103: Genome Sequencing Forecasts Outcomes After Congenital Cardiac Surgery

️ Episode 103: Genome Sequencing Forecasts Outcomes After Congenital Cardiac Surgery In this episode of PaperCast Base by Base, we explore how large-scale exome sequencing combined with explainable AI can predict adverse outcomes after surgery for congenital heart defects. Using a prospective cohort from the Pediatric Cardiac Genomics Consortium, the study links specific genetic pathways to real-world postoperative risks and shows how genomics sharpens clinical risk stratification. Study Highlights: A prospective observational cohort of 2,253 patients underwent whole-exome sequencing; variants were prioritized with an AI genome-interpretation tool, cardiac phenotypes were auto-classified, and Bayesian networks quantified risk. Damaging de novo variants in chromatin-modifying genes and recessive/biallelic genotypes in cilia-related genes were associated with higher probabilities of mortality, cardiac arrest, and prolonged ventilation, whereas their absence lowered risk. Effects were strongest in high-complexity surgeries and specific phenotypes—such as left-ventricular outflow tract obstruction/hypoplastic left heart for chromatin genes and heterotaxy for cilia genes—and were amplified by extra-cardiac anomalies. The framework delivers personalized, clinically relevant risk estimates that can inform pre-operative planning, including proactive respiratory strategies for patients with ciliary dysfunction. Conclusion: Genomic profiling at or before surgery can meaningfully refine outcome forecasts for children with complex CHD, supporting earlier, targeted interventions and more precise peri-operative care. Reference: Watkins WS, Hernandez EJ, Miller TA, et al. Genome sequencing is critical for forecasting outcomes following congenital cardiac surgery. Nature Communications. 2025;16:6365. https://doi.org/10.1038/s41467-025-61625-0   License: This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support: If you'd like to support Base by Base, you can make a one-time or monthly donation here: https://donate.stripe.com/bJe6oI2GD0co7oE9iWcMM00 On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Chapters (00:00:00) - Pediatric Cardiac Genomics: The Future of Personalized Medicine(00:06:53) - Heart Defects 7, Damaging Genotypes(00:13:27) - Genomic sequencing for congenital heart surgery

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