scholarly journals Genome-scale Reconstruction of Metabolic Network inBacillus subtilisBased on High-throughput Phenotyping and Gene Essentiality Data

2007 ◽  
Vol 282 (39) ◽  
pp. 28791-28799 ◽  
Author(s):  
You-Kwan Oh ◽  
Bernhard O. Palsson ◽  
Sung M. Park ◽  
Christophe H. Schilling ◽  
Radhakrishnan Mahadevan
2018 ◽  
Author(s):  
Anna S. Blazier ◽  
Jason A. Papin

AbstractThe identification of genes essential for bacterial growth and survival represents a promising strategy for the discovery of antimicrobial targets. Essential genes can be identified on a genome-scale using transposon mutagenesis approaches; however, variability between screens and challenges with interpretation of essentiality data hinder the identification of both condition-independent and condition-dependent essential genes. To illustrate the scope of these challenges, we perform a large-scale comparison of multiple published Pseudomonas aeruginosa gene essentiality datasets, revealing substantial differences between the screens. We then contextualize essentiality using genome-scale metabolic network reconstructions and demonstrate the utility of this approach in providing functional explanations for essentiality and reconciling differences between screens. Genome-scale metabolic network reconstructions also enable a high-throughput, quantitative analysis to assess the impact of media conditions on the identification of condition-independent essential genes. Our computational model-driven analysis provides mechanistic insight into essentiality and contributes novel insights for design of future gene essentiality screens and the identification of core metabolic processes.Author SummaryWith the rise of antibiotic resistance, there is a growing need to discover new therapeutic targets to treat bacterial infections. One attractive strategy is to target genes that are essential for growth and survival. Essential genes can be identified with transposon mutagenesis approaches; however, variability between screens and challenges with interpretation of essentiality data hinder the identification and analysis of essential genes. We performed a large-scale comparison of multiple gene essentiality screens of the microbial pathogen Pseudomonas aeruginosa. We implemented a computational model-driven approach to provide functional explanations for essentiality and reconcile differences between screens. The integration of computational modeling with high-throughput experimental screens may enable the identification of drug targets with high-confidence and provide greater understanding for the development of novel therapeutic strategies.


2014 ◽  
Vol 10 (1) ◽  
pp. 106-133 ◽  
Author(s):  
Lucy Glover ◽  
Sam Alsford ◽  
Nicola Baker ◽  
Daniel J Turner ◽  
Alejandro Sanchez-Flores ◽  
...  

2011 ◽  
Author(s):  
E. Kyzar ◽  
S. Gaikwad ◽  
M. Pham ◽  
J. Green ◽  
A. Roth ◽  
...  

2021 ◽  
Author(s):  
Peng Song ◽  
Jinglu Wang ◽  
Xinyu Guo ◽  
Wanneng Yang ◽  
Chunjiang Zhao

2008 ◽  
Vol 190 (8) ◽  
pp. 2790-2803 ◽  
Author(s):  
Matthew A. Oberhardt ◽  
Jacek Puchałka ◽  
Kimberly E. Fryer ◽  
Vítor A. P. Martins dos Santos ◽  
Jason A. Papin

ABSTRACT Pseudomonas aeruginosa is a major life-threatening opportunistic pathogen that commonly infects immunocompromised patients. This bacterium owes its success as a pathogen largely to its metabolic versatility and flexibility. A thorough understanding of P. aeruginosa's metabolism is thus pivotal for the design of effective intervention strategies. Here we aim to provide, through systems analysis, a basis for the characterization of the genome-scale properties of this pathogen's versatile metabolic network. To this end, we reconstructed a genome-scale metabolic network of Pseudomonas aeruginosa PAO1. This reconstruction accounts for 1,056 genes (19% of the genome), 1,030 proteins, and 883 reactions. Flux balance analysis was used to identify key features of P. aeruginosa metabolism, such as growth yield, under defined conditions and with defined knowledge gaps within the network. BIOLOG substrate oxidation data were used in model expansion, and a genome-scale transposon knockout set was compared against in silico knockout predictions to validate the model. Ultimately, this genome-scale model provides a basic modeling framework with which to explore the metabolism of P. aeruginosa in the context of its environmental and genetic constraints, thereby contributing to a more thorough understanding of the genotype-phenotype relationships in this resourceful and dangerous pathogen.


2021 ◽  
Vol 22 (15) ◽  
pp. 8266
Author(s):  
Minsu Kim ◽  
Chaewon Lee ◽  
Subin Hong ◽  
Song Lim Kim ◽  
Jeong-Ho Baek ◽  
...  

Drought is a main factor limiting crop yields. Modern agricultural technologies such as irrigation systems, ground mulching, and rainwater storage can prevent drought, but these are only temporary solutions. Understanding the physiological, biochemical, and molecular reactions of plants to drought stress is therefore urgent. The recent rapid development of genomics tools has led to an increasing interest in phenomics, i.e., the study of phenotypic plant traits. Among phenomic strategies, high-throughput phenotyping (HTP) is attracting increasing attention as a way to address the bottlenecks of genomic and phenomic studies. HTP provides researchers a non-destructive and non-invasive method yet accurate in analyzing large-scale phenotypic data. This review describes plant responses to drought stress and introduces HTP methods that can detect changes in plant phenotypes in response to drought.


2021 ◽  
Author(s):  
Ecehan Abdik ◽  
Tunahan Cakir

Genome-scale metabolic networks enable systemic investigation of metabolic alterations caused by diseases by providing interpretation of omics data. Although Mus musculus (mouse) is one of the most commonly used model...


Sign in / Sign up

Export Citation Format

Share Document