2024
Cross-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 maturationRegulationUsing a comprehensive atlas and predictive models to reveal the complexity and evolution of brain-active regulatory elements
Pratt H, Andrews G, Shedd N, Phalke N, Li T, Pampari A, Jensen M, Wen C, Consortium P, Gandal M, Geschwind D, Gerstein M, Moore J, Kundaje A, Colubri A, Weng Z. Using a comprehensive atlas and predictive models to reveal the complexity and evolution of brain-active regulatory elements. Science Advances 2024, 10: eadj4452. PMID: 38781344, PMCID: PMC11114231, DOI: 10.1126/sciadv.adj4452.Peer-Reviewed Original ResearchConceptsEpigenetic dataCell-type-specific gene regulationCis-regulatory elementsComprehensive atlasGenetic variants associated with psychiatric disordersLineage-specific transcription factorsBrain cell typesMammalian elementsPsychENCODE ConsortiumNoncoding regionsEvolutionary historyGene regulationRegulatory elementsSequence mutationsTranscription factorsSequence syntaxRegulatory informationPrimate-specific sequencesBinding sitesHuman traitsCell typesFunctional implicationsPsychiatric disordersSequenceFetal brain development
2023
Beyond genome-wide association studies: Investigating the role of noncoding regulatory elements in primary sclerosing cholangitis
Pratt H, Wu T, Elhajjajy S, Zhou J, Fitzgerald K, Fazzio T, Weng Z, Pratt D. Beyond genome-wide association studies: Investigating the role of noncoding regulatory elements in primary sclerosing cholangitis. Hepatology Communications 2023, 7: e0242. PMID: 37756045, PMCID: PMC10531193, DOI: 10.1097/hc9.0000000000000242.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesRegulatory element activityRegulatory elementsElement activityAssociation studiesCell type-specific regulatory elementsPrimary sclerosing cholangitisNoncoding regions of DNANoncoding risk variantsRegulatory element functionNoncoding regulatory elementsPrimary sclerosing cholangitis patientsRegions of DNANoncoding variantsATAC-seqRisk lociEpigenomic datasetsNoncoding regionsRNA-seqEpigenomic studiesRisk variantsSclerosing cholangitisT cellsT cell responses to antigen stimulationPeripheral CD4+ T cellsThe EN-TEx resource of multi-tissue personal epigenomes & variant-impact models
Rozowsky J, Gao J, Borsari B, Yang Y, Galeev T, Gürsoy G, Epstein C, Xiong K, Xu J, Li T, Liu J, Yu K, Berthel A, Chen Z, Navarro F, Sun M, Wright J, Chang J, Cameron C, Shoresh N, Gaskell E, Drenkow J, Adrian J, Aganezov S, Aguet F, Balderrama-Gutierrez G, Banskota S, Corona G, Chee S, Chhetri S, Cortez Martins G, Danyko C, Davis C, Farid D, Farrell N, Gabdank I, Gofin Y, Gorkin D, Gu M, Hecht V, Hitz B, Issner R, Jiang Y, Kirsche M, Kong X, Lam B, Li S, Li B, Li X, Lin K, Luo R, Mackiewicz M, Meng R, Moore J, Mudge J, Nelson N, Nusbaum C, Popov I, Pratt H, Qiu Y, Ramakrishnan S, Raymond J, Salichos L, Scavelli A, Schreiber J, Sedlazeck F, See L, Sherman R, Shi X, Shi M, Sloan C, Strattan J, Tan Z, Tanaka F, Vlasova A, Wang J, Werner J, Williams B, Xu M, Yan C, Yu L, Zaleski C, Zhang J, Ardlie K, Cherry J, Mendenhall E, Noble W, Weng Z, Levine M, Dobin A, Wold B, Mortazavi A, Ren B, Gillis J, Myers R, Snyder M, Choudhary J, Milosavljevic A, Schatz M, Bernstein B, Guigó R, Gingeras T, Gerstein M. The EN-TEx resource of multi-tissue personal epigenomes & variant-impact models. Cell 2023, 186: 1493-1511.e40. PMID: 37001506, PMCID: PMC10074325, DOI: 10.1016/j.cell.2023.02.018.Peer-Reviewed Original Research
2022
Building integrative functional maps of gene regulation
Xu J, Pratt HE, Moore JE, Gerstein MB, Weng Z. Building integrative functional maps of gene regulation. Human Molecular Genetics 2022, 31: r114-r122. PMID: 36083269, PMCID: PMC9585680, DOI: 10.1093/hmg/ddac195.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsGene regulationRegulatory mapSame genetic informationNon-coding genesSuch regulatory elementsEvolutionary analysisHuman genomeRegulatory elementsGenetic informationGene expressionType diversityRegulatory roleGenomeBase pairsIndividual cellsFunctional assaysSpecific functionsRegulationCellsFunctional mapsGenesDNADiversityCopiesSequenceMafB, WDR77, and ß-catenin interact with each other and have similar genome association profiles
He L, Gao M, Pratt H, Weng Z, Struhl K. MafB, WDR77, and ß-catenin interact with each other and have similar genome association profiles. PLOS ONE 2022, 17: e0264799. PMID: 35482762, PMCID: PMC9049301, DOI: 10.1371/journal.pone.0264799.Peer-Reviewed Original ResearchAuthor Correction: Expanded encyclopaedias of DNA elements in the human and mouse genomes
Moore J, Purcaro M, Pratt H, Epstein C, Shoresh N, Adrian J, Kawli T, Davis C, Dobin A, Kaul R, Halow J, Van Nostrand E, Freese P, Gorkin D, Shen Y, He Y, Mackiewicz M, Pauli-Behn F, Williams B, Mortazavi A, Keller C, Zhang X, Elhajjajy S, Huey J, Dickel D, Snetkova V, Wei X, Wang X, Rivera-Mulia J, Rozowsky J, Zhang J, Chhetri S, Zhang J, Victorsen A, White K, Visel A, Yeo G, Burge C, Lécuyer E, Gilbert D, Dekker J, Rinn J, Mendenhall E, Ecker J, Kellis M, Klein R, Noble W, Kundaje A, Guigó R, Farnham P, Cherry J, Myers R, Ren B, Graveley B, Gerstein M, Pennacchio L, Snyder M, Bernstein B, Wold B, Hardison R, Gingeras T, Stamatoyannopoulos J, Weng Z. Author Correction: Expanded encyclopaedias of DNA elements in the human and mouse genomes. Nature 2022, 605: e3-e3. PMID: 35474001, PMCID: PMC9095460, DOI: 10.1038/s41586-021-04226-3.Peer-Reviewed Original Research
2021
Integration of high-resolution promoter profiling assays reveals novel, cell type-specific transcription start sites across 115 human cell and tissue types
Moore J, Zhang X, Elhajjajy S, Fan K, Pratt H, Reese F, Mortazavi A, Weng Z. Integration of high-resolution promoter profiling assays reveals novel, cell type-specific transcription start sites across 115 human cell and tissue types. Genome Research 2021, 32: gr.275723.121. PMID: 34949670, PMCID: PMC8805725, DOI: 10.1101/gr.275723.121.Peer-Reviewed Original ResearchConceptsTranscription start site annotationTranscription start siteGenome-wide association studiesStart siteAccurate transcription start siteCell type-specific usageMapping of promotersPaired-end informationPaired-end readsAnalysis of gene expressionTranscriptomic data setsGENCODE genesRNA annotationGWAS genesPaired-endGenomic positionsGene collectionTissue typesAssociation studiesTranscriptional regulationTranscription assaysBiological communitiesGene expressionHuman diseasesHuman cellsFactorbook: an updated catalog of transcription factor motifs and candidate regulatory motif sites
Pratt H, Andrews G, Phalke N, Huey J, Purcaro M, van der Velde A, Moore J, Weng Z. Factorbook: an updated catalog of transcription factor motifs and candidate regulatory motif sites. Nucleic Acids Research 2021, 50: d141-d149. PMID: 34755879, PMCID: PMC8728199, DOI: 10.1093/nar/gkab1039.Peer-Reviewed Original ResearchConceptsChIP-seqHT-SELEXTranscription factorsDNA-binding transcription factorsHT-SELEX experimentsChIP-seq dataChIP-seq experimentsAnnotation of variantsTF binding sitesCis-regulatory elementsTranscriptional regulatory proteinsDatabase of annotationsIntegrated analysisENCODE projectHuman genomeMotif modelsTrait heritabilityRegulatory proteinsBinding specificityGene expressionMotifBinding sitesCell typesRegulatory effectsComprehensive collectionYAP and TAZ are transcriptional co-activators of AP-1 proteins and STAT3 during breast cellular transformation
He L, Pratt H, Gao M, Wei F, Weng Z, Struhl K. YAP and TAZ are transcriptional co-activators of AP-1 proteins and STAT3 during breast cellular transformation. ELife 2021, 10: e67312. PMID: 34463254, PMCID: PMC8463077, DOI: 10.7554/elife.67312.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingCell Line, TumorCell Transformation, NeoplasticDatabases, GeneticFemaleGene Expression Regulation, NeoplasticHumansIntracellular Signaling Peptides and ProteinsProtein BindingProtein Interaction Domains and MotifsSignal TransductionSTAT3 Transcription FactorTranscription Factor AP-1Transcription FactorsTranscriptional ActivationTranscriptional Coactivator with PDZ-Binding Motif ProteinsTriple Negative Breast NeoplasmsYAP-Signaling ProteinsConceptsTranscriptional co-activatorAP-1 proteinsAP-1Cellular transformationTarget siteNon-overlapping genesStimulated transcriptional activityAssociated with poor survival of breast cancer patientsPoor survival of breast cancer patientsSTAT3 motifTEAD proteinsSequence motifsGene classesWW domainEpigenetic switchTaz paralogTAZ-specificTranscriptional activityTranscription factorsTEADYAP/TAZSTAT3MotifTAZJunBInvestigating the Potential Roles of SINEs in the Human Genome
Zhang X, Pratt H, Weng Z. Investigating the Potential Roles of SINEs in the Human Genome. Annual Review Of Genomics And Human Genetics 2021, 22: 1-20. PMID: 33792357, DOI: 10.1146/annurev-genom-111620-100736.Peer-Reviewed Original ResearchConceptsShort interspersed nuclear elementsHuman genomePol II-transcribed genesFunctional regulatory elementsGene-rich regionsRNA polymerase IIIProximity to genesInterspersed nuclear elementsRegulate gene expressionPotential regulatory functionsSINE RNAsNonautonomous retrotransposonsPolymerase IIIGene regulationRegulatory elementsAutonomous retroelementsGenomeNuclear elementsGene expressionGenesRNARNA levelsPolPotential roleRetrotransposonsGenome-wide detection and analysis of CRISPR-Cas off-targets
Rodríguez T, Dadafarin S, Pratt H, Liu P, Amrani N, Zhu L. Genome-wide detection and analysis of CRISPR-Cas off-targets. Progress In Nucleic Acid Research And Molecular Biology 2021, 181: 31-43. PMID: 34127199, DOI: 10.1016/bs.pmbts.2021.01.012.Peer-Reviewed Original ResearchConceptsProtospacer-adjacent motifOff-target identificationGUIDE-seqGenome-wide detectionHigh-throughput sequencingShort Palindromic Repeats (CRISPR) technologyOff-target sitesSequencing platformsThroughput sequencingTreat human diseasesOpen-source pipelineDocker imageHuman diseasesGene editingOff-targetsBiological studiesIncreased multiplexingProfiling approachSequenceIn vivoBioconductorSgRNAMotifRNAIdentificationYAP1 Withdrawal in Hepatoblastoma Drives Therapeutic Differentiation of Tumor Cells to Functional Hepatocyte‐Like Cells
Smith J, Rodríguez T, Mou H, Kwan S, Pratt H, Zhang X, Cao Y, Liang S, Ozata D, Yu T, Yin Q, Hazeltine M, Weng Z, Sontheimer E, Xue W. YAP1 Withdrawal in Hepatoblastoma Drives Therapeutic Differentiation of Tumor Cells to Functional Hepatocyte‐Like Cells. Hepatology 2021, 73: 1011-1027. PMID: 32452550, PMCID: PMC8500588, DOI: 10.1002/hep.31389.Peer-Reviewed Original ResearchConceptsYes-associated protein 1Tumor cellsTumor regressionB-cateninStage IV hepatoblastomaResidual tumor cellsPediatric liver tumorsTherapeutic targetLong-term regressionTherapeutic differentiationHepatocyte-like morphologyFunctional hepatocyte-like cellsChildren's HbHB tumorsHepatocyte gene expressionHepatocyte-like cellsTranscription factor occupancyChemotherapeutic advancesTargeted therapyTumor landscapeLiver tumorsMurine modelHepatoblastomaTumorPromote cell deathAnnotation of chromatin states in 66 complete mouse epigenomes during development
van der Velde A, Fan K, Tsuji J, Moore J, Purcaro M, Pratt H, Weng Z. Annotation of chromatin states in 66 complete mouse epigenomes during development. Communications Biology 2021, 4: 239. PMID: 33619351, PMCID: PMC7900196, DOI: 10.1038/s42003-021-01756-4.Peer-Reviewed Original ResearchConceptsChromatin stateMouse epigenomesPolycomb repressive complex proteinsBivalent chromatin stateTranscription start siteRepressive mark H3K27me3Silence target genesCharacteristics of promotersChromHMM algorithmUnique epigenomeGene expression programsENCODE projectTranscribed regionsMulticellular organismsStart siteRepressed regionsActive marksMammalian developmentComplex proteinsEpigenomeTissue specificityTarget genesExpression programsCell typesIntegrated analysis
2020
Expanded encyclopaedias of DNA elements in the human and mouse genomes
Moore J, Purcaro M, Pratt H, Epstein C, Shoresh N, Adrian J, Kawli T, Davis C, Dobin A, Kaul R, Halow J, Van Nostrand E, Freese P, Gorkin D, Shen Y, He Y, Mackiewicz M, Pauli-Behn F, Williams B, Mortazavi A, Keller C, Zhang X, Elhajjajy S, Huey J, Dickel D, Snetkova V, Wei X, Wang X, Rivera-Mulia J, Rozowsky J, Zhang J, Chhetri S, Zhang J, Victorsen A, White K, Visel A, Yeo G, Burge C, Lécuyer E, Gilbert D, Dekker J, Rinn J, Mendenhall E, Ecker J, Kellis M, Klein R, Noble W, Kundaje A, Guigó R, Farnham P, Cherry J, Myers R, Ren B, Graveley B, Gerstein M, Pennacchio L, Snyder M, Bernstein B, Wold B, Hardison R, Gingeras T, Stamatoyannopoulos J, Weng Z. Expanded encyclopaedias of DNA elements in the human and mouse genomes. Nature 2020, 583: 699-710. PMID: 32728249, PMCID: PMC7410828, DOI: 10.1038/s41586-020-2493-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChromatinDatabases, GeneticDeoxyribonuclease IDNADNA FootprintingDNA MethylationDNA Replication TimingGenomeGenome, HumanGenomicsHistonesHumansMiceMice, TransgenicMolecular Sequence AnnotationRegistriesRegulatory Sequences, Nucleic AcidRNA-Binding ProteinsTranscription, GeneticTransposasesConceptsMouse genomeCandidate cis-regulatory elementsCis-regulatory elementsDNA Elements (ENCODE) projectMouse fetal developmentChromatin structureGene regulationRespective genomesCellular contextDNA elementsDNA methylationENCODE dataTranscription factorsRNA transcriptionWeb-based serverGenomeExpansive resourceRNAEncyclopediaProteinFetal developmentChromatinTranscriptionHumansMethylationLogoJS: a Javascript package for creating sequence logos and embedding them in web applications
Pratt H, Weng Z. LogoJS: a Javascript package for creating sequence logos and embedding them in web applications. Bioinformatics 2020, 36: 3573-3575. PMID: 32181813, PMCID: PMC7267833, DOI: 10.1093/bioinformatics/btaa192.Peer-Reviewed Original ResearchConceptsWeb applicationJavaScript packagesSequence logosUser interface frameworkWeb-based visualization toolHuman-readable formatModern web technologiesUser interfaceWeb technologiesNeural networkOperating systemOpen-sourceVisualization toolsJavaScriptWeighted outputCompanion web applicationComputational techniquesWebConsensus sequenceGenomic dataSupplementary dataInteractive figuresMultiple lettersSequenceReactJSA curated benchmark of enhancer-gene interactions for evaluating enhancer-target gene prediction methods
Moore J, Pratt H, Purcaro M, Weng Z. A curated benchmark of enhancer-gene interactions for evaluating enhancer-target gene prediction methods. Genome Biology 2020, 21: 17. PMID: 31969180, PMCID: PMC6977301, DOI: 10.1186/s13059-019-1924-8.Peer-Reviewed Original ResearchConceptsEnhancer-gene interactionsTarget genesGene prediction methodsGenome-wide collectionCis-regulatory elementsCell typesEpigenomic dataDevelopment of computational methodsPredicted target genesGenomic interactionsPublished computational methodsTargetFinderComputational methodsGenesConclusionsOur resultsCCREsDistance methodCellsResultsToInteractionConclusionsOurTypePEPPrediction method
2018
Decoding the non-coding genome: Opportunities and challenges of genomic and epigenomic consortium data
Pratt H, Weng Z. Decoding the non-coding genome: Opportunities and challenges of genomic and epigenomic consortium data. Current Opinion In Systems Biology 2018, 11: 82-90. DOI: 10.1016/j.coisb.2018.09.002.Peer-Reviewed Original ResearchGenome-wide chromatin structureNext-generation sequencing dataCellular responses to stimuliFeatures of gene regulationUniform data processingNon-coding genomeTranscription factor bindingCell type differentiationIntegrated analysisGene expression changesSequence dataChromatin structureFactor bindingGene regulationOrganismal developmentTranscriptional activityExpression changesPhenotypic changesResponse to stimuliConsortium dataDisease mechanismsType differentiationComputational analysisInternational consortiumGenomeDifferential analysis of chromatin accessibility and histone modifications for predicting mouse developmental enhancers
Fu S, Wang Q, Moore J, Purcaro M, Pratt H, Fan K, Gu C, Jiang C, Zhu R, Kundaje A, Lu A, Weng Z. Differential analysis of chromatin accessibility and histone modifications for predicting mouse developmental enhancers. Nucleic Acids Research 2018, 46: 11184-11201. PMID: 30137428, PMCID: PMC6265487, DOI: 10.1093/nar/gky753.Peer-Reviewed Original ResearchConceptsPeak callersH3K27ac peaksDevelopmental enhancersHistone modificationsDistal cis-regulatory elementsAnalysis of chromatin accessibilityChIP-seq peaksPeak-calling algorithmsDepleted of nucleosomesCis-regulatory elementsModulate gene expressionTransgenic mouse assaysF-SeqDNase-seqHeart enhancersChromatin accessibilityH3K27ac signalH3K27acDNaseGene expressionHistoneDNase peakMouse assayPredicted enhancersDistant tissues
2017
HELZ2 Is an IFN Effector Mediating Suppression of Dengue Virus
Fusco D, Pratt H, Kandilas S, Cheon S, Lin W, Cronkite D, Basavappa M, Jeffrey K, Anselmo A, Sadreyev R, Yapp C, Shi X, O'Sullivan J, Gerszten R, Tomaru T, Yoshino S, Satoh T, Chung R. HELZ2 Is an IFN Effector Mediating Suppression of Dengue Virus. Frontiers In Microbiology 2017, 8: 240. PMID: 28265266, PMCID: PMC5316548, DOI: 10.3389/fmicb.2017.00240.Peer-Reviewed Original ResearchChromatin immunoprecipitation-sequencingFunctional genomic screensIFN antiviral responseNuclear receptor interaction proteinIFN signal transductionAntiviral effector genesDengue virusReceptor-interacting proteinHost response to viral infectionHost IFN signalingIFN-stimulated genesResponse to viral infectionGenomic screeningEffector genesInteracting proteinsInfectious dengue virusISRE elementKnockdown cellsAnti-dengue activityCo-immunoprecipitationGene productsSignal transductionTranscriptional programsAntiviral effect of IFNAntiviral effectors