Genome sequencing is critical for forecasting outcomes following congenital cardiac surgery

Figures

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  Fig. 1. Damaging chromatin and cilia genotypes predict adverse post-operative outcomes in the context of CHD phenotypes and surgical complexity. 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…

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  Fig. 2. Damaging chromatin and cilia genotypes predict adverse post-operative outcomes in the context of extracardiac anomalies. Relative risk ratios for adverse post-operative outcomes and extracardiac anomalies (ECAs), comparing probands with and without damaging genotypes in chromatin-modifying or cilia-related genes. Each risk estimate shows the point estimate of the network propagated relative risk. Empirical ninety-five percent confidence intervals (CI 5, 95) were generated by resampling the data matrix with replacement and re-estimating the network propagated risk 1000 times. 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. Target and conditional counts are listed in Supplementary Data 4. The \\ symbol represents a (CI 5, 95) that exceeds the x-axis range.

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  Fig. 3. Damaging genotypes in various gene categories/pathways are predictive of mortality for the most complex surgical procedures. Relative risk ratios for adverse post-operative outcomes and surgical complexity compare probands with and without damaging genotypes in various gene pathways or categories. Gene lists are described in Supplementary Data 3 and have been previously published5,8,9. There is overlap between gene lists, with some genes represented in more than one gene pathway/category (Supplementary Fig. 4). Each estimate shows the point estimate of the network propagated relative risk. Empirical ninety-five percent confidence intervals (CI 5, 95) were generated by resampling the data matrix with replacement and re-estimating the network propagated risk 1,000 times. 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. Target and conditional counts are listed in Supplementary Data 4.