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 cells
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 mapsGenesDNADiversityCopiesSequence
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 death
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 lettersSequenceReactJS
2013
Genome-wide Analysis of Immune System Genes by Expressed Sequence Tag Profiling
Giallourakis C, Benita Y, Molinie B, Cao Z, Despo O, Pratt H, Zukerberg L, Daly M, Rioux J, Xavier R. Genome-wide Analysis of Immune System Genes by Expressed Sequence Tag Profiling. The Journal Of Immunology 2013, 190: 5578-5587. PMID: 23616578, PMCID: PMC3703829, DOI: 10.4049/jimmunol.1203471.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCluster AnalysisComputational BiologyDatabases, Nucleic AcidDNA-Binding ProteinsExpressed Sequence TagsGene Expression ProfilingGene Regulatory NetworksGenome-Wide Association StudyGenomicsHumansImmune SystemImmune System DiseasesLymphoma, B-CellMiceMolecular Sequence AnnotationReproducibility of ResultsRNA, Long NoncodingTranscription FactorsTranscriptomeConceptsExpressed sequence tagsExpressed sequence tag profilingEncyclopedia of DNA ElementsHuman expressed sequence tagsGenome-wide analysisIdentification of transcriptsMicroarray-based studiesImmune system genesRNA sequencing analysisStudies of mRNADNA elementsSequence tagsNovel genesMetabolic gene signatureNoncoding genesSequence analysisTranscriptome analysisImmune systemMicroarray studiesOverexpressed genesSystem genesGene expressionGenesFunctional studiesNoncoding RNAs