Mapping Genetically Compensatory Pathways from Synthetic Lethal Interactions in Yeast

Background: Synthetic lethal genetic interaction analysis has been successfully applied to predicting the functions of genes and their pathway identities. In the context of synthetic lethal interaction data alone, the global similarity of synthetic lethal interaction patterns between two genes is used to predict gene function. With physical interaction data, such as proteinprotein interactions, the enrichment of physical interactions within subsets of genes and the enrichment of synthetic lethal interactions between those subsets of genes are used as an indication of compensatory pathways. Result: In this paper, we propose a method of mapping genetically compensatory pathways from synthetic lethal interactions. Our method is designed to discover pairs of gene-sets in which synthetic lethal interactions are depleted among the genes in an individual set and where such gene-set pairs are connected by many synthetic lethal interactions. By its nature, our method could select compensatory pathway pairs that buffer the deleterious effect of the failure of either one, without the need of physical interaction data. By focusing on compensatory pathway pairs where genes in each individual pathway have a highly homogenous cellular function, we show that many cellular functions have genetically compensatory properties. Conclusion: We conclude that synthetic lethal interaction data are a powerful source to map genetically compensatory pathways, especially in systems lacking physical interaction information, and that the cellular function network contain

Ten-year all-cause mortality according to smoking status in patients with severe coronary artery disease undergoing surgical or percutaneous revascularization

Aims To evaluate the impact of various smoking status on 10-year all-cause mortality and to examine a relative treatment benefit of coronary artery bypass grafting (CABG) vs. percutaneous coronary intervention (PCI) according to smoking habits. Methods and results The SYNTAX Extended Survival study evaluated vital status up to 10 years in 1800 patients with de novo three-vessel disease and/or left main coronary artery disease randomized to CABG or PCI in the SYNTAX trial. In the present analysis, patients were divided into three groups (current, former, or never smokers), and the primary endpoint of 10-year all-cause mortality was assessed according to smoking status. Smoking status was available in 1793 (99.6%) patients at the time of randomization, of whom 363 were current smokers, 798 were former smokers, and 632 were never smokers. The crude rates of 10-year all-cause mortality were 29.7% in current smokers, 25.3% in former smokers, and 25.9% in never smokers (Log-rank P = 0.343). After adjustment for imbalances in baseline characteristics, current smokers had a significantly higher risk of 10-year all-cause mortality than never smokers [adjusted hazard ratio (aHR): 2.29; 95% confidence interval (CI): 1.60-3.27; P < 0.001], whereas former smokers did not. PCI was associated with a higher risk of all-cause mortality than CABG among current smokers (HR: 1.60; 95% CI: 1.09-2.35; P = 0.017), but it failed to show a significant interaction between revascularization strategies and smoking status (P-interaction = 0.910). Conclusion Current smokers had a higher adjusted risk of 10-year all-cause mortality, whereas former smokers did not. The treatment effect of CABG vs. PCI did not differ significantly according to smoking status

Twenty-year outcomes of minimally invasive direct coronary artery bypass surgery: The Leipzig experience

Objective: Minimally invasive direct coronary artery bypass (MIDCAB) surgery involving left anterior descending coronary artery grafting with the left internal thoracic artery through a left anterior small thoracotomy is being routinely performed in some specified centers for patients with isolated complex left anterior descending coronary artery disease, but very few reports regarding long-term outcomes exist in literature. Our study was aimed at assessing and analyzing the early and long-term outcomes of a large cohort of patients who underwent MIDCAB procedures and identifying the effects of changing trends in patient characteristics on early mortality. Methods: A total of 2667 patients, who underwent MIDCAB procedures between 1996 and 2018, were divided into 3 groups on the basis of the year of surgery: group A, 1996-2003 (n = 1333); group B, 2004-2010 (n = 627) and group C, 2011-2018 (n = 707). Groupwise characteristics and early postoperative outcomes were compared. Long-term survival for all patients was analyzed and predictors for late mortality were identified using Cox proportional hazards methods. Results: The mean age was 64.5 ± 10.9 years and 691 (25.9%) patients were female. Group C patients (log EuroSCORE I = 4.9 ± 6.9) were older with more cardiac risk factors and comorbidities than groups A (log EuroSCORE I = 3.1 ± 4.5) and B (log EuroSCORE I = 3.5 ± 4.7). Overall and groupwise in-hospital mortality was 0.9%, 1.0%, 0.6%, and 1.0% (P = .7), respectively. Overall 10-, 15-, and 20-year survival estimates for all patients were 77.7 ± 0.9%, 66.1 ± 1.2%, and 55.6 ± 1.6%, respectively. Conclusions: MIDCAB can be safely performed with very good early and long-term outcomes. In-hospital mortality remained constant over the 22-year period of the study despite worsening demographic profile of patients