Systems biology definition of the core proteome of metabolism and expression is consistent with high-throughput data

Abstract

Finding the minimal set of gene functions needed to sustain life is of both fundamental and practical importance. Minimal gene lists have been proposed by using comparative genomics-based core proteome definitions. A definition of a core proteome that is supported by empirical data, is understood at the systems-level, and provides a basis for computing essential cell functions is lacking. Here, we use a systems biology-based genome-scale model of metabolism and expression to define a functional core proteome consisting of 356 gene products, accounting for 44% of the Escherichia coli proteome by mass based on proteomics data. This systems biology core proteome includes 212 genes not found in previous comparative genomics-based core proteome definitions, accounts for 65% of known essential genes in E. coli, and has 78% gene function overlap with minimal genomes (Buchnera aphidicola and Mycoplasma genitalium). Based on transcriptomics data across environmental and genetic backgrounds, the systems biology core proteome is significantly enriched in nondifferentially expressed genes and depleted in differentially expressed genes. Compared with the noncore, core gene expression levels are also similar across genetic backgrounds (two times higher Spearman rank correlation) and exhibit significantly more complex transcriptional and posttranscriptional regulatory features (40% more transcription start sites per gene, 22% longer 5′UTR). Thus, genome-scale systems biology approaches rigorously identify a functional core proteome needed to support growth. This framework, validated by using high-throughput datasets, facilitates a mechanistic understanding of systems-level core proteome function through in silico models; it de facto defines a paleome.

Deciphering global gene expression and regulation strategy in Escherichia coli during carbon limitation

“…Interestingly, among the top 100 genes, 49 and 43 genes (respectively in the 0.9 h −1 and the 0.2 h −1 transcriptome) were also genes deemed essential (Baba et al ., ), substantiating previous work that showed that essential genes, which make the major component of the core proteome (Yang et al ., ), tend to be highly expressed (Acevedo‐Rocha et al ., ). Indeed, we found that the expression level of all genes recognized as essential was significantly higher than that of the non‐essential genes (Fig.…”

Comparative proteomic analysis of four biotechnological strains Lactococcus lactis through label‐free quantitative proteomics

“…Systems biological approaches are based in the broad range of large-scale data collection, these dataset obtained from 'omics' approaches associated with computational tool has promote insights in the dynamic behaviour of a system (Voit et al, 2006;Yang et al, 2015). In this present study, we combined genomic dataset, high-throughput proteomic and PPI network analysis for characterized the L. lactis proteome, which we enabled create a link between genotype and phenotype this bacteria.…”

“…Despite all proteomic studies, currently, no work was conducted to characterize the L. lactis core proteome. Studies show that the knowledge of a core functional proteome is important extremely for both developing fundamental understanding of cell functions and for synthetic biology applications (Zhang et al, 2014;Yang et al, 2015). So to better insights about factors related to the physiologic process of L. lactis and to complement previous studies related to both structural and functional genome of this bacterium.…”

EumicrobeDBLite: a lightweight genomic resource and analytic platform for draft oomycete genomes

“…Cluster information and the tree structure for a protein are also available on the protein's gene detail page. A pre-computed cluster analysis for core orthologues is a very valuable resource for inferring the biological role and phylogeny of a protein sequence (Yang et al, 2015).…”