@misc{10481/93775,
year = {2024},
url = {https://hdl.handle.net/10481/93775},
abstract = {Pediatric obesity can drastically heighten the risk of cardiometabolic alterations later in life, with insulin
resistance standing as the cornerstone linking adiposity to the increased cardiovascular risk. Puberty has been
pointed out as a critical stage after which obesity-associated insulin resistance is more difficult to revert. Timely
prediction of insulin resistance in pediatric obesity is therefore vital for mitigating the risk of its associated
comorbidities. The construction of effective and robust predictive systems for a complex health outcome like
insulin resistance during the early stages of life demands the adoption of longitudinal designs for more causal
inferences, and the integration of factors of varying nature involved in its onset. In this work, we propose
an eXplainable Artificial Intelligence-based decision support pipeline for early diagnosis of insulin resistance
in a longitudinal cohort of 90 children. For that, we leverage multi-omics (genomics and epigenomics) and
clinical data from the pre-pubertal stage. Different data layers combinations, pre-processing techniques (missing values, feature selection, class imbalance, etc.), algorithms, training procedures were considered following good practices for Machine Learning. SHapley Additive exPlanations were provided for specialists to understand both the decision-making mechanisms of the system and the impact of the features on each automatic decision, an essential issue in high-risk areas such as this one where system decisions may affect people’s lives. The system showed a relevant predictive ability (AUC and G-mean of 0.92). A deep exploration, both at the global and the local level, revealed promising biomarkers of insulin resistance in our population, highlighting classical markers, such as Body Mass Index z-score or leptin/adiponectin ratio, and novel ones such as methylation patterns of relevant genes, such as HDAC4, PTPRN2, MATN2, RASGRF1 and EBF1. Our findings highlight the importance of integrating multi-omics data and following eXplainable Artificial Intelligence trends when building decision support systems},
organization = {Department of Biochemistry and Molecular Biology II, School of Pharmacy, ‘‘José Mataix Verdú’’ Institute of Nutrition and Food Technology (INYTA) and Center of Biomedical Research, University of Granada, Granada, 18071, Spain},
keywords = {Pediatric obesity},
keywords = {Insulin resistance},
keywords = {Epigenomics},
keywords = {Multiomics},
keywords = {Machine Learning},
keywords = {Explainable Artificial Intelligence},
title = {Multiomics and eXplainable artificial intelligence for decision support in insulin resistance early diagnosis: A pediatric population-based longitudinal study},
doi = {10.1016/j.artmed.2024.102962},
author = {Torres-Martos, Álvaro and Anguita-Ruiz, Augusto and Bustos-Aibar, Mireia and Ramírez-Mena, Alberto and Arteaga, María and Bueno, Gloria and Leis, Rosaura and Aguilera García, Concepción María and Alcalá Fernández, Rafael and Alcalá-Fdez, Jesús},
}