D, Averbuj D, Ball L, Breuss M, Yang X, Chung C, Emery S, Flasch D, Kidd J, Kopera H, Kwan K, Mills R, Moldovan J, Sun C, Zhao X, Zhou W, Frisbie T, Cherskov A, Fasching L, Jourdon A, Pochareddy S, Scuderi S. Analysis of somatic mutations in 131 human brains reveals aging-associated hypermutability. Science 2022, 377: 511-517. PMID: 35901164, PMCID: PMC9420557, DOI: 10.1126/science.abm6222.Peer-Reviewed Original ResearchConceptsTranscription factorsSomatic mutationsPutative transcription factorEnhancer-like regionSingle nucleotide mutationsWhole-genome sequencingGene regulationSomatic duplicationGenome sequencingDamaging mutationsBackground mutagenesisMutationsHypermutabilityClonal expansionMotifDiseased brainPotential linkVivo clonal expansionMutagenesisGenesDuplicationSequencingRegulation
2021
Comprehensive identification of somatic nucleotide variants in human brain tissue
Wang Y, Bae T, Thorpe J, Sherman MA, Jones AG, Cho S, Daily K, Dou Y, Ganz J, Galor A, Lobon I, Pattni R, Rosenbluh C, Tomasi S, Tomasini L, Yang X, Zhou B, Akbarian S, Ball LL, Bizzotto S, Emery SB, Doan R, Fasching L, Jang Y, Juan D, Lizano E, Luquette LJ, Moldovan JB, Narurkar R, Oetjens MT, Rodin RE, Sekar S, Shin JH, Soriano E, Straub RE, Zhou W, Chess A, Gleeson JG, Marquès-Bonet T, Park PJ, Peters MA, Pevsner J, Walsh CA, Weinberger DR, Vaccarino F, Moran J, Urban A, Kidd J, Mills R, Abyzov A. Comprehensive identification of somatic nucleotide variants in human brain tissue. Genome Biology 2021, 22: 92. PMID: 33781308, PMCID: PMC8006362, DOI: 10.1186/s13059-021-02285-3.Peer-Reviewed Original ResearchConceptsSomatic SNVsSomatic single nucleotide variantsWhole-genome sequencing dataSequencing dataBulk DNA samplesCell lineage treesSomatic mosaicismSingle nucleotide variantsLineage treesSomatic nucleotide variantsCellular processesDNA replicationHuman genomeSomatic tissuesDNA repairNucleotide variantsComprehensive identificationDNA samplesMosaic variantsNon-cancerous tissuesDNASingle individualMultiple replicatesHuman brain tissueVariants
2020
Complex mosaic structural variations in human fetal brains
Sekar S, Tomasini L, Proukakis C, Bae T, Manlove L, Jang Y, Scuderi S, Zhou B, Kalyva M, Amiri A, Mariani J, Sedlazeck F, Urban AE, Vaccarino F, Abyzov A. Complex mosaic structural variations in human fetal brains. Genome Research 2020, 30: gr.262667.120. PMID: 33122304, PMCID: PMC7706730, DOI: 10.1101/gr.262667.120.Peer-Reviewed Original ResearchConceptsSingle nucleotide variantsCopy number variantsStructural variantsMegabase-scale copy number variantsHuman fetal brainFunctional consequencesMobile element insertionsSimilar functional consequencesFetal brainMosaic single-nucleotide variantsAdult brain neuronsStructural variationsPotential functional consequencesKilobase scaleDNA eventsGenomic fragmentDifferent chromosomesElement insertionsClonal approachHuman brain cellsFetal human brainNucleotide variantsReplication errorsHuman brainNumber variants
2017
Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network
McConnell MJ, Moran JV, Abyzov A, Akbarian S, Bae T, Cortes-Ciriano I, Erwin JA, Fasching L, Flasch DA, Freed D, Ganz J, Jaffe AE, Kwan KY, Kwon M, Lodato MA, Mills RE, Paquola ACM, Rodin RE, Rosenbluh C, Sestan N, Sherman MA, Shin JH, Song S, Straub RE, Thorpe J, Weinberger DR, Urban AE, Zhou B, Gage FH, Lehner T, Senthil G, Walsh CA, Chess A, Courchesne E, Gleeson JG, Kidd JM, Park PJ, Pevsner J, Vaccarino FM, Barton A, Bekiranov S, Bohrson C, Burbulis I, Chronister W, Coppola G, Daily K, D’Gama A, Emery S, Frisbie T, Gao T, Gulyás-Kovács A, Haakenson M, Keil J, Kopera H, Lam M, Lee E, Marques-Bonet T, Mathern G, Moldovan J, Oetjens M, Omberg L, Peters M, Pochareddy S, Pramparo T, Ratan A, Sanavia T, Shi L, Skarica M, Wang J, Wang M, Wang Y, Wierman M, Wolpert M, Woodworth M, Zhao X, Zhou W. Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network. Science 2017, 356 PMID: 28450582, PMCID: PMC5558435, DOI: 10.1126/science.aal1641.Peer-Reviewed Original ResearchConceptsSomatic mutationsComplex genetic architectureStructural genomic variantsNeuronal genomeNeuronal transcriptomeGenetic architectureCell divisionCellular metabolismGenomic variantsLong life spanDNA damageComplex neuropsychiatric disorderCellular expansionNeuropsychiatric diseasesNeuropsychiatric disordersProgenitor cellsSomatic mosaicismIndividual neurodevelopmentSmall populationCell proliferationPopulation-based studyMutationsGermline variantsLife spanBrain developmentHuman induced pluripotent stem cells for modelling neurodevelopmental disorders
Ardhanareeswaran K, Mariani J, Coppola G, Abyzov A, Vaccarino FM. Human induced pluripotent stem cells for modelling neurodevelopmental disorders. Nature Reviews Neurology 2017, 13: 265-278. PMID: 28418023, PMCID: PMC5782822, DOI: 10.1038/nrneurol.2017.45.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsEmbryonic stem cellsNeurodevelopmental disordersPluripotent stem cellsBrain developmentStem cellsAbnormal brain developmentBrain cell typesDopaminergic neuronsCortical neuronsUnique genetic signatureEarly developmentKey PointsHumanHiPSC modelsSomatic cellsDisordersGenetic signaturesGenetic studiesAltered trajectoryCell typesAdult cellsNeuronsUnknown facetsCellsDrug discoveryHiPSCs
2015
The PsychENCODE project
Akbarian S, Liu C, Knowles JA, Vaccarino FM, Farnham PJ, Crawford GE, Jaffe AE, Pinto D, Dracheva S, Geschwind DH, Mill J, Nairn AC, Abyzov A, Pochareddy S, Prabhakar S, Weissman S, Sullivan PF, State MW, Weng Z, Peters MA, White KP, Gerstein MB, Amiri A, Armoskus C, Ashley-Koch AE, Bae T, Beckel-Mitchener A, Berman BP, Coetzee GA, Coppola G, Francoeur N, Fromer M, Gao R, Grennan K, Herstein J, Kavanagh DH, Ivanov NA, Jiang Y, Kitchen RR, Kozlenkov A, Kundakovic M, Li M, Li Z, Liu S, Mangravite LM, Mattei E, Markenscoff-Papadimitriou E, Navarro FC, North N, Omberg L, Panchision D, Parikshak N, Poschmann J, Price AJ, Purcaro M, Reddy TE, Roussos P, Schreiner S, Scuderi S, Sebra R, Shibata M, Shieh AW, Skarica M, Sun W, Swarup V, Thomas A, Tsuji J, van Bakel H, Wang D, Wang Y, Wang K, Werling DM, Willsey AJ, Witt H, Won H, Wong CC, Wray GA, Wu EY, Xu X, Yao L, Senthil G, Lehner T, Sklar P, Sestan N. The PsychENCODE project. Nature Neuroscience 2015, 18: 1707-1712. PMID: 26605881, PMCID: PMC4675669, DOI: 10.1038/nn.4156.Peer-Reviewed Original Research