Genome-scale analysis to the impact of gene deletion on the metabolism of E. coli: constraint-based simulation approach

Abstract

Background: Genome-scale models of metabolism have only been analyzed with the constraint-based modelling philosophy. Some gene deletion studies on in silico organism models at genome-scale have been made, but most of them were from the aspects of distinguishing lethal and non-lethal genes or growth rate. The impact of gene deletion on flux redistribution, the functions and characters of key genes, and the performance of different reactions in entire gene deletion still lack research.

Results: Three main researches have been done into the metabolism of E. coli in gene deletion. The first work was about finding key genes and subsystems: First, by calculating the deletion impact p of whole 1261 genes, one by one, on the metabolic flux redistribution of E. coli_iAF1260, we can find that p is more detailed in describing the change of organism's metabolism. Next, we sought out 195 important (high-p) genes, and they are more than essential genes (growth rate f becomes zero if deleting). So we speculated that under some circumstances and when an important gene is deleted, a big change in the metabolic system of E. coli has taken place and E. coli may use other reaction ways to strive to live. Further, by determining the functional subsystems to which 195 key genes belong, we found that their distribution to subsystems was not even and most of them were related to just three subsystems and that all of the 8 important but not essential genes appear just in "Oxidative Phosphorylation". Our second work was about p's three characters: We analyzed the correlation between p and d (connection degree of one gene) and the correlation between p and vgene (flux sum controlled by one gene), and found that both of them are not of linear correlation, but the correlation between p and f is of highly linear correlation. The third work was about highly-affected reactions: We found 16 reactions with more than 2000 Rg value (measuring the impact that a reaction is gotten in the whole 1261 gene deletion). We speculated that highly-affected reactions involve in the metabolism of basic biomasses.

Conclusion: To sum up, these results we obtained have biological significances and our researches will shed new light on the future researches.

Figure 1

Flux distribution of E. coli_iAF1260. X-axis indicating every reaction in rxns (the order is as the same as in rxns, total 2382) and y-axis indicating the value of its corresponding flux (unit is mmol gDW^-1h^-1). Rxns is the reaction set in the model.

Figure 2

The deletion impact p of 1261 genes of the E. coli_iAF1260 model. X-axis indicating every gene in 1261 genes (the order is as the same as in genes, total 1261) and y-axis indicating its impact p. Genes is the set of genes in model.

Figure 3

The deletion impact of 1261 genes to f of the E. coli_iAF1260 model. X-axis indicating every gene in 1261 genes and y-axis indicating new f after its deletion.

Figure 4

The scatter diagram (p, f). X-axis indicating p and y-axis indicating f, total 1261 data pairs. Many data pairs locate at the same points.

Figure 5

The related reaction number of every gene in 1261 genes of the E. coli_iAF1260 model. X-axis indicating every gene in 1261 genes (the order is as the same as in genes, total 1261) and y-axis indicating the number of its related reactions.

Figure 6

The scatter diagram (d, p). X-axis indicating d (connection degree of every gene) and y-axis indicating the corresponding gene impact p.

Figure 7

The controlled reaction number of every gene in 1261 genes of the E. coli_iAF1260 model. X-axis indicating every gene in 1261 genes (the order is as the same as in genes, total 1261) and y-axis indicating the number of its controlled reactions.

Figure 8

The scatter diagram (v_gene, p). X-axis indicating v_gene (the flux sum controlled by every gene) and y-axis indicating the impact, p.

Figure 9

The Rg of each 2382 reactions of E. coli_iAF1260. X-axis indicating every reaction in 2382 reactions (the order is as the same as in rxns, total 2382) and y-axis indicating its corresponding Rg value.