Explainable artificial intelligence for precision medicine in acute myeloid leukemia

Artificial intelligence (AI) can unveil novel personalized treatments based on drug screening and whole-exome sequencing experiments (WES). However, the concept of "black box" in AI limits the potential of this approach to be translated into the clinical practice. In contrast, explainable...

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Detalles Bibliográficos
Autores: Gimeno-Combarro, M. (Marian)|||/items/aee49dbe-e8c2-4ab3-bf3f-3129a14e3309, San-José-Enériz, E. (Edurne)|||/items/1c6714b1-f536-4b57-a755-83eca42e9964, Villar-Fernández, S. (Sara)|||/items/303f27b5-53ca-4de6-8dd6-02c655de7149, Prosper-Cardoso, F. (Felipe)|||/items/3d1b0b82-06c3-4e63-8280-e903dc4dc0c1, Rubio-Díaz-Cordovés, A. (Ángel)|||/items/7d740e1e-38db-46ea-9834-8c61aa6eedee, Carazo-Melo, F.(Fernando)|||/items/23abbe07-938d-434d-9483-864ef915f6b5, Aguirre-Ena, X. (Xabier)|||/items/2a000d9c-cb5c-4734-a32c-4fef79998c86
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/116520
Acceso en línea:https://hdl.handle.net/10171/116520
Access Level:acceso abierto
Palabra clave:Assignation problem
Biomarkers
Drug repositioning
Drug sensitivity
Ex-vivo experiment
Explainable artificial intelligence
Large-scale screening
Treatment selection
Descripción
Sumario:Artificial intelligence (AI) can unveil novel personalized treatments based on drug screening and whole-exome sequencing experiments (WES). However, the concept of "black box" in AI limits the potential of this approach to be translated into the clinical practice. In contrast, explainable AI (XAI) focuses on making AI results understandable to humans. Here, we present a novel XAI method -called multi-dimensional module optimization (MOM)- that associates drug screening with genetic events, while guaranteeing that predictions are interpretable and robust. We applied MOM to an acute myeloid leukemia (AML) cohort of 319 ex-vivo tumor samples with 122 screened drugs and WES. MOM returned a therapeutic strategy based on the FLT3, CBFβ-MYH11, and NRAS status, which predicted AML patient response to Quizartinib, Trametinib, Selumetinib, and Crizotinib. We successfully validated the results in three different large-scale screening experiments. We believe that XAI will help healthcare providers and drug regulators better understand AI medical decisions.