2024
Machine-guided design of cell-type-targeting cis-regulatory elements
Gosai S, Castro R, Fuentes N, Butts J, Mouri K, Alasoadura M, Kales S, Nguyen T, Noche R, Rao A, Joy M, Sabeti P, Reilly S, Tewhey R. Machine-guided design of cell-type-targeting cis-regulatory elements. Nature 2024, 634: 1211-1220. PMID: 39443793, PMCID: PMC11525185, DOI: 10.1038/s41586-024-08070-z.Peer-Reviewed Original ResearchConceptsCis-regulatory elementsCell typesActivation of off-target cellsGene expressionCell type-specific expressionSynthetic cis-regulatory elementsCell-type specificityHuman genomeUnique cell typeTissue identityBiotechnological applicationsTissue specificityIn vitro validationCell linesCre activitySequenceGenesNatural sequenceDevelopmental timeExpressionCellsGenomeTested in vivoMotifOff-target cellsSomatic 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 brainVariantsMassively parallel approaches for characterizing noncoding functional variation in human evolution
Rong S, Root E, Reilly S. Massively parallel approaches for characterizing noncoding functional variation in human evolution. Current Opinion In Genetics & Development 2024, 88: 102256. PMID: 39217658, DOI: 10.1016/j.gde.2024.102256.Peer-Reviewed Original ResearchCis-regulatory elementsFunction of cis-regulatory elementsImpact of sequence variantsHigh-throughput approachNoncoding variationGenome functionNoncoding regionsSequence variantsPhenotypic consequencesCRISPR screensGenetic basisGenetic variantsGenetic differencesDiverse phenotypesGene expressionRegulatory functionsHuman evolutionFunctional variationGenomeUnique phenotypePhenotypeRegulatory impactModel systemVariantsGenes
2021
Detection of Neanderthal Adaptively Introgressed Genetic Variants That Modulate Reporter Gene Expression in Human Immune Cells
Jagoda E, Xue JR, Reilly SK, Dannemann M, Racimo F, Huerta-Sanchez E, Sankararaman S, Kelso J, Pagani L, Sabeti PC, Capellini TD. Detection of Neanderthal Adaptively Introgressed Genetic Variants That Modulate Reporter Gene Expression in Human Immune Cells. Molecular Biology And Evolution 2021, 39: msab304. PMID: 34662402, PMCID: PMC8760939, DOI: 10.1093/molbev/msab304.Peer-Reviewed Original ResearchConceptsCis-regulatory elementsGene expressionPutative cis-regulatory elementsParallel reporter assaysImmune transcription factorsReporter gene expressionExpression of genesGenic targetsSelective sweepsMPRA dataInnate immune pathwaysPositive selectionTranscription factorsEndogenous sequencesReporter assaysAntiviral defenseDriver variantsGenetic variantsFunctional significanceImmune pathwaysWhite blood cell countGenesModern humansPotential immune responseBlood cell count
2016
Direct Identification of Hundreds of Expression-Modulating Variants using a Multiplexed Reporter Assay
Tewhey R, Kotliar D, Park DS, Liu B, Winnicki S, Reilly SK, Andersen KG, Mikkelsen TS, Lander ES, Schaffner SF, Sabeti PC. Direct Identification of Hundreds of Expression-Modulating Variants using a Multiplexed Reporter Assay. Cell 2016, 165: 1519-1529. PMID: 27259153, PMCID: PMC4957403, DOI: 10.1016/j.cell.2016.04.027.Peer-Reviewed Original ResearchConceptsNon-coding variantsCausal allelesCis-expression quantitative trait lociReporter assaysHundreds of lociQuantitative trait lociParallel reporter assaysNon-coding polymorphismsTrait lociControl regionGene expressionRegulatory functionsDifferential expressionHuman traitsHuman biologyAlters expressionAllelesLociProstaglandin EP4 receptorTraitsExpressionRisk allelesVariantsDirect identificationDirect evidenceEvolution of Gene Regulation in Humans.
Reilly SK, Noonan JP. Evolution of Gene Regulation in Humans. Annual Review Of Genomics And Human Genetics 2016, 17: 45-67. PMID: 27147089, DOI: 10.1146/annurev-genom-090314-045935.Peer-Reviewed Original ResearchConceptsRegulatory functionsGene regulationHuman-specific genetic changesGenetic changesNovel human phenotypeNew regulatory functionInduced pluripotent stem cellsPluripotent stem cellsUnique biological featuresSpecific regulatory changesHomologous humanGenome editingGene expressionHuman phenotypesPrimate cellsHuman evolutionRegulatory activityStem cellsExpression levelsNonhuman primate cellsBiological featuresRegulationRegulatory innovationCellsHumans
2014
Evolution of Gene Regulation in Humans
Reilly S, Noonan J. Evolution of Gene Regulation in Humans. Annual Review Of Genomics And Human Genetics 2014, 17: 1-23. DOI: 10.1146/annurev-genom-090314-045935.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsRegulatory functionsGene regulationHuman-specific genetic changesGenetic changesNovel human phenotypeNew regulatory functionInduced pluripotent stem cellsPluripotent stem cellsUnique biological featuresSpecific regulatory changesHomologous humanGenome editingGene expressionHuman phenotypesFinal online publication datePrimate cellsHuman evolutionRegulatory activityStem cellsOnline publication dateExpression levelsNonhuman primate cellsBiological featuresRegulationRegulatory innovation