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
Functional characterization of T2D-associated SNP effects on baseline and ER stress-responsive β cell transcriptional activation
Khetan S, Kales S, Kursawe R, Jillette A, Ulirsch JC, Reilly SK, Ucar D, Tewhey R, Stitzel ML. Functional characterization of T2D-associated SNP effects on baseline and ER stress-responsive β cell transcriptional activation. Nature Communications 2021, 12: 5242. PMID: 34475398, PMCID: PMC8413311, DOI: 10.1038/s41467-021-25514-6.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesSingle nucleotide polymorphismsTranscriptional activationEndoplasmic reticulum (ER) stress conditionsTranscriptional stress responseCis-regulatory effectsParallel reporter assaysT2D single nucleotide polymorphismsHigh linkage disequilibriumMultiple single nucleotide polymorphismsT2D genetic riskT2D-associated single nucleotide polymorphismsMIN6 β-cellsChromatin accessibilityCandidate single nucleotide polymorphismsT2D geneticsHuman genomeAssociation signalsRepetitive elementsFunctional characterizationNuclear elementsMolecular mechanismsReporter assaysStress responseAssociation studies