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 cells
2021
Genome-wide functional screen of 3′UTR variants uncovers causal variants for human disease and evolution
Griesemer D, Xue JR, Reilly SK, Ulirsch JC, Kukreja K, Davis JR, Kanai M, Yang DK, Butts JC, Guney MH, Luban J, Montgomery SB, Finucane HK, Novina CD, Tewhey R, Sabeti PC. Genome-wide functional screen of 3′UTR variants uncovers causal variants for human disease and evolution. Cell 2021, 184: 5247-5260.e19. PMID: 34534445, PMCID: PMC8487971, DOI: 10.1016/j.cell.2021.08.025.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesCausal variantsEvolutionary adaptationGenome-wide functional screenDiverse molecular mechanismsHuman evolutionary adaptationBase-pair resolutionParallel reporterHuman cell linesMiRNA sitesTranscriptional changesFunctional screenAllelic replacementSimple sequenceMolecular mechanismsAssociation studiesRich elementsPair resolutionHuman diseasesPhenotype associationsHuman traitsUntranslated region variantsGenetic variantsRegulatory activityCell lines
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 ResearchMeSH KeywordsAnimalsEvolution, MolecularGene Expression RegulationGenomeHumansInduced Pluripotent Stem CellsMiceMice, TransgenicPrimatesConceptsRegulatory 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