Gene Deletion Analysis

General concept

Metabolic gene essentiality can be predicted in a constraint based model by blocking all reactions that depend upon a gene of interest. If the gene is essential, its removal will decrease the in silico fitness (e.g., the model will predict no growth). With the first genome-scale metabolic reconstruction, all single and double gene deletion mutants were simulated to assesses the essentiality of each gene. (1)

Items to consider when implementing

Gene deletion analysis requires the use of known gene-protein-reaction association. However, reaction deletion analysis is also frequently used by removing reactions without addressing gene-reaction associations. Such analyses should be assessed with care.

Software packages with this method

Applications of interest

Edwards and Palsson (2000). Metabolic gene essentiality was predicted using the first genome-scale reconstruction of E. coli metabolism. The authors sequentially removed each gene to test if in silico growth can still be attained. In this analysis, it was found that ~86% of verified in silico predictions were consistent with experimentally assessed gene essentiality.

Badarinarayana, et al. (2001) used FBA to study a number of gene disruption mutants generated using a transposon insertion library. The distribution of mutants were assessed using DNA microarrays.

Rodrigues and Wagner (2009) randomly added and deleted reactions to study the plasticity of metabolic networks through evolution.

Wang and Zhang (2011) used reaction deletion to study the effects of gene expression noise on fitness.

Ho Sui, et al. (2012) used gene deletion analysis in a drug repurposing screen. Through this, an osteoporosis drug was predicted to have antimicrobial capacity. Through several in vitro and in vivo tests the compound was found to act as an antibiotic against Pseudomonas aeruginosa.

Relevant references

Edwards JS, Palsson BO. Systems properties of the Haemophilus influenzae Rd metabolic genotype. J Biol Chem. 1999 Jun 18;274(25):17410-6.

Edwards JS, Palsson BO. The Escherichia coli MG1655 in silico metabolic genotype: its definition, characteristics, and capabilities. Proc Natl Acad Sci U S A. 2000 May 9;97(10):5hi528-33.

Related methods

MOMA

ROOM

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