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High-throughput Discovery of Novel Genome Organization Regulators

Award Number: R03OD036495
ORGANIZATION: OFFICE OF THE DIRECTOR, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/20/2023
PERIOD OF PERFORMANCE END DATE: 09/19/2025

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High-throughput Discovery of Novel Genome Organization Regulators - ABSTRACT CTCF binding at its convergent-orientated DNA motifs has been implicated in establishing TAD boundary. CTCF protein regulates the genome organization through cohesin complex-mediated loop extrusion mechanism. While a few more factors have been recently discovered to regulate genome organization, such as NIPBL, WAPL, YY1, ZNF143, and MAZ, it is still far from a comprehensive mechanistic understanding of how the genome is organized. Discovering novel regulators of genome organization is still challenging due to the intensive nature of chromatin conformation capture technologies. To address the technical challenge in measuring genome organization, we have recently demonstrated that a deep neural network approach can enable de novo prediction of cell type- specific chromatin organization at high resolution. Moreover, this deep neural network model enables high- throughput in silico genetic screen (ISGS) for identifying cell type-specific DNA elements that are important for chromatin interactions. To fully unlock the discovery potential of this deep neural network-based ISGS approach, here we propose to leverage the NIH Common Fund-supported large-scale genomic data across human bio- samples for discovering novel regulators in 3D genome organization. We will predict a list of high-confidence trans-acting regulators, and experimentally validate 3-5 top hits in pilot studies to generate cross-cutting hypotheses for future research in 3D genome regulation.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2023	THE BROAD INSTITUTE, INC	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Trans-NIH Research Support	000	1	12/22/2025	NEW	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $292,728 )
2023	2023	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Trans-NIH Research Support	000	1	9/20/2023	NEW	$292,728
														Subtotal = $292,728

Grand Total All Awards = $292,728

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High-throughput Discovery of Novel Genome Organization Regulators

Award Number: R03OD036495

ORGANIZATION: OFFICE OF THE DIRECTOR, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/20/2023

PERIOD OF PERFORMANCE END DATE: 09/19/2025

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