A massively parallel synthetic gene atlas for learning compact cis-regulatory grammar across cellular contexts
- 1Arc Institute
Abstract
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' UTRs/internal-promoter elements and Tria-47x28K for 3' UTR stability elements. Together, these datasets measure ~60,000 compact cis-regulatory elements across approximately 50 cell lines in one pooled experiment. The choice of cell lines here, provided to us courtesy of Tahoe Tx, was rooted in our aim to make this dataset maximally useful for the virtual-cell modeling community. At Therna, we routinely apply Chronos -- part of our RNA-Logix(TM) platform -- beyond cancer cell-line pools, to systems such as primary cells and organoids, via LNP-formulated mRNA delivery. Chronos captures both transcriptional and post-transcriptional gene expression control. Episomal DNA delivery measures DNA-normalized mRNA output, while direct RNA delivery with longitudinal sampling reliably quantifies RNA decay. The RNA-delivery arm uses chemically modified synthetic mRNA incorporating N1-methylpseudouridine, a modification widely used in mRNA therapeutics. To resolve high-complexity libraries of up to 30,000 elements, Chronos pushes the sensitivity limits of single-cell RNA sequencing to quantify individual RNA molecules within single cells. By massively expanding gene regulatory networks with synthetic genes whose variable regulatory code is short and defined, Chronos provides an auxiliary cis-regulatory lens for virtual-cell modeling and enables context-specific cis-trans regulatory interactions to be learned directly.
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BibTeX
@misc{hagen2026massively,
title = {{A massively parallel synthetic gene atlas for learning compact cis-regulatory grammar across cellular contexts}},
author = {T. Hagen and I. Liu and A. Nagainis and N. Khosrojerdi and H. Yousefi and T. Gunnels and A. Moarefi and K. Green and N. Azimi and A. Momen-Roknabadi and K. R. Kipp and H. Goodarzi},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.13.751267},
url = {https://www.biorxiv.org/content/10.64898/2026.09.13.751267v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A massively parallel synthetic gene atlas for learning compact cis-regulatory grammar across cellular contexts
AU - T. Hagen
AU - I. Liu
AU - A. Nagainis
AU - N. Khosrojerdi
AU - H. Yousefi
AU - T. Gunnels
AU - A. Moarefi
AU - K. Green
AU - N. Azimi
AU - A. Momen-Roknabadi
AU - K. R. Kipp
AU - H. Goodarzi
PY - 2026
DA - 2026/09/13
PB - bioRxiv
DO - 10.64898/2026.09.13.751267
UR - https://www.biorxiv.org/content/10.64898/2026.09.13.751267v1
AB - 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' UTRs/internal-promoter elements and Tria-47x28K for 3' UTR stability elements. Together, these datasets measure ~60,000 compact cis-regulatory elements across approximately 50 cell lines in one pooled experiment. The choice of cell lines here, provided to us courtesy of Tahoe Tx, was rooted in our aim to make this dataset maximally useful for the virtual-cell modeling community. At Therna, we routinely apply Chronos -- part of our RNA-Logix(TM) platform -- beyond cancer cell-line pools, to systems such as primary cells and organoids, via LNP-formulated mRNA delivery. Chronos captures both transcriptional and post-transcriptional gene expression control. Episomal DNA delivery measures DNA-normalized mRNA output, while direct RNA delivery with longitudinal sampling reliably quantifies RNA decay. The RNA-delivery arm uses chemically modified synthetic mRNA incorporating N1-methylpseudouridine, a modification widely used in mRNA therapeutics. To resolve high-complexity libraries of up to 30,000 elements, Chronos pushes the sensitivity limits of single-cell RNA sequencing to quantify individual RNA molecules within single cells. By massively expanding gene regulatory networks with synthetic genes whose variable regulatory code is short and defined, Chronos provides an auxiliary cis-regulatory lens for virtual-cell modeling and enables context-specific cis-trans regulatory interactions to be learned directly.
ER -