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 brainVariantsResolving the 22q11.2 deletion using CTLR-Seq reveals chromosomal rearrangement mechanisms and individual variance in breakpoints
Zhou B, Purmann C, Guo H, Shin G, Huang Y, Pattni R, Meng Q, Greer S, Roychowdhury T, Wood R, Ho M, Dohna H, Abyzov A, Hallmayer J, Wong W, Ji H, Urban A. Resolving the 22q11.2 deletion using CTLR-Seq reveals chromosomal rearrangement mechanisms and individual variance in breakpoints. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2322834121. PMID: 39042694, PMCID: PMC11295037, DOI: 10.1073/pnas.2322834121.Peer-Reviewed Original ResearchConceptsLong-read sequencingPulse-field gel electrophoresisBase-pair resolutionDNA methylation patternsCell-type specific analysisCell type-specificChromosomal interactionsSequence assemblySegmental duplicationsGenome sequenceGenomic rearrangementsGenomic regionsChromosomal breakpointsHuman genomeGenomic recombinationMethylation patternsSequence analysisHaplotype-specificDeletion haplotypesGel electrophoresisGenomeAmplification-freeBreakpoint locationsMicrodeletion disorderType-specificGenome-wide analysis and visualization of copy number with CNVpytor in igv.js
Panda A, Suvakov M, Thorvaldsdottir H, Mesirov J, Robinson J, Abyzov A. Genome-wide analysis and visualization of copy number with CNVpytor in igv.js. Bioinformatics 2024, 40: btae453. PMID: 39018173, PMCID: PMC11303504, DOI: 10.1093/bioinformatics/btae453.Peer-Reviewed Original ResearchA data-driven single-cell and spatial transcriptomic map of the human prefrontal cortex
Huuki-Myers L, Spangler A, Eagles N, Montgomery K, Kwon S, Guo B, Grant-Peters M, Divecha H, Tippani M, Sriworarat C, Nguyen A, Ravichandran P, Tran M, Seyedian A, Hyde T, Kleinman J, Battle A, Page S, Ryten M, Hicks S, Martinowich K, Collado-Torres L, Maynard 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, 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. A data-driven single-cell and spatial transcriptomic map of the human prefrontal cortex. Science 2024, 384: eadh1938. PMID: 38781370, PMCID: PMC11398705, DOI: 10.1126/science.adh1938.Peer-Reviewed Original ResearchConceptsRNA sequencing dataCell type compositionGene expression platformSpatial transcriptomics technologiesAnterior-posterior axisCell-cell interactionsTranscriptome mapExpression platformHuman dorsolateral prefrontal cortexTranscriptomic technologiesSingle-cellCell typesPrefrontal cortexMolecular organizationDorsolateral prefrontal cortexHuman prefrontal cortexSingle-cell multi-cohort dissection of the schizophrenia transcriptome
Ruzicka W, Mohammadi S, Fullard J, Davila-Velderrain J, Subburaju S, Tso D, Hourihan M, Jiang S, Lee H, Bendl J, Voloudakis G, Haroutunian V, Hoffman G, Roussos P, Kellis M, Akbarian S, Abyzov A, Ahituv N, Arasappan D, Almagro Armenteros J, Beliveau B, 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, Deep-Soboslay A, Deng C, DiPietro C, Dracheva S, Drusinsky S, Duan Z, Duong D, Dursun C, Eagles N, Edelstein J, Emani P, 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, Hawken N, He C, Henry E, Hicks S, Ho M, Ho L, 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, 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, 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, Rozowsky J, Ruth M, 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, Sudhof T, Snyder M, Tao R, Therrien K, Tsai L, Urban A, Vaccarino F, van Bakel H, Vo D, 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. Single-cell multi-cohort dissection of the schizophrenia transcriptome. Science 2024, 384: eadg5136. PMID: 38781388, DOI: 10.1126/science.adg5136.Peer-Reviewed Original ResearchConceptsGenetic risk factorsRisk factorsTranscriptional changesHeterogeneity of schizophreniaNeuronal cell statesSchizophrenia pathophysiologySingle-cell dissectionExcitatory neuronsEffective therapySchizophrenia transcriptomicsCortical cytoarchitectureSingle-cell atlasGenomic variantsCell groupsHuman prefrontal cortexMolecular pathwaysSchizophreniaTranscriptional alterationsTranscriptomic changesPrefrontal cortexCell statesAlterationsTherapyPathophysiologyDissectionSingle-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 tissuesExpressionCellsChromatinLociMultiomicsMassively 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 ResearchConceptsGene 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 cortexNucleotideCross-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 maturationRegulationCharacterization 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
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 ResearchModeling idiopathic autism in forebrain organoids reveals an imbalance of excitatory cortical neuron subtypes during early neurogenesis
Jourdon A, Wu F, Mariani J, Capauto D, Norton S, Tomasini L, Amiri A, Suvakov M, Schreiner J, Jang Y, Panda A, Nguyen C, Cummings E, Han G, Powell K, Szekely A, McPartland J, Pelphrey K, Chawarska K, Ventola P, Abyzov A, Vaccarino F. Modeling idiopathic autism in forebrain organoids reveals an imbalance of excitatory cortical neuron subtypes during early neurogenesis. Nature Neuroscience 2023, 26: 1505-1515. PMID: 37563294, PMCID: PMC10573709, DOI: 10.1038/s41593-023-01399-0.Peer-Reviewed Original ResearchConceptsIdiopathic autism spectrum disorderCortical neuron subtypesAutism spectrum disorderEarly cortical developmentCortical organoidsCortical plateExcitatory neuronsCortical developmentRare formNeuron subtypesUnaffected fatherASD pathogenesisForebrain organoidsEarly neurogenesisRare variantsIdiopathic autismRisk genesTranscriptomic alterationsNeuronsProbandsSingle-cell transcriptomicsForebrain developmentSpectrum disorderTranscriptomic changesAlterationsEfficient 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 resectionProfilingControl-independent mosaic single nucleotide variant detection with DeepMosaic
Yang X, Xu X, Breuss M, Antaki D, Ball L, Chung C, Shen J, Li C, George R, Wang Y, Bae T, Cheng Y, Abyzov A, Wei L, Alexandrov L, Sebat J, Gleeson J. Control-independent mosaic single nucleotide variant detection with DeepMosaic. Nature Biotechnology 2023, 41: 870-877. PMID: 36593400, PMCID: PMC10314968, DOI: 10.1038/s41587-022-01559-w.Peer-Reviewed Original Research
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 StatementsA noncoding single-nucleotide polymorphism at 8q24 drives IDH1-mutant glioma formation
Yanchus C, Drucker K, Kollmeyer T, Tsai R, Winick-Ng W, Liang M, Malik A, Pawling J, De Lorenzo S, Ali A, Decker P, Kosel M, Panda A, Al-Zahrani K, Jiang L, Browning J, Lowden C, Geuenich M, Hernandez J, Gosio J, Ahmed M, Loganathan S, Berman J, Trcka D, Michealraj K, Fortin J, Carson B, Hollingsworth E, Jacinto S, Mazrooei P, Zhou L, Elia A, Lupien M, He H, Murphy D, Wang L, Abyzov A, Dennis J, Maass P, Campbell K, Wilson M, Lachance D, Wrensch M, Wiencke J, Mak T, Pennacchio L, Dickel D, Visel A, Wrana J, Taylor M, Zadeh G, Dirks P, Eckel-Passow J, Attisano L, Pombo A, Ida C, Kvon E, Jenkins R, Schramek D. A noncoding single-nucleotide polymorphism at 8q24 drives IDH1-mutant glioma formation. Science 2022, 378: 68-78. PMID: 36201590, PMCID: PMC9926876, DOI: 10.1126/science.abj2890.Peer-Reviewed Original ResearchConceptsNoncoding single nucleotide polymorphismSingle nucleotide polymorphismsCausal variantsMolecular pathwaysIsocitrate dehydrogenaseLethal gliomaHeritable predispositionGlioma formationTumor developmentLow-grade gliomasMutant lower grade gliomasPolymorphismMouse modelPromoterLociEnhancerSixfold greater riskRs55705857PathwayMechanisticallyDehydrogenaseDisruptsExpressionPenetranceCancer riskAnalysis 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 expansionMutagenesisGenesDuplicationSequencingRegulationPostmortem Human Dura Mater Cells Exhibit Phenotypic, Transcriptomic and Genetic Abnormalities that Impact their Use for Disease Modeling
Argouarch A, Schultz N, Yang A, Jang Y, Garcia K, Cosme C, Corrales C, Nana A, Karydas A, Spina S, Grinberg L, Miller B, Wyss-Coray T, Abyzov A, Goodarzi H, Seeley W, Kao A. Postmortem Human Dura Mater Cells Exhibit Phenotypic, Transcriptomic and Genetic Abnormalities that Impact their Use for Disease Modeling. Stem Cell Reviews And Reports 2022, 18: 3050-3065. PMID: 35809166, PMCID: PMC9622518, DOI: 10.1007/s12015-022-10416-x.Peer-Reviewed Original ResearchConceptsDivergent gene expression profilesDefective DNA damage repairDisease modelingDNA damage repairGene expression profilesSpecific cell typesCell linesDura mater cellsDermal fibroblastsSomatic mutation signaturesPatient-derived cellsNormal biologyDamage repairExpression profilesSlow growth rateDifferentiation protocolsCell typesFibroblast-like cellsMutation signaturesProtein markersHuman dermal fibroblastsExhibit phenotypicNeurodegenerative diseasesDura materFibroblasts