Noncoding variants and sulcal patterns in congenital heart disease: Machine learning to predict functional impact
Year: 2024
Type: article
Study design: Observational Study
Abstract: Summary Neurodevelopmental impairments associated with congenital heart disease (CHD) may arise from perturbations in brain developmental pathways, including the formation of sulcal patterns. While genetic factors contribute to sulcal features, the association of noncoding de novo variants (ncDNVs) with sulcal patterns in people with CHD remains poorly understood. Leveraging deep learning models, we examined the predicted impact of ncDNVs on gene regulatory signals. Predicted impact was compared between participants with CHD and a jointly called cohort without CHD. We then assessed the relationship of the predicted impact of ncDNVs with their sulcal folding patterns. ncDNVs predicted to increase H3K9me2 modification were associated with larger disruptions in right parietal sulcal patterns in the CHD cohort. Genes predicted to be regulated by these ncDNVs were enriched for functions related to neuronal development. This highlights the potential of deep learning models to generate hypotheses about the role of noncoding variants in brain development.
Source: iScience
Authors: Enrique Mondragon-Estrada, Jane W. Newburger, Steven R. DePalma, Martina Brueckner, John Cleveland, Wendy K. Chung, Bruce D. Gelb, Elizabeth Goldmuntz, Donald J. Hagler, Hao Huang, Patrick McQuillen, Thomas A. Miller, Ashok Panigrahy, George A. Porter, Amy E. Roberts, Caitlin K. Rollins, Mark W. Russell, Martin Tristani-Firouzi, P. Ellen Grant, Kiho Im, Sarah U. Morton
Institutions: Boston Children's Hospital, Harvard University, Yale University, University of Southern California, Icahn School of Medicine at Mount Sinai, Children's Hospital of Philadelphia, University of Pennsylvania, University of California San Diego, University of California, San Francisco, Primary Children's Hospital, Maine Medical Center, University of Utah, Maine Medical Center, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, University of Rochester Medicine, University of Rochester, University of Michigan, C. S. Mott Children's Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,150
Funders: American Heart Association, National Institutes of Health, National Heart, Lung, and Blood Institute, National Center for Research Resources, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Office of Intramural Training and Education
Awards: G1044130170, The Genetic Basis of Conotruncal Defects, G1415733790, G1649372110, G222509006, G2406557048, Genomic studies of secundum atrial septal defects, G2880790201, G2941241070, The Harvard Clinical and Translational Science Center, G322278547, G4875130423, G4880724714, G5289318276, G627991465, Administrative Coordinating Center: Bench to Bassinet Program, G742032275, Molecular approaches to gene identification in congenital heart disease, G9000045419, G9000066746, G9000067114, G9000189125, G9000213666, Boston Children's Hospital/HMS Intellectual and Developmental Disabilities Research Center, Yale Clinical and Translational Science Award
OpenAlex ID: W4405867594