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An expanded genome-scale metabolic model of E. coli (iJR904 GSM/GPR) has been reconstructed which includes 904 genes and 931 unique biochemical reactions. The reactions in the expanded model are both elementally and charge balanced. Network gap analysis led to putative assignments for 55 open reading frames (ORFs). Gene to protein to reaction associations (GPR) are now directly included in the model. Comparisons between predictions made by iJR904 and iJE660a models show that they are generally similar but differ under certain circumstances. Analysis of genome-scale proton balancing shows how the flux of protons into and out of the medium is important for maximizing cellular growth.
The constraint-based modeling approach has been used to study E. coli metabolism for over ten years; the history of such model building efforts has recently been reviewed [7]. The first genome-scale metabolic (GSM) model accounting for 660 gene products (iJE660 GSM) was reconstructed using genomic information, biochemical data and physiological data [8]. This genome-scale model has been used to perform in silico gene deletion studies [8] and to predict both optimal growth behavior [9] and the outcome of adaptive evolution [10].
This paper reports an expansion of iJE660a GSM, which itself is a slight modification of the original genome-scale metabolic model (iJE660 GSM) [8]. Gene to protein to reaction (GPR) associations are included directly in the new model (iJR904 GSM/GPR). These associations describe the dependence of reactions on proteins and proteins on genes (Figure 2). The metabolic network described by iJR904 has also changed; individual reactions are now elementally and charge balanced, and a significant number of new genes and novel reactions have been added to the model. iJR904 GSM/GPR accounts for over 904 genes and the 931 unique biochemical reactions the encoded proteins carry out. This paper discusses the effects that these additional reactions have on the predictive capabilities of the model and identifies putative ORFs in the genome which could resolve gaps in the metabolic network.
Since computational models of E. coli will continue to grow in size and scope [7] it will become important to be able to distinguish between the different models - a naming convention will aid in this effort. The naming convention we chose to use mirrors the one already established for plasmids. The general form of the names of in silico strains used is iXXxxxa YYY. The 'i' in the name refers to an in silico model (that is, a computer model). This 'i' is followed by the initials (XX) of the person who developed the model and then the number of genes (xxx) included in the model. Any letters (a) after the number of genes indicates that slight modifications were made to the model, for instance iJE660a is derived from iJE660. Further designation of the content and scope of a model are found in YYY; here the acronyms GSM and GPR stand for genome-scale model and gene-protein-reaction associations, respectively. The contents of iJE660a and iJR904 can be found on our website [11], and iJR904 is also detailed in the additional data files.
The metabolic network described by E. coli iJE660a has expanded in size from 627 unique reactions and 438 metabolites to 931 unique reactions and 625 metabolites in iJR904. Complete maps containing all the reactions in the metabolic network are available in the additional data files and can also be downloaded from [11]. The molecular formulae and charges for the metabolites in the model were determined assuming a pH of 7.2. Fifty-eight of the reactions in iJR904 currently do not have associated genes. A complete list of the reactions can be found in the additional data files. Putative functional gene assignments account for 23 of the added reactions, with the majority of these being putative transporters.
This paper reports the curation and expansion of a previous genome-scale constraint-based model of E. coli metabolism (iJE660a GSM) that is now used in multiple laboratories (A.L. Barabasi, personal communication; Church and colleagues [23]; H. Greenberg, personal communication and C. Maranas, personal communication). This expanded model, iJR904 GSM/GPR, includes 37% more metabolic genes and 47% more metabolic reactions. Each reaction in the network is now both elementally and charge balanced with the exception of the six reactions listed in Table 1. While the new reactions added to the network do not change many of the predicted optimal phenotypes, there are instances in which the expanded model makes significantly different predictions, examples of which occur when glycerol, glucose, malate, acetate and αKG are used as the carbon sources under oxygen-limited conditions.
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Explanation: This criterion influences external validity, but not the internal or statistical validity of the trial. It has been included in the PEDro scale so that all items of the Delphi scale are represented on the PEDro scale. This item is not used to calculate the PEDro score.
The Spanish versions of the long (26-item) and short (12-item) forms of the SCS are valid and reliable instruments for the evaluation of self-compassion among the general population. These results substantiate the use of this scale in research and clinical practice.
Self-compassion is assessed using the Self-Compassion Scale [10]. The original SCS contains 26 items, measuring six components of self-compassion: Self-Kindness, Self-Judgment, Common Humanity, Isolation, Mindfulness and Over-Identification [10]. Adequate psycho