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Statistical pangenomics to study the effects of zoonotic exposure on the gut microbiome

Award Number: R21AI168679
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/25/2022
PERIOD OF PERFORMANCE END DATE: 04/30/2024

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Statistical pangenomics to study the effects of zoonotic exposure on the gut microbiome - Project Summary: Zoonotic diseases result from the spillover of pathogens from animal reservoirs to humans due to contact with animals or animal products. An estimated 60% of known infectious diseases and up to 75% of emerging infectious diseases are zoonotic in origin. Despite this, relatively little is known about the alterations to the human microbiome in persons with a high degree of close contact with animals on farms. We propose a study to understand the pathogenic and non- pathogenic effects of a high degree of livestock exposure. We will use shotgun metagenomics to investigate which bacteria colonize the human gut after zoonotic exposure, which bacteria are outcompeted by colonizers, and which bacteria adapt. To enable comparisons with respect to virulence, beneficial metabolic pathways and antibiotic resistance, we will develop novel statistical methods for bacterial pangenomics. Existing methods for bacterial pangenomics assume that all genomes are observed without error, which rarely is the case for metagenome- assembled genomes (MAGs). For example, MAGs may omit genes that are truly present in the target genome, or MAGs may contain erroneously observed genes. To address limitations of current methods, we will develop statistical methodology that adjusts for differential quality in gene-level comparisons of metagenome-assembled genomes. Additionally, we will develop guidelines for the design of shotgun sequencing experiments based on maximizing power to test hypotheses about associations with gene presence. Successful completion of these aims will increase our understanding of the mechanisms of transmission of zoonotic pathogens and commensals, and advance broadly applicable and essential methodology for comparing bacterial genomes.


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: 2023 ( Subtotal = $194,375 )
2023	2023	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Allergy and Infectious Diseases Research	000	2	4/19/2023	NON-COMPETING CONTINUATION	$194,375
														Subtotal = $194,375

Issue Date FY: 2022 ( Subtotal = $233,250 )
2022	2022	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Allergy and Infectious Diseases Research	000	1	5/25/2022	NEW	$233,250
														Subtotal = $233,250

Grand Total All Awards = $427,625

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Statistical pangenomics to study the effects of zoonotic exposure on the gut microbiome

Award Number: R21AI168679

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/25/2022

PERIOD OF PERFORMANCE END DATE: 04/30/2024

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