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Machine learning drives translational research from drug interactions to pharmacogenetics

Award Number: R01LM014199
ORGANIZATION: NATIONAL LIBRARY OF MEDICINE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2023
PERIOD OF PERFORMANCE END DATE: 02/29/2028

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Machine learning drives translational research from drug interactions to pharmacogenetics - Summary Drug-drug interactions (DDIs) and pharmacogenetics (PG) are leading causes of adverse drug events (ADEs), with one in four patients experiencing ADEs attributable to DDIs or PG. However, despite the intrinsic connection of their pharmacological mechanisms, DDI and PG are often studied separately. There is a significant need for more efficient and effective translational from DDI to PG research, and newly developed machine-learning (ML) and artificial-intelligence (AI) methods have made such research feasible. In our recent DDI knowledge-discovery study of 25 million PubMed abstracts, we used ML and natural-language-processing analyses for the first time to identify 986 DDI pairs with overlapping pharmacokinetic mechanisms and clinical evidence, from which we generated 137 new PG hypotheses regarding CYP2D6 and CYP3A. In this grant proposal, we will develop novel ML methods, including active learning that will allow human annotator involvement and knowledge base reasoning that relies on logical rules to represent pharmacological mechanisms. This proposal has three aims: (1) to develop an active-learning approach to perform DDI and PG information retrieval analysis from the literature; (2) to develop a joint information-extraction and knowledge- base-reasoning approach to perform DDI and PG information extraction analysis from the literature; and (3) (a) to examine whether CYP3A/CYP2C19 genetic polymorphisms are associated with omeprazole-induced myopathy, and (b) to develop a prioritization scheme to examine new PG hypotheses generated from the literature-based discovery analyses from Aims 1 and 2 using Vanderbilt University’s BioVU biobank. These PG findings will provide a valuable resource for the wider scientific community for potential prospective studies and contribute significantly to the improvement of precision medicine and clinical care.


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 = $615,836 )
2026	2026	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Medical Library Assistance	001	4	2/27/2026	NON-COMPETING CONTINUATION	$615,836
2026	2025	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Medical Library Assistance	000	3	1/21/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $615,836

Issue Date FY: 2025 ( Subtotal = $634,590 )
2025	2025	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Medical Library Assistance	000	3	2/19/2025	NON-COMPETING CONTINUATION	$571,131
2025	2025	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Medical Library Assistance	001	3	6/6/2025	NON-COMPETING CONTINUATION	$63,459
														Subtotal = $634,590

Issue Date FY: 2024 ( Subtotal = $619,022 )
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Medical Library Assistance	001	2	5/8/2024	NON-COMPETING CONTINUATION	$61,902
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Medical Library Assistance	000	2	2/16/2024	NON-COMPETING CONTINUATION	$557,120
														Subtotal = $619,022

Issue Date FY: 2023 ( Subtotal = $633,396 )
2023	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Medical Library Assistance	000	1	4/28/2023	NEW	$633,396
														Subtotal = $633,396

Grand Total All Awards = $2,502,844

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Machine learning drives translational research from drug interactions to pharmacogenetics

Award Number: R01LM014199

ORGANIZATION: NATIONAL LIBRARY OF MEDICINE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2023

PERIOD OF PERFORMANCE END DATE: 02/29/2028

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