Fig. 1: Damaging chromatin and cilia genotypes predict adverse post-operative outcomes in the context of CHD phenotypes and surgical complexity.
From: Genome sequencing is critical for forecasting outcomes following congenital cardiac surgery
Bayesian networks display a best machine-learned relationship among genotypes, phenotypes, and outcomes for 2253 surgical patients with CHD. Each network node represents a present/absent variable. Damaging genotypes in chromatin-modifying genes (CHRMdGV) or cilia-related genes (CILIAdGV) were identified from the exomes of 2253 CHD patients by GEM. Phenotype classes were predicted from Fyler codes using XGBoost. Surgical outcomes for each patient were obtained from the Society of Thoracic Surgeons national database. Relative risks for selected adverse surgical outcomes were then estimated from each network using network-propagated probabilities. a An exact Bayesian network depicting the relationship among damaging de novo genetic variants in chromatin-modifying genes (green), phenotypes: LVO, HLHS, and ECAs (blue), surgical STAT4 or STAT5 category (yellow), and adverse surgical outcomes (orange). b An exact Bayesian network depicting the relationship among damaging recessive genetic variants in cilia-related genes (green), phenotypes: laterality defects (HTX) and extra cardiac anomalies (ECAs) (blue), surgical STAT4 category (yellow), and adverse surgical outcomes: long ventilation time, cardiac arrest, and mortality (orange). Directed acyclic graphs were moralized and displayed as non-directional networks. c Relative risk ratio estimates for adverse post-operative outcomes and CHD phenotypes or surgical complexity, comparing probands with and without damaging genotypes. Empirical ninety-five percent confidence intervals (CI 5, 95) are based on 1000 resampled network-based probability estimates. Because the resampling distribution estimates may be constrained by the Bayesian network structure, error bars may not be symmetric with respect to the median point estimate (see Methods). Abbreviations: CHRMdGV - de novo damaging genotypes in chromatin-modifying genes, LVO - left ventricular outflow tract obstruction, HLHS - hypoplastic left heart syndrome, CILIAdGV - biallelic damaging genotypes in cilia-related genes, ECA - extra cardiac anomaly, HTX - heterotaxy/laterality defects, MORT - mortality, STAT4 - surgical STAT4 category, STAT4-5 - surgical STAT 4 or STAT5 category, VENT - post-operative ventilation time >7 days. For Figs. 1c, 2, and 3, there were 8–35 patients in the conditional subsets and 1–5 patients in the target sets (see Supplementary Data 4).
