2024
Resolving 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-specific
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 Research
2019
Haplotype-resolved and integrated genome analysis of the cancer cell line HepG2
Zhou B, Ho S, Greer S, Spies N, Bell J, Zhang X, Zhu X, Arthur J, Byeon S, Pattni R, Saha I, Huang Y, Song G, Perrin D, Wong W, Ji H, Abyzov A, Urban A. Haplotype-resolved and integrated genome analysis of the cancer cell line HepG2. Nucleic Acids Research 2019, 47: 3846-3861. PMID: 30864654, PMCID: PMC6486628, DOI: 10.1093/nar/gkz169.Peer-Reviewed Original ResearchConceptsGenome sequenceStructural variantsGenomic structural featuresSomatic genomic rearrangementsFunctional genomics dataAllele-specific expressionEntire chromosome armsIntegrated genome analysisCRISPR/Cas9Cell linesMain cell linesGenome structureEpigenomic characteristicsChromosome armsGenome analysisDNA methylationGenome characteristicsRetrotransposon insertionChromosomal segmentsGenomic rearrangementsGenomic dataRegulatory complexityCell line HepG2Copy numberLoss of heterozygosityChromatin organization modulates the origin of heritable structural variations in human genome
Roychowdhury T, Abyzov A. Chromatin organization modulates the origin of heritable structural variations in human genome. Nucleic Acids Research 2019, 47: 2766-2777. PMID: 30773596, PMCID: PMC6451188, DOI: 10.1093/nar/gkz103.Peer-Reviewed Original ResearchComprehensive, integrated, and phased whole-genome analysis of the primary ENCODE cell line K562
Zhou B, Ho S, Greer S, Zhu X, Bell J, Arthur J, Spies N, Zhang X, Byeon S, Pattni R, Ben-Efraim N, Haney M, Haraksingh R, Song G, Ji H, Perrin D, Wong W, Abyzov A, Urban A. Comprehensive, integrated, and phased whole-genome analysis of the primary ENCODE cell line K562. Genome Research 2019, 29: 472-484. PMID: 30737237, PMCID: PMC6396411, DOI: 10.1101/gr.234948.118.Peer-Reviewed Original ResearchConceptsWhole-genome analysisStructural variantsFunctional genomicsEpigenomic dataAllele-specific DNA methylationComprehensive whole-genome analysisWhole-genome bisulfite sequencing dataGenomic structural featuresCopy numberLinked-read sequencingAllele-specific expressionEntire chromosome armsBisulfite sequencing dataAllele-specific deletionsComplex structural variantsTumor suppressor geneEpigenomic characteristicsChromosome armsGenome sequenceChromosome segmentsDNA methylationRNA-seqGenome characteristicsRetrotransposon insertionGenomic variant information
2017
Landscape and variation of novel retroduplications in 26 human populations
Zhang Y, Li S, Abyzov A, Gerstein MB. Landscape and variation of novel retroduplications in 26 human populations. PLOS Computational Biology 2017, 13: e1005567. PMID: 28662076, PMCID: PMC5510864, DOI: 10.1371/journal.pcbi.1005567.Peer-Reviewed Original ResearchConceptsParent genesSequencing dataHigh-coverage exomesLow-coverage whole-genome sequencing dataHuman populationWhole-genome sequencing dataExon-exon junctionsGenomes Phase 3Young L1 elementsPaired-end readsPotential disease associationsRetrotranspositional activityGenomic elementsNucleosome positioningPhylogenetic treeRetroduplicationExome sequencing dataReference genomeGenomic featuresInsertion eventsL1 elementsComprehensive discoveryPopulation markersSNP callingFunctional regionsIntersection 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 developmentComprehensive performance comparison of high-resolution array platforms for genome-wide Copy Number Variation (CNV) analysis in humans
Haraksingh RR, Abyzov A, Urban AE. Comprehensive performance comparison of high-resolution array platforms for genome-wide Copy Number Variation (CNV) analysis in humans. BMC Genomics 2017, 18: 321. PMID: 28438122, PMCID: PMC5402652, DOI: 10.1186/s12864-017-3658-x.Peer-Reviewed Original ResearchMeSH KeywordsCytogeneticsDNA Copy Number VariationsGenome, HumanGenomicsHumansOligonucleotide Array Sequence AnalysisConceptsCopy number variants
2016
Elevated variant density around SV breakpoints in germline lineage lends support to error-prone replication hypothesis
Dhokarh D, Abyzov A. Elevated variant density around SV breakpoints in germline lineage lends support to error-prone replication hypothesis. Genome Research 2016, 26: 874-881. PMID: 27216746, PMCID: PMC4937565, DOI: 10.1101/gr.205484.116.Peer-Reviewed Original ResearchConceptsSNPs/indelsComplex genomic rearrangementsHundreds of lociComplex human traitsAllele frequency spectrumReplication-based mechanismsBreakpoints of deletionsGermline lineageParental genomesSV breakpointsGenomic rearrangementsGenome ProjectMutational mechanismsDeletion eventsGenomic disordersHeterozygous SNPsStructural variantsVariant densityHuman traitsIndelsNumber variantsFold changeGermline deletionCNV formationDeletionA uniform survey of allele-specific binding and expression over 1000-Genomes-Project individuals
Chen J, Rozowsky J, Galeev TR, Harmanci A, Kitchen R, Bedford J, Abyzov A, Kong Y, Regan L, Gerstein M. A uniform survey of allele-specific binding and expression over 1000-Genomes-Project individuals. Nature Communications 2016, 7: 11101. PMID: 27089393, PMCID: PMC4837449, DOI: 10.1038/ncomms11101.Peer-Reviewed Original ResearchMeSH KeywordsAlgorithmsBinding SitesChromosome MappingComputational BiologyDatabases, GeneticGene ExpressionGene FrequencyGenome, HumanGenomicsGenotypeHigh-Throughput Nucleotide SequencingHuman Genome ProjectHumansInternetMolecular Sequence AnnotationPolymorphism, Single NucleotidePrecision MedicineConceptsSingle nucleotide variantsAllele-specific bindingFunctional genomics data setsAllele-specific behaviorLarge-scale sequencingGenomic data setsAllelic imbalanceNumber of readsChIP-seqRNA-seqGenome ProjectMaternal chromosomesNucleotide variantsPersonal genomesMapping biasAllelic variantsVariant catalogMultiple individualsFunctional effectsProject individualsBindingExpressionVariantsGenomeChromosomes
2015
Understanding genome structural variations
Abyzov A, Li S, Gerstein MB. Understanding genome structural variations. Oncotarget 2015, 7: 7370-7371. PMID: 26657727, PMCID: PMC4884923, DOI: 10.18632/oncotarget.6485.Peer-Reviewed Original ResearchAn integrated map of structural variation in 2,504 human genomes
Sudmant PH, Rausch T, Gardner EJ, Handsaker RE, Abyzov A, Huddleston J, Zhang Y, Ye K, Jun G, Hsi-Yang Fritz M, Konkel MK, Malhotra A, Stütz AM, Shi X, Paolo Casale F, Chen J, Hormozdiari F, Dayama G, Chen K, Malig M, Chaisson MJP, Walter K, Meiers S, Kashin S, Garrison E, Auton A, Lam HYK, Jasmine Mu X, Alkan C, Antaki D, Bae T, Cerveira E, Chines P, Chong Z, Clarke L, Dal E, Ding L, Emery S, Fan X, Gujral M, Kahveci F, Kidd JM, Kong Y, Lameijer EW, McCarthy S, Flicek P, Gibbs RA, Marth G, Mason CE, Menelaou A, Muzny DM, Nelson BJ, Noor A, Parrish NF, Pendleton M, Quitadamo A, Raeder B, Schadt EE, Romanovitch M, Schlattl A, Sebra R, Shabalin AA, Untergasser A, Walker JA, Wang M, Yu F, Zhang C, Zhang J, Zheng-Bradley X, Zhou W, Zichner T, Sebat J, Batzer MA, McCarroll SA, Mills R, Gerstein M, Bashir A, Stegle O, Devine S, Lee C, Eichler E, Korbel J. An integrated map of structural variation in 2,504 human genomes. Nature 2015, 526: 75-81. PMID: 26432246, PMCID: PMC4617611, DOI: 10.1038/nature15394.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceGenetic Predisposition to DiseaseGenetic VariationGenetics, MedicalGenetics, PopulationGenome, HumanGenome-Wide Association StudyGenomicsGenotypeHaplotypesHomozygoteHumansMolecular Sequence DataMutation RatePhysical Chromosome MappingPolymorphism, Single NucleotideQuantitative Trait LociSequence Analysis, DNASequence DeletionConceptsStructural variantsHuman genomeExpression quantitative trait lociGenome-wide association studiesIndividual mutational eventsQuantitative trait lociComplex structural variantsHomozygous gene knockoutsDNA sequencing dataLoci subjectTrait lociHuman genesGene knockoutIntegrated mapSequencing dataAssociation studiesMutational eventsHaplotype blocksVariant classesFunctional impactPopulation stratificationGenomeNumerous diseasesHuman populationStructural variationsAnalysis of deletion breakpoints from 1,092 humans reveals details of mutation mechanisms
Abyzov A, Li S, Kim DR, Mohiyuddin M, Stütz AM, Parrish NF, Mu XJ, Clark W, Chen K, Hurles M, Korbel JO, Lam HY, Lee C, Gerstein MB. Analysis of deletion breakpoints from 1,092 humans reveals details of mutation mechanisms. Nature Communications 2015, 6: 7256. PMID: 26028266, PMCID: PMC4451611, DOI: 10.1038/ncomms8256.Peer-Reviewed Original ResearchConceptsNon-allelic homologous recombinationTemplate-switching eventsGenomic structural variantsDeletion breakpointsHi-C interactionsNon-homologous mechanismsRelaxed selectionGenomic averageHistone marksOpen chromatinGenomic sitesGermline cellsDNA replicationCell divisionDNA methylationHomologous recombinationGenome ProjectStructural variantsBasepair resolutionNearby SNPsMutation mechanismMicroinsertionsBreakpointsChromatinIndels
2013
Integrative Annotation of Variants from 1092 Humans: Application to Cancer Genomics
Khurana E, Fu Y, Colonna V, Mu XJ, Kang HM, Lappalainen T, Sboner A, Lochovsky L, Chen J, Harmanci A, Das J, Abyzov A, Balasubramanian S, Beal K, Chakravarty D, Challis D, Chen Y, Clarke D, Clarke L, Cunningham F, Evani US, Flicek P, Fragoza R, Garrison E, Gibbs R, Gümüş ZH, Herrero J, Kitabayashi N, Kong Y, Lage K, Liluashvili V, Lipkin SM, MacArthur DG, Marth G, Muzny D, Pers TH, Ritchie GRS, Rosenfeld JA, Sisu C, Wei X, Wilson M, Xue Y, Yu F, Consortium 1, Dermitzakis ET, Yu H, Rubin MA, Tyler-Smith C, Gerstein M. Integrative Annotation of Variants from 1092 Humans: Application to Cancer Genomics. Science 2013, 342: 1235587. PMID: 24092746, PMCID: PMC3947637, DOI: 10.1126/science.1235587.Peer-Reviewed Original ResearchAnalysis of variable retroduplications in human populations suggests coupling of retrotransposition to cell division
Abyzov A, Iskow R, Gokcumen O, Radke DW, Balasubramanian S, Pei B, Habegger L, Consortium T, Lee C, Gerstein M. Analysis of variable retroduplications in human populations suggests coupling of retrotransposition to cell division. Genome Research 2013, 23: 2042-2052. PMID: 24026178, PMCID: PMC3847774, DOI: 10.1101/gr.154625.113.Peer-Reviewed Original ResearchConceptsCell divisionCorrect phylogenetic treeGenomes Project ConsortiumHuman populationTranscription of mRNARetroduplicationPhylogenetic treeParent genesGenomic integrationCell cycleG1 transitionMore copiesGenesRetrotranspositionHuman subpopulationsMultiple linesRetrogenesPseudogenesTranscriptionDivisionRNAVariantsProteinMRNACopiesChild Development and Structural Variation in the Human Genome
Zhang Y, Haraksingh R, Grubert F, Abyzov A, Gerstein M, Weissman S, Urban AE. Child Development and Structural Variation in the Human Genome. Child Development 2013, 84: 34-48. PMID: 23311762, DOI: 10.1111/cdev.12051.Peer-Reviewed Original Research
2012
Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells
Abyzov A, Mariani J, Palejev D, Zhang Y, Haney MS, Tomasini L, Ferrandino AF, Rosenberg Belmaker LA, Szekely A, Wilson M, Kocabas A, Calixto NE, Grigorenko EL, Huttner A, Chawarska K, Weissman S, Urban AE, Gerstein M, Vaccarino FM. Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells. Nature 2012, 492: 438-442. PMID: 23160490, PMCID: PMC3532053, DOI: 10.1038/nature11629.Peer-Reviewed Original ResearchArchitecture of the human regulatory network derived from ENCODE data
Gerstein MB, Kundaje A, Hariharan M, Landt SG, Yan KK, Cheng C, Mu XJ, Khurana E, Rozowsky J, Alexander R, Min R, Alves P, Abyzov A, Addleman N, Bhardwaj N, Boyle AP, Cayting P, Charos A, Chen DZ, Cheng Y, Clarke D, Eastman C, Euskirchen G, Frietze S, Fu Y, Gertz J, Grubert F, Harmanci A, Jain P, Kasowski M, Lacroute P, Leng J, Lian J, Monahan H, O’Geen H, Ouyang Z, Partridge EC, Patacsil D, Pauli F, Raha D, Ramirez L, Reddy TE, Reed B, Shi M, Slifer T, Wang J, Wu L, Yang X, Yip KY, Zilberman-Schapira G, Batzoglou S, Sidow A, Farnham PJ, Myers RM, Weissman SM, Snyder M. Architecture of the human regulatory network derived from ENCODE data. Nature 2012, 489: 91-100. PMID: 22955619, PMCID: PMC4154057, DOI: 10.1038/nature11245.Peer-Reviewed Original ResearchMeSH KeywordsAllelesCell LineDNAEncyclopedias as TopicGATA1 Transcription FactorGene Expression ProfilingGene Regulatory NetworksGenome, HumanGenomicsHumansK562 CellsMolecular Sequence AnnotationOrgan SpecificityPhosphorylationPolymorphism, Single NucleotideProtein Interaction MapsRegulatory Sequences, Nucleic AcidRNA, UntranslatedSelection, GeneticTranscription FactorsTranscription Initiation SiteConceptsTranscription factorsRegulatory networksHuman transcriptional regulatory networkHuman regulatory networkSpecific genomic locationsTranscription-related factorsState of genesTranscriptional regulatory networksAllele-specific activityPersonal genome sequencesGenomic locationStrong selectionGenome sequenceENCODE dataGenomic informationInformation-flow bottlenecksRegulatory informationConnected network componentsCombinatorial fashionInfluences expressionHuman biologyBinding informationNetwork motifsCo-associationGenes
2011
Genome-Wide Mapping of Copy Number Variation in Humans: Comparative Analysis of High Resolution Array Platforms
Haraksingh RR, Abyzov A, Gerstein M, Urban AE, Snyder M. Genome-Wide Mapping of Copy Number Variation in Humans: Comparative Analysis of High Resolution Array Platforms. PLOS ONE 2011, 6: e27859. PMID: 22140474, PMCID: PMC3227574, DOI: 10.1371/journal.pone.0027859.Peer-Reviewed Original ResearchConceptsArray comparative genome hybridizationCopy number variantsHigh‐resolution array platformGenome-wide CNV detectionCNV detectionGenome-wide detectionHuman genomic variationComparative genome hybridizationSingle nucleotide polymorphism (SNP) genotypingCopy number variationsAffymetrix SNP 6.0 arraysArray-based platformsNucleotide polymorphism genotypingM-CGHWide mappingGenomic variationSNP 6.0 arraysCytogenetic researchWhole genomeGenome hybridizationSample NA12878Breakpoint resolutionNumber variationsNumber variantsGenomeCNVnator: An approach to discover, genotype, and characterize typical and atypical CNVs from family and population genome sequencing
Abyzov A, Urban AE, Snyder M, Gerstein M. CNVnator: An approach to discover, genotype, and characterize typical and atypical CNVs from family and population genome sequencing. Genome Research 2011, 21: 974-984. PMID: 21324876, PMCID: PMC3106330, DOI: 10.1101/gr.114876.110.Peer-Reviewed Original Research