The extent to which JAK/STAT cytokine signaling is functionally redundant or selective remains debated. Here we engineered a “double” orthogonal IL-2/IL-2Rβ/γc ternary system enabling programmable, interference-free activation of each of the 36 mammalian cytokine receptors, and their downstream six STATs, in T cells. A...
This work presents a variant-agnostic approach to rescue haploinsufficiency by mapping and rationally redesigning the MYBPC3 promoter and identifies synergistic sequence edits that drive robust increases in MYBPC3 expression.
Aaron Renberg, S. Coppersmith, Owen Merritt et al.· bioRxiv· 0 citations
This work proposes a 'collective maintenance' model in which motif vocabularies defining cell type families are evolutionarily stable, while recombination of these motifs generates cell type-specific regulatory programmes.
Chew Chai, Jesse Gibson, Peng-Yang Li et al.· Nature Ecology & Evolution· 1 citation
A large-scale lentiMPRA in human excitatory neurons is performed, quantifying the impact of >46,000 naturally occurring variants across >27,000 candidate CREs near 524 disease-associated genes, establishing a large-scale functional variant catalog and providing a complementary benchmark and resource for developing and...
Kilian Salomon, Chengyu Deng, P. Dash et al.· bioRxiv· 0 citations
A biologically informed framework for classifying and interpreting chromatin interactions is developed and dual-state regulatory elements connected to these dual-state regulatory elements are enriched for developmental and signaling pathways and exhibit increased expression specificity across cell types, consistent wit...
A family of classification models, scE2G, is introduced that predict enhancer–gene regulatory interactions from single-cell datasets and enable mapping of these interactions across diverse cell types and tissues and will enable accurate mapping of enhancer–gene regulatory interactions across thousands of human cell typ...
Maya U. Sheth, Wei-Lin Qiu, X. Ma et al.· Nature Genetics· 1 citation
An encyclopedia of enhancer–gene regulatory interactions in the human genome is built, revealing global properties of enhancer networks, identifying differences in regulatory complexity across genes, and improving analyses linking noncoding variants to target genes and cell types for common, complex diseases.
A. Gschwind, Kristy S. Mualim, Alireza Karbalayghareh et al.· Nature· 6 citations
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