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
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 ResearchMeSH KeywordsAnimalsGene ExpressionGenetic VariationGenome, HumanHumansImmunity, InnateInflammationNeanderthalsConceptsCis-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
2020
Massively parallel discovery of human-specific substitutions that alter enhancer activity
Uebbing S, Gockley J, Reilly SK, Kocher AA, Geller E, Gandotra N, Scharfe C, Cotney J, Noonan JP. Massively parallel discovery of human-specific substitutions that alter enhancer activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 118: e2007049118. PMID: 33372131, PMCID: PMC7812811, DOI: 10.1073/pnas.2007049118.Peer-Reviewed Original ResearchConceptsHuman-specific substitutionsHuman-gained enhancersGenetic changesEnhancer functionEnhancer activityHuman-specific genetic changesHuman evolutionGene regulatory elementsBackground genetic variationAncestral functionRegulatory evolutionEnhancer assaysGenetic variationRegulatory elementsNeural stem cellsHuman traitsNovel activityNonadditive wayRegulatory activityStem cellsFunctional impactDifferential activityParallel discoveryEnhancerEvolution