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Gene Network Identification and Integration (GNetii) Approach to Understanding the Biology Underlying HIV and Drug Abuse.

Award Number: R01DA051908
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY/ABSTRACT The goal of the proposed study is to advance our understanding of the complex networks of biology underlying variation in HIV viral load (VL) and latent reservoir (LR) among HIV+ individuals, and how cocaine abuse (CA) affects identified biological networks. With the success of combination antiretroviral therapy (cART) and public health strategies to reduce HIV incidence, much of the HIV burden in developed countries is now as a chronic disease, including among drug users. Managing HIV progression (HP) and searching for an HIV cure are of paramount importance. Higher pretreatment VL is associated with HP and is associated with a larger LR. An HIV cure is dependent on eliminating the LR. Cocaine is one of the most frequently abused illicit drugs among HIV+ individuals and is known to increase VL, worsen HP, slow decline of viral production after cART, and, we hypothesize, affect the quantity of LR. Thus, there is a complex web of relationships among VL, LR, and CA, which are partially driven by and mediated through genetic susceptibility and gene regulation. As concluded by Le Cleric et al. (2019) in their recent review: “Only integrative approaches that combine all big data results and consider their complex interactions will allow us to capture the global picture of HIV molecular pathogenesis. This novel challenge will require large collaborative efforts and represents a huge open field for innovative bioinformatics approaches.” We propose Gene Network Identification and Integration (GNetii) as a multi-method, multi-omic framework for discovering and understanding the biology underlying HIV outcomes and the effect of CA. We will apply Explainable Artificial Intelligence, network mapping, and Lines-of-Evidence integration to existing genome-, methylome-, and transcriptome-wide data across a number of cohorts in the following aims:  Aim 1: Identify gene networks underlying variation in HIV VL and LR applying GNetii.  Aim 2: Identify differences in HIV associated gene networks by CA. This robustly designed study is significant and innovative: targeting key HIV outcomes affected by CA, applying big data techniques to identify gene networks across multiple omics (enhancing discovery and biological interpretation), and leveraging unique LR data. Our multiple Principal Investigator team includes expertise in HIV, drug abuse, and computational biology. Thus, we are likely to produce important new insights into key elements of HIV as a chronic disease: providing a basis for targeting unique features of CA that impact VL and LR, which make HIV management and a cure more challenging in this population.


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: 2024 ( Subtotal = $600,318 )
2024	2024	RESEARCH TRIANGLE INSTITUTE	3040 CORNWALLIS RD	DURHAM	NC	27709	DURHAM	USA	Drug Abuse and Addiction Research Programs	000	5	5/16/2024	NON-COMPETING CONTINUATION	$600,318
														Subtotal = $600,318

Issue Date FY: 2023 ( Subtotal = $766,296 )
2023	2023	RESEARCH TRIANGLE INSTITUTE	3040 E CORNWALLIS RD	RESEARCH TRIANGLE PARK	NC	27709	DURHAM	USA	Drug Abuse and Addiction Research Programs	001	4	6/16/2023	SUPPLEMENT FOR EXPANSION	$159,013
2023	2023	RESEARCH TRIANGLE INSTITUTE	3040 E CORNWALLIS RD	RESEARCH TRIANGLE PARK	NC	27709	DURHAM	USA	Drug Abuse and Addiction Research Programs	000	4	6/15/2023	NON-COMPETING CONTINUATION	$607,283
														Subtotal = $766,296

Issue Date FY: 2022 ( Subtotal = $772,966 )
2022	2022	RESEARCH TRIANGLE INSTITUTE	3040 E CORNWALLIS RD	RESEARCH TRIANGLE PARK	NC	27709	DURHAM	USA	Drug Abuse and Addiction Research Programs	000	3	6/1/2022	NON-COMPETING CONTINUATION	$614,306
2022	2022	RESEARCH TRIANGLE INSTITUTE	3040 E CORNWALLIS RD	RESEARCH TRIANGLE PARK	NC	27709	DURHAM	USA	Drug Abuse and Addiction Research Programs	001	3	8/26/2022	SUPPLEMENT FOR EXPANSION	$158,660
														Subtotal = $772,966

Issue Date FY: 2021 ( Subtotal = $622,685 )
2021	2021	RESEARCH TRIANGLE INSTITUTE	3040 E CORNWALLIS RD	RESEARCH TRIANGLE PARK	NC	27709	DURHAM	USA	Drug Abuse and Addiction Research Programs	000	2	5/25/2021	NON-COMPETING CONTINUATION	$622,685
														Subtotal = $622,685

Issue Date FY: 2020 ( Subtotal = $631,522 )
2020	2020	RESEARCH TRIANGLE INSTITUTE	3040 E CORNWALLIS RD	RESEARCH TRIANGLE PARK	NC	27709	DURHAM	USA	Drug Abuse and Addiction Research Programs	000	1	7/28/2020	NEW	$631,522
														Subtotal = $631,522

Grand Total All Awards = $3,393,787

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Gene Network Identification and Integration (GNetii) Approach to Understanding the Biology Underlying HIV and Drug Abuse.

Award Number: R01DA051908

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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