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Systematic analysis of bypass suppression of essential genes.

ABSTRACT: Essential genes tend to be highly conserved across eukaryotes, but, in some cases, their critical roles can be bypassed through genetic rewiring. From a systematic analysis of 728 different essential yeast genes, we discovered that 124 (17%) were dispensable essential genes. Through whole-genome sequencing and detailed genetic analysis, we investigated the genetic interactions and genome alterations underlying bypass suppression. Dispensable essential genes often had paralogs, were enriched for genes encoding membrane-associated proteins, and were depleted for members of protein complexes. Functionally related genes frequently drove the bypass suppression interactions. These gene properties were predictive of essential gene dispensability and of specific suppressors among hundreds of genes on aneuploid chromosomes. Our findings identify yeast's core essential gene set and reveal that the properties of dispensable essential genes are conserved from yeast to human cells, correlating with human genes that display cell line-specific essentiality in the Cancer Dependency Map (DepMap) project.

SUBMITTER: van Leeuwen J

PROVIDER: S-EPMC7507402 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Systematic analysis of bypass suppression of essential genes.

van Leeuwen Jolanda J Pons Carles C Tan Guihong G Wang Jason Zi JZ Hou Jing J Weile Jochen J Gebbia Marinella M Liang Wendy W Shuteriqi Ermira E Li Zhijian Z Lopes Maykel M Ušaj Matej M Dos Santos Lopes Andreia A van Lieshout Natascha N Myers Chad L CL Roth Frederick P FP Aloy Patrick P Andrews Brenda J BJ Boone Charles C

Molecular systems biology 20200901 9

Essential genes tend to be highly conserved across eukaryotes, but, in some cases, their critical roles can be bypassed through genetic rewiring. From a systematic analysis of 728 different essential yeast genes, we discovered that 124 (17%) were dispensable essential genes. Through whole-genome sequencing and detailed genetic analysis, we investigated the genetic interactions and genome alterations underlying bypass suppression. Dispensable essential genes often had paralogs, were enriched for ...[more]

PMID: 32939983

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Project description:ObjectiveA meta-analysis of randomized controlled trials was performed to compare the effects of miniaturized extracorporeal circulation (MECC) and conventional extracorporeal circulation (CECC) on morbidity and mortality rates after cardiac surgery.MethodsA comprehensive literature search was conducted using Ovid, PubMed, Medline, EMBASE, and the Cochrane databases. Randomized controlled trials from the year 2000 with n > 40 patients were considered. Key search terms included variations of "mini," "cardiopulmonary," "bypass," "extracorporeal," "perfusion," and "circuit." Studies were assessed for bias using the Cochrane Risk of Bias tool. The primary outcomes were postoperative mortality and stroke. Secondary outcomes included arrhythmia, myocardial infarction, renal failure, blood loss, and a composite outcome comprised of mortality, stroke, myocardial infarction and renal failure. Duration of intensive care unit, and hospital stay was also recorded.ResultsThe 42 studies eligible for this study included a total of 2154 patients who underwent CECC and 2196 patients who underwent MECC. There were no significant differences in any preoperative or demographic characteristics. Compared with CECC, MECC did not reduce the incidence of mortality, stroke, myocardial infarction, and renal failure but did significantly decrease the composite of these outcomes (odds ratio, 0.64; 95% confidence interval [CI], 0.50-0.81; P = .0002). MECC was also associated with reductions in arrhythmia (odds ratio, 0.67; 95% CI, 0.54-0.83; P = .0003), blood loss (mean difference [MD], -96.37 mL; 95% CI, -152.70 to -40.05 mL; P = .0008), hospital stay (MD, -0.70 days; 95% CI, -1.21 to -0.20 days; P = .006), and intensive care unit stay (MD, -2.27 hours; 95% CI, -3.03 to -1.50 hours; P < .001).ConclusionsMECC demonstrates clinical benefits compared with CECC. Further studies are required to perform a cost-utility analysis and to assess the long-term outcomes of MECC. These should use standardized definitions of endpoints such as mortality and renal failure to reduce inconsistency in outcome reporting.

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Systematic analysis of bypass suppression of essential genes.

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Systematic analysis of bypass suppression of essential genes.

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