2024
Transgenerational transmission of post-zygotic mutations suggests symmetric contribution of first two blastomeres to human germline
Jang Y, Tomasini L, Bae T, Szekely A, Vaccarino F, Abyzov A. Transgenerational transmission of post-zygotic mutations suggests symmetric contribution of first two blastomeres to human germline. Nature Communications 2024, 15: 9117. PMID: 39438473, PMCID: PMC11496613, DOI: 10.1038/s41467-024-53485-x.Peer-Reviewed Original ResearchSomatic 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 brainVariants
2023
Efficient reconstruction of cell lineage trees for cell ancestry and cancer
Jang Y, Fasching L, Bae T, Tomasini L, Schreiner J, Szekely A, Fernandez T, Leckman J, Vaccarino F, Abyzov A. Efficient reconstruction of cell lineage trees for cell ancestry and cancer. Nucleic Acids Research 2023, 51: e57-e57. PMID: 37026484, PMCID: PMC10250207, DOI: 10.1093/nar/gkad254.Peer-Reviewed Original ResearchConceptsLineage treesCell ancestryCell lineage treesFirst cell divisionStem cell linesPluripotent stem cell lineLineage reconstructionInduced pluripotent stem cell lineCell divisionCancer progressionLineage representationCell linesMosaic mutationsHuman skin fibroblastsTreesMutationsAncestrySkin fibroblastsMultiple cellsGenomeLineagesZygotesLinesFibroblastsCellsClonally Selected Lines After CRISPR-Cas Editing Are Not Isogenic
Panda A, Suvakov M, Mariani J, Drucker K, Park Y, Jang Y, Kollmeyer T, Sarkar G, Bae T, Kim J, Yoon W, Jenkins R, Vaccarino F, Abyzov A. Clonally Selected Lines After CRISPR-Cas Editing Are Not Isogenic. The CRISPR Journal 2023, 6: 176-182. PMID: 37071670, PMCID: PMC10123805, DOI: 10.1089/crispr.2022.0050.Peer-Reviewed Original ResearchConceptsCopy number alterationsSeparate genomic lociSingle nucleotide mutationsApplication of CRISPRCRISPR-Cas editingOff-target editsScreening of clonesGenomic divergenceWhole-genome sequencingGenomic lociSelection of clonesGenome sequencingNucleotide mutationsTarget editsCultured cellsClonal linesNumber alterationsCell cloningClonesMutationsCloningCRISPRComprehensive 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
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 ResearchConceptsTranscription factorsSomatic mutationsPutative transcription factorEnhancer-like regionSingle nucleotide mutationsWhole-genome sequencingGene regulationSomatic duplicationGenome sequencingDamaging mutationsBackground mutagenesisMutationsHypermutabilityClonal expansionMotifDiseased brainPotential linkVivo clonal expansionMutagenesisGenesDuplicationSequencingRegulation
2020
SCELLECTOR: ranking amplification bias in single cells using shallow sequencing
Sarangi V, Jourdon A, Bae T, Panda A, Vaccarino F, Abyzov A. SCELLECTOR: ranking amplification bias in single cells using shallow sequencing. BMC Bioinformatics 2020, 21: 521. PMID: 33183232, PMCID: PMC7663899, DOI: 10.1186/s12859-020-03858-y.Peer-Reviewed Original ResearchConceptsMultiple displacement amplificationShallow sequencingSingle-cell platformsSingle-cell sequencingCoverage sequencing dataSingle cellsHuman neuronal cellsMosaic mutationsAmount of DNAAmplification qualityCell sequencingCoverage sequencingHigh-coverage dataSequencing dataHaplotype informationPhi29 polymeraseDNA damageIndividual cellsNeuronal cellsSequencingAmplification biasAllelic imbalancePresence of sitesMutationsFragment lengthAdult diffuse glioma GWAS by molecular subtype identifies variants in D2HGDH and FAM20C
Eckel-Passow J, Drucker K, Kollmeyer T, Kosel M, Decker P, Molinaro A, Rice T, Praska C, Clark L, Caron A, Abyzov A, Batzler A, Song J, Pekmezci M, Hansen H, McCoy L, Bracci P, Wiemels J, Wiencke J, Francis S, Burns T, Giannini C, Lachance D, Wrensch M, Jenkins R. Adult diffuse glioma GWAS by molecular subtype identifies variants in D2HGDH and FAM20C. Neuro-Oncology 2020, 22: 1602-1613. PMID: 32386320, PMCID: PMC7690366, DOI: 10.1093/neuonc/noaa117.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesGenome-wide p-value thresholdGlioma genome-wide association studiesElongation helicase 1Germline variantsChromosome 2Helicase 1Identifies variantsChromosome 7Association studiesChromosome 20Molecular subtypesMutationsGlioma molecular subtypesWild-type gliomasFAM20CDehydrogenase mutationsP-value thresholdPromoter mutationsAssociation of variantsIsocitrate dehydrogenase (IDH) mutationD2HGDHTelomerase reverse transcriptase (TERT) promoter mutationsNew regionsVariants
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 development