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Interpretable deep learning models for translational medicine Renewal

Award Number: R01LM012011
ORGANIZATION: NATIONAL LIBRARY OF MEDICINE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2015
PERIOD OF PERFORMANCE END DATE: 05/31/2028

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Interpretable deep learning models for translational medicine Renewal - Abstract Conventional precision oncology concentrates on applying molecularly targeted drugs based on genomic markers from a tumor. Such a genome-informed approach has limitations, mainly because it covers around 15% of all cancer patients. While chemotherapies remain the backbone of oncology, their application is not personalized. In this study, we proposed to develop an advanced artificial intelligence (AI) framework for predicting cancer cell sensitivity to chemotherapies. We will apply the framework to solve a real-world clinical problem: guiding the precision application of oxaliplatin in treating colon cancer adjuvant therapy. Our framework consists of two phases: A representation-learning phase, which involves developing and applying advanced AI models that can infer and represent the state of cellular signaling systems of cancer cells by mining diverse omics data of cancers. A cell-state- oriented drug sensitivity prediction phase, which involves using advanced classification models to utilize the inferred cancer cell states to predict the drug response of different cancer cells. Importantly, we will address an unmet clinical need in treating colon cancer patients as a real-world use case. With estimated 1.9 million incidences, colorectal cancer (CRC) is the 3rd most common cancer and the 2nd leading cause of cancer death. Patients with resected high-risk stage II/III colon cancer (CC) receive adjuvant chemotherapy to prevent cancer recurrence. A regimen consisting of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is the standard of care for CC adjuvant therapy. It is estimated that including oxaliplatin in the regimen benefits 5% - 6% of patients but subjects ~90% of patients to life-impairing neurotoxicity. A significant effort in oncology is to identify the patients who would not benefit from oxaliplatin and save them from unnecessary side effects (de-escalation). In this study, we will collect large-scale omics data from colon cancer patients. We propose advanced causal discovery and deep learning to infer the state of signaling systems of cancer cells and further develop advanced individualized treatment effect prediction models to guide oxaliplatin treatment.


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: 2025 ( Subtotal = $337,832 )
2025	2025	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Medical Library Assistance	002	10	5/2/2025	NON-COMPETING CONTINUATION	$337,832
2025	2024	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Medical Library Assistance	000	9	3/7/2025	COMPETING CONTINUATION	$0
2025	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Medical Library Assistance	001	8	4/2/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $337,832

Issue Date FY: 2024 ( Subtotal = $353,140 )
2024	2024	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Medical Library Assistance	001	9	7/16/2024	COMPETING CONTINUATION	$353,140
2024	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Medical Library Assistance	000	8	7/8/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $353,140

Issue Date FY: 2023 ( Subtotal = $313,657 )
2023	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Medical Library Assistance	000	8	3/14/2023	NON-COMPETING CONTINUATION	$313,657
														Subtotal = $313,657

Issue Date FY: 2022 ( Subtotal = $312,719 )
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Medical Library Assistance	000	7	2/25/2022	NON-COMPETING CONTINUATION	$312,719
														Subtotal = $312,719

Issue Date FY: 2021 ( Subtotal = $309,404 )
2021	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Medical Library Assistance	000	6	3/12/2021	NON-COMPETING CONTINUATION	$293,933
2021	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Medical Library Assistance	001	6	5/14/2021	NON-COMPETING CONTINUATION	$15,471
														Subtotal = $309,404

Issue Date FY: 2020 ( Subtotal = $309,622 )
2020	2020	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Medical Library Assistance	000	5	5/26/2020	COMPETING CONTINUATION	$309,622
2020	2018	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Medical Library Assistance	001	4	6/22/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $309,622

Issue Date FY: 2018 ( Subtotal = $327,823 )
2018	2018	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Medical Library Assistance	000	4	5/8/2018	NON-COMPETING CONTINUATION	$327,823
														Subtotal = $327,823

Issue Date FY: 2017 ( Subtotal = $328,031 )
2017	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Medical Library Assistance	000	3	3/31/2017	NON-COMPETING CONTINUATION	$295,227
2017	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Medical Library Assistance	001	3	7/8/2017	NON-COMPETING CONTINUATION	$32,804
														Subtotal = $328,031

Issue Date FY: 2016 ( Subtotal = $328,232 )
2016	2016	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Medical Library Assistance	000	2	3/31/2016	NON-COMPETING CONTINUATION	$328,232
														Subtotal = $328,232

Issue Date FY: 2015 ( Subtotal = $343,551 )
2015	2015	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Medical Library Assistance	000	1	3/30/2015	NEW	$343,551
														Subtotal = $343,551

Grand Total All Awards = $3,264,011

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Interpretable deep learning models for translational medicine Renewal

Award Number: R01LM012011

ORGANIZATION: NATIONAL LIBRARY OF MEDICINE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2015

PERIOD OF PERFORMANCE END DATE: 05/31/2028

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