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 brainVariants
2023
Clonally 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 cloningClonesMutationsCloningCRISPR
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
2021
Landmarks of human embryonic development inscribed in somatic mutations
Bizzotto S, Dou Y, Ganz J, Doan R, Kwon M, Bohrson C, Kim S, Bae T, Abyzov A, Network† N, Park P, Walsh C. Landmarks of human embryonic development inscribed in somatic mutations. Science 2021, 371: 1249-1253. PMID: 33737485, PMCID: PMC8170505, DOI: 10.1126/science.abe1544.Peer-Reviewed Original ResearchConceptsSomatic single nucleotide variantsHuman embryonic developmentEmbryonic developmentEarly embryonic cell divisionsTransposase-accessible chromatin sequencingSingle cellsSingle-nucleus assayHigh-depth whole-genome sequencingSingle-nucleus RNA sequencingEmbryonic cell divisionCell lineage informationDistinct germ layersOnset of gastrulationSingle nucleotide variantsOrganismal developmentWhole-genome sequencingExtraembryonic tissuesCell divisionRNA sequencingProgenitor poolLineage informationGerm layersEarly progenitorsMultiple tissuesSequencing
2018
Molecular characterization of colorectal adenomas with and without malignancy reveals distinguishing genome, transcriptome and methylome alterations
Druliner B, Wang P, Bae T, Baheti S, Slettedahl S, Mahoney D, Vasmatzis N, Xu H, Kim M, Bockol M, O’Brien D, Grill D, Warner N, Munoz-Gomez M, Kossick K, Johnson R, Mouchli M, Felmlee-Devine D, Washechek-Aletto J, Smyrk T, Oberg A, Wang J, Chia N, Abyzov A, Ahlquist D, Boardman L. Molecular characterization of colorectal adenomas with and without malignancy reveals distinguishing genome, transcriptome and methylome alterations. Scientific Reports 2018, 8: 3161. PMID: 29453410, PMCID: PMC5816667, DOI: 10.1038/s41598-018-21525-4.Peer-Reviewed Original ResearchConceptsColorectal cancerManagement of polypsPolyp patientsPolyp groupMalignant polypsPrecursor lesionsColorectal adenomasResidual polypPolyp tissuesPolyp sizePolypsCancerAltered expressionMethylome alterationsPatientsWhole-genome sequencingTissueMore mutationsAlterationsExpression changesSignificant expression changesMolecular determinantsMethylation alterationsMolecular distinctionMolecular characterization
2016
Colorectal Cancer with Residual Polyp of Origin: A Model of Malignant Transformation
Druliner B, Rashtak S, Ruan X, Bae T, Vasmatzis N, O’Brien D, Johnson R, Felmlee-Devine D, Washechek-Aletto J, Basu N, Liu H, Smyrk T, Abyzov A, Boardman L. Colorectal Cancer with Residual Polyp of Origin: A Model of Malignant Transformation. Translational Oncology 2016, 9: 280-286. PMID: 27567950, PMCID: PMC4941582, DOI: 10.1016/j.tranon.2016.06.002.Peer-Reviewed Original ResearchColorectal cancerResidual polypBiopsy-proven colorectal cancerEquivalent hazard ratiosEarly-stage diseaseSame disease stageRemnant polypsHazard ratioOverall survivalCancer Genome AtlasClinical coursePathologic characteristicsDisease stageMayo ClinicAdenomatous polypsColorectal carcinogenesisMalignant transformationCarcinoma transitionPolypsGenome AtlasGene expression profilesGenomic profilesWhole-genome sequencingCancerAge