2024
Massively parallel characterization of regulatory elements in the developing human cortex
Deng C, Whalen S, Steyert M, Ziffra R, Przytycki P, Inoue F, Pereira D, Capauto D, Norton S, Vaccarino F, Pollen A, Nowakowski T, Ahituv N, Pollard K, Akbarian S, Abyzov A, Ahituv N, Arasappan D, Almagro Armenteros J, Beliveau B, Bendl J, Berretta S, Bharadwaj R, Bhattacharya A, 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, Clarke D, 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, Duan Z, Duong D, Dursun C, Eagles N, Edelstein J, Emani P, Fullard J, Galani K, Galeev T, Gandal M, Gaynor S, Gerstein M, Geschwind D, 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, Hyde T, Iatrou A, Inoue F, Jajoo A, Jensen M, Jiang L, Jin P, Jin T, Jops C, Jourdon A, Kawaguchi R, Kellis M, Khullar S, Kleinman J, 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 C, Liu S, Lou S, Loupe J, Lu D, Ma S, Ma L, Margolis M, 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, Peters M, Phalke N, Pinto D, Pjanic M, Pochareddy S, Pollard K, Pollen A, Pratt H, Przytycki P, 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, Sestan N, Seyfried N, Shao Z, Shedd N, 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, Wamsley B, Wang T, Wang S, Wang D, Wang Y, Warrell J, Wei Y, Weimer A, Weinberger D, Wen C, Weng Z, 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 P, Zhang C, Zhang B, Zhang J, Zhang Y, Zhou X, Ziffra R, Zeier Z, Zintel T. Massively parallel characterization of regulatory elements in the developing human cortex. Science 2024, 384: eadh0559. PMID: 38781390, DOI: 10.1126/science.adh0559.Peer-Reviewed Original ResearchMeSH KeywordsCerebral CortexChromatinDeep LearningEnhancer Elements, GeneticGene Expression Regulation, DevelopmentalHumansNeurogenesisNeuronsOrganoidsRegulatory Sequences, Nucleic AcidConceptsGene regulatory elementsRegulatory elementsRegulation of enhancer activityCharacterization of regulatory elementsCis-regulatory activityNeuronal developmentPrimary cellsEnhanced activityGene regulationHuman neuronal developmentNucleotide changesEnhancer sequencesSequence basisUpstream regulatorComprehensive catalogHuman cellsDeveloping cortexSequenceVariantsOrganoidsCellsCerebral organoidsCortexHuman cortexNucleotideCharacterization 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 ResearchMeSH KeywordsEnhancer Elements, GeneticGene Expression RegulationHumansOrganoidsProsencephalonRegulatory Sequences, Nucleic AcidConceptsMassively parallel reporter assaysGene expressionRegulation of gene expressionForebrain organoidsHuman fetal tissuesHigh-throughput assayReporter assayFetal tissuesStem cellsNeurodevelopmentHuman neurodevelopmentActivation signalsEnhanced activityGenesOrganoidsForebrainBrain organoidsAssayBrain
2022
Analysis 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 ResearchMeSH KeywordsAgingAutistic DisorderBrainEnhancer Elements, GeneticGene Expression RegulationHumansMutagenesisMutationProtein BindingTranscription FactorsWhole Genome SequencingConceptsTranscription factorsSomatic mutationsPutative transcription factorEnhancer-like regionSingle nucleotide mutationsWhole-genome sequencingGene regulationSomatic duplicationGenome sequencingDamaging mutationsBackground mutagenesisMutationsHypermutabilityClonal expansionMotifDiseased brainPotential linkVivo clonal expansionMutagenesisGenesDuplicationSequencingRegulation
2018
Transcriptome and epigenome landscape of human cortical development modeled in organoids
Amiri A, Coppola G, Scuderi S, Wu F, Roychowdhury T, Liu F, Pochareddy S, Shin Y, Safi A, Song L, Zhu Y, Sousa AMM, Gerstein M, Crawford G, Sestan N, Abyzov A, Vaccarino F, Akbarian S, An J, Armoskus C, Ashley-Koch A, Beach T, Belmont J, Bendl J, Borrman T, Brown L, Brown M, Brown M, Brunetti T, Bryois J, Burke E, Camarena A, Carlyle B, Chae Y, Charney A, Chen C, Cheng L, Cherskov A, Choi J, Clarke D, Collado-Torres L, Dai R, De La Torre Ubieta L, DelValle D, Devillers O, Dracheva S, Emani P, Evgrafov O, Farnham P, Fitzgerald D, Flatow E, Francoeur N, Fullard J, Gandal M, Gao T, Garrett M, Geschwind D, Giase G, Girdhar K, Giusti-Rodriguez P, Goes F, Goodman T, Grennan K, Gu M, Gürsoy G, Hadjimichael E, Hahn C, Haroutunian V, Hauberg M, Hoffman G, Huey J, Hyde T, Ivanov N, Jacobov R, Jaffe A, Jiang Y, Jiang Y, Johnson G, Kassim B, Kefi A, Kim Y, Kitchen R, Kleiman J, Knowles J, Kozlenkov A, Li M, Li Z, Lipska B, Liu C, Liu S, Mangravite L, Mariani J, Mattei E, Miller D, Moore J, Nairn A, Navarro F, Park R, Peters M, Pinto D, Pochareddy S, Polioudakis D, Pratt H, Price A, Purcaro M, Ray M, Reddy T, Rhie S, Roussos P, Sanders S, Santpere G, Schreiner S, Sheppard B, Shi X, Shieh A, Shin J, Skarica M, Song L, Sousa A, Spitsyna V, State M, Sullivan P, Swarup V, Szatkiewicz J, Szekely A, Tao R, van Bakel H, Wang Y, Wang D, Warrell J, Webster M, Weissman S, Weng Z, Werling D, White K, Willsey J, Wiseman J, Witt H, Won H, Wray G, Xia Y, Xu M, Yang Y, Yang M, Zandi P, Zhang J, Zharovsky E. Transcriptome and epigenome landscape of human cortical development modeled in organoids. Science 2018, 362 PMID: 30545853, PMCID: PMC6426303, DOI: 10.1126/science.aat6720.Peer-Reviewed Original ResearchComprehensive functional genomic resource and integrative model for the human brain
Wang D, Liu S, Warrell J, Won H, Shi X, Navarro FCP, Clarke D, Gu M, Emani P, Yang YT, Xu M, Gandal MJ, Lou S, Zhang J, Park JJ, Yan C, Rhie SK, Manakongtreecheep K, Zhou H, Nathan A, Peters M, Mattei E, Fitzgerald D, Brunetti T, Moore J, Jiang Y, Girdhar K, Hoffman GE, Kalayci S, Gümüş ZH, Crawford GE, Roussos P, Akbarian S, Jaffe A, White K, Weng Z, Sestan N, Geschwind D, Knowles J, Gerstein M, Ashley-Koch A, Crawford G, Garrett M, Song L, Safi A, Johnson G, Wray G, Reddy T, Goes F, Zandi P, Bryois J, Jaffe A, Price A, Ivanov N, Collado-Torres L, Hyde T, Burke E, Kleiman J, Tao R, Shin J, Akbarian S, Girdhar K, Jiang Y, Kundakovic M, Brown L, Kassim B, Park R, Wiseman J, Zharovsky E, Jacobov R, Devillers O, Flatow E, Hoffman G, Lipska B, Lewis D, Haroutunian V, Hahn C, Charney A, Dracheva S, Kozlenkov A, Belmont J, DelValle D, Francoeur N, Hadjimichael E, Pinto D, van Bakel H, Roussos P, Fullard J, Bendl J, Hauberg M, Mangravite L, Peters M, Chae Y, Peng J, Niu M, Wang X, Webster M, Beach T, Chen C, Jiang Y, Dai R, Shieh A, Liu C, Grennan K, Xia Y, Vadukapuram R, Wang Y, Fitzgerald D, Cheng L, Brown M, Brown M, Brunetti T, Goodman T, Alsayed M, Gandal M, Geschwind D, Won H, Polioudakis D, Wamsley B, Yin J, Hadzic T, De La Torre Ubieta L, Swarup V, Sanders S, State M, Werling D, An J, Sheppard B, Willsey A, White K, Ray M, Giase G, Kefi A, Mattei E, Purcaro M, Weng Z, Moore J, Pratt H, Huey J, Borrman T, Sullivan P, Giusti-Rodriguez P, Kim Y, Sullivan P, Szatkiewicz J, Rhie S, Armoskus C, Camarena A, Farnham P, Spitsyna V, Witt H, Schreiner S, Evgrafov O, Knowles J, Gerstein M, Liu S, Wang D, Navarro F, Warrell J, Clarke D, Emani P, Gu M, Shi X, Xu M, Yang Y, Kitchen R, Gürsoy G, Zhang J, Carlyle B, Nairn A, Li M, Pochareddy S, Sestan N, Skarica M, Li Z, Sousa A, Santpere G, Choi J, Zhu Y, Gao T, Miller D, Cherskov A, Yang M, Amiri A, Coppola G, Mariani J, Scuderi S, Szekely A, Vaccarino F, Wu F, Weissman S, Roychowdhury T, Abyzov A. Comprehensive functional genomic resource and integrative model for the human brain. Science 2018, 362 PMID: 30545857, PMCID: PMC6413328, DOI: 10.1126/science.aat8464.Peer-Reviewed Original ResearchConceptsQuantitative trait lociCell type proportionsComprehensive functional genomics resourceExpression quantitative trait lociFunctional genomics resourcesSingle-cell expression profilesGene regulatory networksFurther quantitative trait lociPsychENCODE ConsortiumGenomic resourcesComprehensive online resourceRegulatory networksKey genesCross-population variationExpression profilesMolecular mechanismsCell typesGenesAdult brainPolygenic risk scoresStudy variantsChromatinSplicingGenetic riskInterpretable deep learning model