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Inferring Molecular Mechanisms of Complex Disease by Integrating Patterns of Epistasis with Functional Genomic Networks

Award Number: R21LM012615
ORGANIZATION: NATIONAL LIBRARY OF MEDICINE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/05/2018
PERIOD OF PERFORMANCE END DATE: 05/31/2021

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Inferring Molecular Mechanisms of Complex Disease by Integrating Patterns of Epistasis with Functional Genomic Networks - The goal of this proposal is to develop computational methods that will identify genes driving epistasis between quantitative trait loci. Genetic association studies in both humans and model organisms have been increasingly able to detect interactions among genetic variants that influence disease risk and pathogenesis. However, identifying which genes are represented by individual variants is a major challenge. Many variants influencing disease are situated between genes, and even those that are in genes may be representing an effect from a neighboring gene. In model organism studies the situation is even more problematic. In breeding experiments, genetic associations with phenotypes typically encompass large regions of DNA with many genes, and experimental follow-up to identify the genes responsible for the association is resource-intensive. To address this problem, we are developing computational tools to prioritize putative gene interactions in interacting genomic regions for biological follow-up. We use machine learning classifiers trained on functional gene-gene interaction networks and combinatorial optimization to identify likely candidate gene-gene interactions responsible for epistatic interactions between genomic regions. Our methods sift through enormous spaces of candidate interactions, retaining only those whose functional interactions identify as plausible for supporting the epistatic interaction. These tools hold promise to dramatically limit the resource-intensity of biological follow up of putative epistasis and to clarify the genetic architecture of complex disease.


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: 2021 ( Subtotal = $0 )
2021	2019	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Medical Library Assistance	000	2	8/25/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $218,175 )
2019	2019	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Medical Library Assistance	000	2	5/2/2019	NON-COMPETING CONTINUATION	$227,700
2019	2019	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Medical Library Assistance	002	2	7/4/2019	NON-COMPETING CONTINUATION	-$4,500
2019	2018	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Medical Library Assistance	001	1	7/3/2019	NEW	-$5,025
														Subtotal = $218,175

Issue Date FY: 2018 ( Subtotal = $205,200 )
2018	2018	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Medical Library Assistance	000	1	6/5/2018	NEW	$205,200
														Subtotal = $205,200

Grand Total All Awards = $423,375

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Inferring Molecular Mechanisms of Complex Disease by Integrating Patterns of Epistasis with Functional Genomic Networks

Award Number: R21LM012615

ORGANIZATION: NATIONAL LIBRARY OF MEDICINE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/05/2018

PERIOD OF PERFORMANCE END DATE: 05/31/2021

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