A massively parallel synthetic gene atlas for learning compact cis-regulatory grammar across cellular contexts
Virtual-cell models increasingly learn from large perturbation atlases, but their view of cis regulation remains limited to endogenous genes embedded in broad native regulatory contexts. Here we introduce Therna Biosciences' Chronos platform and its first public dataset release, comprising two complementary modules of a massively parallel synthetic gene atlas: Penta-47x27K for 5'…
The Therna Biosciences Chronos platform unveils a groundbreaking massively parallel synthetic gene atlas, consisting of two key modules. The Penta-47x27K dataset focuses on 5' UTRs/internal-promoter elements, while Tria-47x28K examines 3' UTR stability elements. Collectively, these datasets analyze around 60,000 compact cis-regulatory elements across approximately 50 cell lines in a single experiment.
The cells were generously provided by Tahoe Tx to enhance the dataset's utility for the virtual-cell modeling community. Therna applies its RNA-Logix(TM) platform, including Chronos, to various systems like primary cells and organoids through LNP-formulated mRNA delivery. Chronos captures both transcriptional and post-transcriptional gene expression control.
Using episomal DNA delivery, it measures DNA-normalized mRNA output, while direct RNA delivery with longitudinal sampling precisely quantifies RNA decay. Employing chemically modified synthetic mRNA with N1-methylpseudouridine, Chronos can resolve high-complexity libraries of up to 30,000 elements. By introducing synthetic genes with a defined and short regulatory code, Chronos expands gene regulatory networks, offering a valuable auxiliary cis-regulatory perspective for virtual-cell modeling and enabling the direct learning of context-specific cis-trans regulatory interactions.
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