NSF Org:	DBI Div Of Biological Infrastructure
Recipient:	WILLIAM MARSH RICE UNIVERSITY
Initial Amendment Date:	February 28, 2022
Latest Amendment Date:	February 28, 2022
Award Number:	2144534
Award Instrument:	Continuing Grant
Program Manager:	Jennifer Weller jweller@nsf.gov  (703)292-2224 DBI  Div Of Biological Infrastructure BIO  Direct For Biological Sciences
Start Date:	March 1, 2022
End Date:	February 28, 2027 (Estimated)
Total Intended Award Amount:	$794,249.00
Total Awarded Amount to Date:	$610,097.00
Funds Obligated to Date:	FY 2022 = $610,097.00
History of Investigator:	Vicky Yao (Principal Investigator) vy@rice.edu
Recipient Sponsored Research Office:	William Marsh Rice University 6100 MAIN ST Houston TX  US  77005-1827 (713)348-4820
Sponsor Congressional District:	09
Primary Place of Performance:	William Marsh Rice University 6100 MAIN ST Houston TX  US  77005-1827
Primary Place of Performance Congressional District:	09
Unique Entity Identifier (UEI):	K51LECU1G8N3
Parent UEI:
NSF Program(s):	Innovation: Bioinformatics, Cross-BIO Activities
Primary Program Source:	01002223DB NSF RESEARCH & RELATED ACTIVIT 010V2122DB R&RA ARP Act DEFC V
Program Reference Code(s):	102Z, 1045, 1165, 7218, 9251
Program Element Code(s):	164Y00, 727500
Award Agency Code:	4900
Fund Agency Code:	4900
Assistance Listing Number(s):	47.074

ABSTRACT

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2).

DNA methylation is a critical biological process that plays such an important role in gene regulation that it has often been referred to as the ?fifth base of DNA.? In addition to playing an important role during development and throughout aging, aberrations in DNA methylation have been discovered to cause disease, including cancer and neurological disorders. Yet much is still unknown regarding where DNA methylation changes occur and which genes they impact. This, coupled with its dynamic nature, which can vary across regions of the body, throughout the life cycle, and in response to the environment, makes accurately identifying the association of specific methylation patterns to biological phenomena of interest and interpreting their downstream impacts challenging. The project will result in a suite of new tools to enable analysis of methylation sites across experimental technologies, analyze methylation data in the context of different tissues and cell types, and predict the downstream impacts of methylation sites that are changing across conditions. These tools will enable researchers to better interpret their methylation data in light of existing knowledge, which can in turn result in improved understanding of fundamental biological processes (e.g., development, aging). In addition to making all methods available as open-source software, databases of predictions and interactive visualizations will be developed and accessible online. By doing so, biological researchers with no programming experience can use a query-based system to easily make and explore predictions in the context of their own data. This project also has a local outreach component to help increase the diversity and persistence of underrepresented minorities in STEM by engaging high school biology teachers and community college students with newly designed data driven curricula as well as research opportunities.

The research will adapt cutting edge deep learning methods used for imputation in other domains to increase the coverage of DNA methylation platforms that profile <10% of all sites, saving time and resources; use a hierarchical framework that mirrors natural tissue and cell type dependencies to find location-specific methylation hallmarks; and incorporate known protein-protein interactions to associate CpG sites with biological function, beyond existing methods which primarily capture proximal regulatory relationships. In addition to the methodological contributions of this work, the project is inherently interdisciplinary and will lay the groundwork for understanding fundamental biological questions such as how methylation regulates and maintains tissue specificity. The tools and results from this project can be found at: https://cs.rice.edu/~vy/.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

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