| 1. |
- Feizi, Amir, 1980, et al.
(författare)
-
Genome-Scale Modeling of the Protein Secretory Machinery in Yeast
- 2013
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 8:5
-
Tidskriftsartikel (refereegranskat)abstract
- The protein secretory machinery in Eukarya is involved in post-translational modification (PTMs) and sorting of the secretory and many transmembrane proteins. While the secretory machinery has been well-studied using classic reductionist approaches, a holistic view of its complex nature is lacking. Here, we present the first genome-scale model for the yeast secretory machinery which captures the knowledge generated through more than 50 years of research. The model is based on the concept of a Protein Specific Information Matrix (PSIM: characterized by seven PTMs features). An algorithm was developed which mimics secretory machinery and assigns each secretory protein to a particular secretory class that determines the set of PTMs and transport steps specific to each protein. Protein abundances were integrated with the model in order to gain system level estimation of the metabolic demands associated with the processing of each specific protein as well as a quantitative estimation of the activity of each component of the secretory machinery.
|
|
| 2. |
- Feizi, Amir, 1980, et al.
(författare)
-
Metabolic and protein interaction sub-networks controlling the proliferation rate of cancer cells and their impact on patient survival
- 2013
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 3
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer cells can have a broad scope of proliferation rates. Here we aim to identify the molecular mechanisms that allow some cancer cell lines to grow up to 4 times faster than other cell lines. The correlation of gene expression profiles with the growth rate in 60 different cell lines has been analyzed using several genome- scale biological networks and new algorithms. New possible regulatory feedback loops have been suggested and the known roles of several cell cycle related transcription factors have been confirmed. Over 100 growth- correlated metabolic sub-networks have been identified, suggesting a key role of simultaneous lipid synthesis and degradation in the energy supply of the cancer cells growth. Many metabolic sub-networks involved in cell line proliferation appeared also to correlate negatively with the survival expectancy of colon cancer patients.
|
|
| 3. |
- Antanaviciute, I., et al.
(författare)
-
Transcriptional hallmarks of cancer cell lines reveal an emerging role of branched chain amino acid catabolism
- 2017
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 7:1, s. Article no 7820 -
-
Tidskriftsartikel (refereegranskat)abstract
- A comparative analysis between cancer cell lines and healthy dividing cells was performed using data (289 microarrays and 50 RNA-seq samples) from 100 different cancer cell lines and 6 types of healthy stem cells. The analysis revealed two large-scale transcriptional events that characterize cancer cell lines. The first event was a large-scale up-regulation pattern associated to epithelial-mesenchymal transition, putatively driven by the interplay of the SP1 transcription factor and the canonical Wnt signaling pathway; the second event was the failure to overexpress a diverse set of genes coding membrane and extracellular proteins. This failure is putatively caused by a lack of activity of the AP-1 complex. It was also shown that the epithelial-mesenchymal transition was associated with the up-regulation of 5 enzymes involved in the degradation of branched chain amino acids. The suitability of silencing one of this enzymes (branched chain amino acid transaminase 2; BCAT2) with therapeutic effects was tested experimentally on the breast cancer cell line MCF-7 and primary cell culture of breast tumor (BCC), leading to lower cell proliferation. The silencing of BCAT2 did not have any significant effect on ASM and MCF10A cells, which were used as models of healthy dividing cells.
|
|
| 4. |
- Borgos, S., et al.
(författare)
-
Mapping global effects of the anti-sigma factor MucA in Pseudomonas fluorescens SBW25 through genome-scale metabolic modeling
- 2013
-
Ingår i: BMC Systems Biology. - : Springer Science and Business Media LLC. - 1752-0509. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundAlginate is an industrially important polysaccharide, currently produced commercially by harvesting of marine brown sea-weeds. The polymer is also synthesized as an exo-polysaccharide by bacteria belonging to the genera Pseudomonas and Azotobacter, and these organisms may represent an alternative alginate source in the future. The current work describes an attempt to rationally develop a biological system tuned for very high levels of alginate production, based on a fundamental understanding of the system through metabolic modeling supported by transcriptomics studies and carefully controlled fermentations.ResultsAlginate biosynthesis in Pseudomonas fluorescens was studied in a genomics perspective, using an alginate over-producing strain carrying a mutation in the anti-sigma factor gene mucA. Cells were cultivated in chemostats under nitrogen limitation on fructose or glycerol as carbon sources, and cell mass, growth rate, sugar uptake, alginate and CO2 production were monitored. In addition a genome scale metabolic model was constructed and samples were collected for transcriptome analyses. The analyses show that polymer production operates in a close to optimal way with respect to stoichiometric utilization of the carbon source and that the cells increase the uptake of carbon source to compensate for the additional needs following from alginate synthesis. The transcriptome studies show that in the presence of the mucA mutation, the alg operon is upregulated together with genes involved in energy generation, genes on both sides of the succinate node of the TCA cycle and genes encoding ribosomal and other translation-related proteins. Strains expressing a functional MucA protein (no alginate production) synthesize cellular biomass in an inefficient way, apparently due to a cycle that involves oxidation of NADPH without ATP production. The results of this study indicate that the most efficient way of using a mucA mutant as a cell factory for alginate production would be to use non-growing conditions and nitrogen deprivation.ConclusionsThe insights gained in this study should be very useful for a future efficient production of microbial alginates.
|
|
| 5. |
- Cvijovic, Marija, 1977, et al.
(författare)
-
Mathematical models of cell factories: moving towards the core of industrial biotechnology
- 2011
-
Ingår i: Microbial Biotechnology. - : Wiley. - 1751-7907 .- 1751-7915. ; 4:5, s. 572-584
-
Tidskriftsartikel (refereegranskat)abstract
- Industrial biotechnology involves the utilization of cell factories for the production of fuels and chemicals. Traditionally, the development of highly productive microbial strains has relied on random mutagenesis and screening. The development of predictive mathematical models provides a new paradigm for the rational design of cell factories. Instead of selecting among a set of strains resulting from random mutagenesis, mathematical models allow the researchers to predict in silico the outcomes of different genetic manipulations and engineer new strains by performing gene deletions or additions leading to a higher productivity of the desired chemicals. In this review we aim to summarize the main modelling approaches of biological processes and illustrate the particular applications that they have found in the field of industrial microbiology.
|
|
| 6. |
- Hernandez, M., et al.
(författare)
-
Modeling of VOC mass transfer in two-liquid phase stirred tank, biotrickling filter and airlift reactors
- 2011
-
Ingår i: Chemical Engineering Journal. - : Elsevier BV. - 1385-8947. ; 172:2-3, s. 961-969
-
Tidskriftsartikel (refereegranskat)abstract
- A modeling framework based on general mass balances and transfer equations was here developed in order to compare the hexane mass transfer performance of two-liquid phase stirred tank reactor (SIR), airlift (ALR) and biotrickling filter (BTF) using silicone oil as model non-aqueous phase under abiotic conditions. This modeling approach resulted in an isomorphous expression for all configurations consisting of a parameter beta*(s) (characterizing the maximum fraction of VOC transferable from the gas to the aqueous phase) and the gradient established between the gas and the aqueous phase. The models were validated against experimental data (at empty bed residence times, EBRT, of 120, 60 and 40 s) exhibiting an overall goodness of fit of 0.98, 0.98 and 0.70 for the two-liquid phase STR, BTF and ALR, respectively. The two-liquid phase BTF exhibited the maximum value of beta*(s) (0.87-0.58), followed by the STR (0.77-0.49) and the ALR (0.23-0.19). Finally, a sensitivity analysis conducted in the two-liquid phase BTF showed that was more sensitive to changes in recirculating liquid flow rate than in the EBRT, confirming that the liquid flow rate is a key operational variable in BTF systems.
|
|
| 7. |
- Hong, Kuk-ki, 1976, et al.
(författare)
-
Dynamic (13) C-labelling experiments prove important differences in protein turnover rate between two Saccharomyces cerevisiae strains
- 2012
-
Ingår i: FEMS Yeast Research. - : Oxford University Press (OUP). - 1567-1356 .- 1567-1364. ; 12:7, s. 741-747
-
Tidskriftsartikel (refereegranskat)abstract
- We developed a method for quantification of protein turnover using (13) C-labelled substrates combined with analysis of the labeling pattern of proteinogenic amino acids. Using this method the specific amino acid turnover rates between proteins and the pool of free amino acids were determined for eight different amino acids (alanine, valine, proline, aspartic acid, glycine, leucine, isoleucine and threonine) in two Saccharomyces cerevisiae strains (CEN.PK 113-7D and YSBN2). Furthermore, proteasome activities were compared for both strains. Both results confirmed the hypothesis of a higher protein turnover rates in CEN.PK 113-7D, which was generated in a previous comparative systems biology study of these two yeast strains. The ATP costs associated with the observed differences in protein turnover were quantified and could explain accurately the differences in biomass yield between both strains that are observed in chemostat cultures. The percent of maintenance ATP associated to protein polymerization (polymerization for growth and re-polymerization due to turnover) and degradation was estimated to be 72% for YSBN2 and 79% for CEN.PK 113-7D, which makes these processes the dominant non-biosynthetic drain of ATP in living cells, and hence it represents an energetic parameter of great relevance.
|
|
| 8. |
- Liu, Liming, 1976, et al.
(författare)
-
Use of genome-scale metabolic models for understanding microbial physiology
- 2010
-
Ingår i: FEBS Letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 584:12, s. 2556-2564
-
Tidskriftsartikel (refereegranskat)abstract
- The exploitation of microorganisms in industrial, medical, food and environmental biotechnology requires a comprehensive understanding of their physiology. The availability of genome sequences and accumulation of high-throughput data allows gaining understanding of microbial physiology at the systems level, and genome-scale metabolic models represent a valuable framework for integrative analysis of metabolism of microorganisms. Genome-scale metabolic models are reconstructed based on a combination of genome sequence information and detailed biochemical information, and these reconstructed models can be used for analyzing and simulating the operation of metabolism in response to different stimuli. Here we discuss the requirement for having detailed physiological insight in order to exploit microorganisms for production of fuels, chemicals and pharmaceuticals. We further describe the reconstruction process of genome-scale metabolic models and different algorithms that can be used to apply these models to gain improved insight into microbial physiology. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
|
|
| 9. |
- Marien, E., et al.
(författare)
-
Non-small cell lung cancer is characterized by dramatic changes in phospholipid profiles
- 2015
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 137:7, s. 1539-1548
-
Tidskriftsartikel (refereegranskat)abstract
- Non-small cell lung cancer (NSCLC) is the leading cause of cancer death globally. To develop better diagnostics and more effective treatments, research in the past decades has focused on identification of molecular changes in the genome, transcriptome, proteome, and more recently also the metabolome. Phospholipids, which nevertheless play a central role in cell functioning, remain poorly explored. Here, using a mass spectrometry (MS)-based phospholipidomics approach, we profiled 179 phospholipid species in malignant and matched non-malignant lung tissue of 162 NSCLC patients (73 in a discovery cohort and 89 in a validation cohort). We identified 91 phospholipid species that were differentially expressed in cancer versus non-malignant tissues. Most prominent changes included a decrease in sphingomyelins (SMs) and an increase in specific phosphatidylinositols (PIs). Also a decrease in multiple phosphatidylserines (PSs) was observed, along with an increase in several phosphatidylethanolamine (PE) and phosphatidylcholine (PC) species, particularly those with 40 or 42 carbon atoms in both fatty acyl chains together. 2D-imaging MS of the most differentially expressed phospholipids confirmed their differential abundance in cancer cells. We identified lipid markers that can discriminate tumor versus normal tissue and different NSCLC subtypes with an AUC (area under the ROC curve) of 0.999 and 0.885, respectively. In conclusion, using both shotgun and 2D-imaging lipidomics analysis, we uncovered a hitherto unrecognized alteration in phospholipid profiles in NSCLC. These changes may have important biological implications and may have significant potential for biomarker development. What's new? Cellular membranes are subject to extensive modification in cancer, often with marked alterations in phospholipid metabolism. The extent and nature of those changes are not fully known, however, particularly for non-small cell lung cancer (NSCLC). In this study, lipidomics analysis of phospholipid profiles uncovered dramatic differences between NSCLC and normal lung tissue. The differences were confirmed via 2D-imaging lipidomics in tissue sections. Lipid markers capable of discriminating between tumor and normal tissue and between different NSCLC subtypes were identified. The observed alterations in NSCLC phospholipid profiles may be biologically significant.
|
|
| 10. |
- Martinez Ruiz, Jose Luis, 1981, et al.
(författare)
-
Gcn4p and the Crabtree effect of yeast: drawing the causal model of the Crabtree effect in Saccharomyces cerevisiae and explaining evolutionary trade-offs of adaptation to galactose through systems biology
- 2014
-
Ingår i: FEMS Yeast Research. - : Oxford University Press (OUP). - 1567-1356 .- 1567-1364. ; 14:4, s. 654-662
-
Tidskriftsartikel (refereegranskat)abstract
- By performing an integrated comparative analysis on the physiology and transcriptome of four different S.cerevisiae strains growing on galactose and glucose, it was inferred that the transcription factors Bas1p, Pho2p, and Gcn4p play a central role in the regulatory events causing the Crabtree effect in S.cerevisiae. The analysis also revealed that a point mutation in the RAS2 observed in a galactose-adapted strain causes a lower Crabtree effect and growth rate on glucose by decreasing the activity of Gcn4p while at the same time is at the origin of higher growth rate on galactose due to a lower activity of the transcriptional repressor Sok2p. The role of Gcn4p on the trade-off effect observed on glucose was confirmed experimentally. This was done by showing that the point mutation in RAS2 does not result in a lower growth rate on glucose if it is introduced in a GCN4-negative background.
|
|
| 11. |
|
|
| 12. |
- Olivares Hernandez, Roberto, 1975, et al.
(författare)
-
Codon usage variability determines the correlation between proteome and transcriptome fold changes
- 2011
-
Ingår i: BMC Systems Biology. - : Springer Science and Business Media LLC. - 1752-0509. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The availability of high throughput experimental methods has made possible to observe the relationships between proteome and transcirptome. The protein abundances show a positive but weak correlation with the concentrations of their cognate mRNAs. This weak correlation implies that there are other crucial effects involved in the regulation of protein translation, different from the sole availability of mRNA. It is well known that ribosome and tRNA concentrations are sources of variation in protein levels. Thus, by using integrated analysis of omics data, genomic information, transcriptome and proteome, we aim to unravel important variables affecting translation. Results: We identified how much of the variability in the correlation between protein and mRNA concentrations can be attributed to the gene codon frequencies. We propose the hypothesis that the influence of codon frequency is due to the competition of cognate and near-cognate tRNA binding; which in turn is a function of the tRNA concentrations. Transcriptome and proteome data were combined in two analytical steps; first, we used Self-Organizing Maps (SOM) to identify similarities among genes, based on their codon frequencies, grouping them into different clusters; and second, we calculated the variance in the protein mRNA correlation in the sampled genes from each cluster. This procedure is justified within a mathematical framework. Conclusions: With the proposed method we observed that in all the six studied cases most of the variability in the relation protein-transcript could be explained by the variation in codon composition.
|
|
| 13. |
- Shoaie, Saeed, 1985, et al.
(författare)
-
Understanding the interactions between bacteria in the human gut through metabolic modeling
- 2013
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 3
-
Tidskriftsartikel (refereegranskat)abstract
- The human gut microbiome plays an influential role in maintaining human health, and it is a potential target for prevention and treatment of disease. Genome-scale metabolic models (GEMs) can provide an increased understanding of the mechanisms behind the effects of diet, the genotype-phenotype relationship and microbial robustness. Here we reconstructed GEMs for three key species, (Bacteroides thetaiotamicron, Eubacterium rectale and Methanobrevibacter smithii) as relevant representatives of three main phyla in the human gut (Bacteroidetes, Firmicutes and Euryarchaeota). We simulated the interactions between these three bacteria in different combinations of gut ecosystems and compared the predictions with the experimental results obtained from colonization of germ free mice. Furthermore, we used our GEMs for analyzing the contribution of each species to the overall metabolism of the gut microbiota based on transcriptome data and demonstrated that these models can be used as a scaffold for understanding bacterial interactions in the gut.
|
|
| 14. |
- Thiele, I., et al.
(författare)
-
A community-driven global reconstruction of human metabolism
- 2013
-
Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 31:5, s. 419-
-
Tidskriftsartikel (refereegranskat)abstract
- Multiple models of human metabolism have been reconstructed, but each represents only a subset of our knowledge. Here we describe Recon 2, a community-driven, consensus 'metabolic reconstruction', which is the most comprehensive representation of human metabolism that is applicable to computational modeling. Compared with its predecessors, the reconstruction has improved topological and functional features, including similar to 2x more reactions and similar to 1.7x more unique metabolites. Using Recon 2 we predicted changes in metabolite biomarkers for 49 inborn errors of metabolism with 77% accuracy when compared to experimental data. Mapping metabolomic data and drug information onto Recon 2 demonstrates its potential for integrating and analyzing diverse data types. Using protein expression data, we automatically generated a compendium of 65 cell type-specific models, providing a basis for manual curation or investigation of cell-specific metabolic properties. Recon 2 will facilitate many future biomedical studies and is freely available at http://humanmetabolism.org/.
|
|
| 15. |
- Velasco, Sergio, 1980
(författare)
-
A metabolic network of a phosphate-accumulating organism provides new insights into enhanced biological phosphorous removal
- 2011
-
Ingår i: Water Science and Technology. - : IWA Publishing. - 0273-1223 .- 1996-9732. ; 64:12, s. 2410-2416
-
Tidskriftsartikel (refereegranskat)abstract
- Here we present a metabolic network representing the central carbon metabolism as well as the synthesis of polyhydroxyalcanohates and the polyphosphate accumulation mechanisms of the bacterium Candidatus Accumulibacter phosphatis, which was previously identified from metagenomic studies in enhanced biological phosphorous removal sludges. The reconstructed metabolic network, together with flux balance analysis can be used to provide new insights into controversial aspects of the metabolism of phosphate-accumulating organisms and is also a tool that can be used in to help enhanced biological phosphorous removal (EBPR) process design and operation.
|
|
| 16. |
- Velasco, Sergio, 1980
(författare)
-
Experimental evidence suggests the existence of evolutionary conserved global operation principles governing microbial metabolism
- 2013
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 3, s. 3017-7
-
Tidskriftsartikel (refereegranskat)abstract
- The search for optimization principles in microbial metabolism, such as biomass or ATP yields or growth rate optimization, has attracted substantial research efforts in the recent years. Here we use the results of C13 labeling experiments together with genome scale metabolic networks of S cerevisiae and E coli in order to assess if there are relationships between systemic variables that are present in both organisms. Strong correlations between the total flux per unit of substrate and the ATP turnover rate per unit of substrate and between the growth rate divided by the total flux and the total flux per unit of substrate were observed for both organisms. We also observed that the common assumption of biomass yield optimization is not consistent with the experiments.
|
|
| 17. |
- Velasco, Sergio, 1980, et al.
(författare)
-
Identification of flux control in metabolic networks using non-equilibrium thermodynamics
- 2010
-
Ingår i: Metabolic Engineering. - : Elsevier BV. - 1096-7176 .- 1096-7184. ; 12:4, s. 369-377
-
Tidskriftsartikel (refereegranskat)abstract
- A method is presented to identify flux controlling reactions in metabolic networks using experimentally determined flux distributions. The method is based on the application of Ziegler's principle for the maximization of entropy production. According to this principle a metabolic network tends to maximize the entropy production rate while satisfying mass balances and maximal rate constraints. Experimental flux data corresponding to four different metabolic states of Saccharomyces cerevisiae were used to identify the corresponding flux controlling reactions. The bottleneck nature of several of the identified reactions was confirmed by earlier studies on over-expression of the identified target genes. The method also explains the failure of all the previous trials of increasing the glycolysis rate by direct over-expression of several glycolytic enzymes. These findings point to a wider use of the method for identification of novel targets for metabolic engineering of microorganisms used for sustainable production of fuels and chemicals.
|
|
| 18. |
- Velasco, Sergio, 1980, et al.
(författare)
-
Mechanistic Model for the Reclamation of Industrial Wastewaters Using Algal-Bacterial Photobioreactors
- 2009
-
Ingår i: Environmental Science & Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 43:9, s. 3200-3207
-
Tidskriftsartikel (refereegranskat)abstract
- A mechanistic model describing the steady-state biodegradation of inhibitory pollutants by algal-bacterial consortia in enclosed chemostat photobioreactors; was developed. The model was then validated against experimental data on salicylate removal by a Chlorella Sorokiniana/Ralstonia basilensis consortium cultivated without external O-2 supplied in an enclosed chemostat photobioreactor under various conditions of photon flux radiation, salicylate inlet concentrations, temperatures, and hydraulic retention times (HRT). A satisfactory fit of experimental data was achieved in both the fitting and validation data sets (11% of average relative error). The model was thus capable of describing satisfactorily the influence of the HRT and the combined increase of light input and temperature on salicylate removal efficiency (RE). The potential inhibitory effect of salicylate was considered into the model structure based on the influence of salicylate concentration on microalgae photosynthetic activity. Only four adjustable parameters were necessary when using this modeling approach,which significantly reduces the number of experimental kinetic and stoichiometric coefficients needed for process description. Variables such as reactor geometry and light absorption characteristics of the biomass were grouped into a single parameter, which highly simplifies photobioreactor modeling. Being based on stoichiometric, thermodynamic, and mass balances analysis, this model can be extended to the removal of any organic pollutant in industrial wastewaters and to any photobioreactor configuration. It therefore provides an important tool to assess the feasibility of pollutant biodegradation under full photosynthetic oxygenation (i.e., no external O-2 supply) and to optimize photobioreactors by establishing the conditions under which complete pollutant removal can be achieved. The model herein developed also provides a tool to better understand the complex relationships between microalgae, bacteria, light, and pollutant concentration, which will promote the development of algal-bacterial processes as a cost-effective alternative for wastewater reclamation and algae production from wastewater.
|
|
| 19. |
- Velasco, Sergio, 1980, et al.
(författare)
-
Modelling gas-liquid VOCs transport in two-liquid phase partitioning bioreactors
- 2010
-
Ingår i: International Journal of Heat and Mass Transfer. - : Elsevier BV. - 0017-9310. ; 53:5-6, s. 1139-1145
-
Tidskriftsartikel (refereegranskat)abstract
- A mechanistic model capable to accurately describe the mass transport of hexane in a two-liquid phase partitioning bioreactor (TLPB) constructed with silicone oil was developed. This work constitutes the first step in the development of simple and reliable models for the mathematical description of the off-gas treatment of volatile organic contaminants in TLPBs. The model (based oil general mass balances and transport equations over off-gas rising bubbles) predicted a negative linear relationship between the fraction of organic phase and the logarithm of the pollutant fraction that remains in the gas phase The average relative errors of the model predictions were lower than 7%. Under the tested range of operational conditions (organic phase fractions and stirring rates ranging from 5% to 30% and from 100 to 300 rprn, respectively) the Maximum hexane fraction transferred from the gas to the liquid (aqueous + organic) phase increased at increasing stirring rates and silicone oil fractions up to 200 rprn and 20%, respectively. In addition, the proposed modelling approach quantified the proximity of the dispersion to thermodynamic equilibrium conditions. predicting thus the degree of mixing in the systems.
|
|
| 20. |
- Velasco, Sergio, 1980
(författare)
-
Non-equilibrium statistical mechanics: partition functions and steepest entropy increase
- 2011
-
Ingår i: Journal of Statistical Mechanics: Theory and Experiment. - : IOP Publishing. - 1742-5468. ; 2011:5
-
Tidskriftsartikel (refereegranskat)abstract
- On the basis of just the microscopic definition of thermodynamic entropy and the definition of the rate of entropy increase as the sum of products of thermodynamic fluxes and their conjugated forces, we have derived a general expression for non-equilibrium partition functions, which has the same form as the partition function previously obtained by other authors using different assumptions. Secondly we show that Onsager's reciprocity relations are equivalent to the assumption of steepest entropy ascent, independently of the choice of metric for the space of probability distributions. Finally we show that the Fisher-Rao metric for the space of probability distributions is the only one that guarantees that dissipative systems are what we call constantly describable (describable in terms of the same set of macroscopic observables during their entire trajectory of evolution towards equilibrium). The Fisher-Rao metric is fundamental to Beretta's dissipative quantum mechanics; therefore our last result provides a further justification for Beretta's theory.
|
|
| 21. |
- Velasco, Sergio, 1980, et al.
(författare)
-
Random sampling of metabolic networks
- 2009
-
Ingår i: New Biotechnology. - : Elsevier BV. - 1876-4347 .- 1871-6784. ; 25:Suppl. 1 Published: SEP 2009 ; Meeting abstract, s. S336-S336
-
Tidskriftsartikel (refereegranskat)
|
|
| 22. |
- Velasco, Sergio, 1980, et al.
(författare)
-
Sampling the Solution Space in Genome-Scale Metabolic Networks Reveals Transcriptional Regulation in Key Enzymes
- 2010
-
Ingår i: PLoS Computational Biology. - : Public Library of Science (PLoS). - 1553-734X .- 1553-7358. ; 6:7, s. 16-16
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-scale metabolic models are available for an increasing number of organisms and can be used to define the region of feasible metabolic flux distributions. In this work we use as constraints a small set of experimental metabolic fluxes, which reduces the region of feasible metabolic states. Once the region of feasible flux distributions has been defined, a set of possible flux distributions is obtained by random sampling and the averages and standard deviations for each of the metabolic fluxes in the genome-scale model are calculated. These values allow estimation of the significance of change for each reaction rate between different conditions and comparison of it with the significance of change in gene transcription for the corresponding enzymes. The comparison of flux change and gene expression allows identification of enzymes showing a significant correlation between flux change and expression change (transcriptional regulation) as well as reactions whose flux change is likely to be driven only by changes in the metabolite concentrations (metabolic regulation). The changes due to growth on four different carbon sources and as a consequence of five gene deletions were analyzed for Saccharomyces cerevisiae. The enzymes with transcriptional regulation showed enrichment in certain transcription factors. This has not been previously reported. The information provided by the presented method could guide the discovery of new metabolic engineering strategies or the identification of drug targets for treatment of metabolic diseases.
|
|
| 23. |
- Velasco, Sergio, 1980
(författare)
-
Steepest entropy increase is justified by information theory. The relations between Ziegler's principle, Onsager's formalism and Prigogine's principle
- 2010
-
Ingår i: Physica A: Statistical Mechanics and its Applications. - : Elsevier BV. - 0378-4371. ; 389:21, s. 4564-4570
-
Tidskriftsartikel (refereegranskat)abstract
- Evidence for Ziegler's principle of maximum entropy production has been accumulated from different fields such as climatic studies, crystal growth, dynamics of ecosystems and cellular metabolism. However, Ziegler's principle is still seen with scepticism by the scientific community. The reasons for this scepticism are the absence of an accepted theoretical justification as well as the fact that Ziegler's principle formulation seems to contradict Prigogine's principle of minimum entropy production. In this work we aim to provide a theoretical justification for Ziegler's principle based on information theory, which is at the basis of Gibbs' formalism for statistical physics. Similar approaches have previously been attempted, however we believe that the justification provided here is simpler and relies in less questionable hypotheses. Once Ziegler's principle has been formulated as a consequence of information theory, its relations with Onsager's formulation and Prigogine's principle are explored. (C) 2010 Elsevier BM. All rights reserved.
|
|
| 24. |
- Velasco, Sergio, 1980
(författare)
-
Symmetries and nonequilibrium thermodynamics
- 2017
-
Ingår i: Physical Review E. - 2470-0045 .- 2470-0053. ; 95:6
-
Tidskriftsartikel (refereegranskat)abstract
- Thermodynamic systems can be defined as composed by many identical interacting subsystems. Here it is shown how the dynamics of relaxation toward equilibrium of a thermodynamic system is closely related to the symmetry group of the Hamiltonian of the subsystems of which it is composed. The transitions between states driven by the interactions between identical subsystems correspond to elements of the root system associated to the symmetry group of their Hamiltonian. This imposes constraints on the relaxation dynamics of the complete thermodynamic system, which allow formulating its evolution toward equilibrium as a system of linear differential equations in which the variables are the thermodynamic forces of the system. The trajectory of a thermodynamic system in the space of thermodynamic forces corresponds to the negative gradient of a potential function, which depends on the symmetry group of the Hamiltonian of the individual interacting subsystems.
|
|
| 25. |
- Ågren, Rasmus, 1982, et al.
(författare)
-
Reconstruction of Genome-Scale Active Metabolic Networks for 69 Human Cell Types and 16 Cancer Types Using INIT
- 2012
-
Ingår i: PLoS Computational Biology. - : Public Library of Science (PLoS). - 1553-734X .- 1553-7358. ; 8:5
-
Tidskriftsartikel (refereegranskat)abstract
- Development of high throughput analytical methods has given physicians the potential access to extensive and patient-specific data sets, such as gene sequences, gene expression profiles or metabolite footprints. This opens for a new approach in health care, which is both personalized and based on system-level analysis. Genome-scale metabolic networks provide a mechanistic description of the relationships between different genes, which is valuable for the analysis and interpretation of large experimental data-sets. Here we describe the generation of genome-scale active metabolic networks for 69 different cell types and 16 cancer types using the INIT (Integrative Network Inference for Tissues) algorithm. The INIT algorithm uses cell type specific information about protein abundances contained in the Human Proteome Atlas as the main source of evidence. The generated models constitute the first step towards establishing a Human Metabolic Atlas, which will be a comprehensive description (accessible online) of the metabolism of different human cell types, and will allow for tissue-level and organism-level simulations in order to achieve a better understanding of complex diseases. A comparative analysis between the active metabolic networks of cancer types and healthy cell types allowed for identification of cancer-specific metabolic features that constitute generic potential drug targets for cancer treatment.
|
|
| 26. |
- Österlund, Tobias, 1984, et al.
(författare)
-
Controllability analysis of transcriptional regulatory networks reveals circular control patterns among transcription factors
- 2015
-
Ingår i: Integrative Biology (United Kingdom). - : Oxford University Press (OUP). - 1757-9694 .- 1757-9708. ; 7:5, s. 560-568
-
Tidskriftsartikel (refereegranskat)abstract
- Transcriptional regulation is the most committed type of regulation in living cells where transcription factors (TFs) control the expression of their target genes and TF expression is controlled by other TFs forming complex transcriptional regulatory networks that can be highly interconnected. Here we analyze the topology and organization of nine transcriptional regulatory networks for E. coli, yeast, mouse and human, and we evaluate how the structure of these networks influences two of their key properties, namely controllability and stability. We calculate the controllability for each network as a measure of the organization and interconnectivity of the network. We find that the number of driver nodes n(D) needed to control the whole network is 64% of the TFs in the E. coli transcriptional regulatory network in contrast to only 17% for the yeast network, 4% for the mouse network and 8% for the human network. The high controllability (low number of drivers needed to control the system) in yeast, mouse and human is due to the presence of internal loops in their regulatory networks where the TFs regulate each other in a circular fashion. We refer to these internal loops as circular control motifs (CCM). The E. coli transcriptional regulatory network, which does not have any CCMs, shows a hierarchical structure of the transcriptional regulatory network in contrast to the eukaryal networks. The presence of CCMs also has influence on the stability of these networks, as the presence of cycles can be associated with potential unstable steady-states where even small changes in binding affinities can cause dramatic rearrangements of the state of the network.
|
|
| 27. |
- Österlund, Tobias, 1984, et al.
(författare)
-
Mapping condition-dependent regulation of metabolism in yeast through genome-scale modeling
- 2013
-
Ingår i: BMC Systems Biology. - : Springer Science and Business Media LLC. - 1752-0509. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Background:The genome-scale metabolic model of Saccharomyces cerevisiae, first presented in 2003, was the first genome-scale network reconstruction for a eukaryotic organism. Since then continuous efforts have been made in order to improve and expand the yeast metabolic network.Results:Here we present iTO977, a comprehensive genome-scale metabolic model that contains more reactions, metabolites and genes than previous models. The model was constructed based on two earlier reconstructions, namely iIN800 and the consensus network, and then improved and expanded using gap-filling methods and by introducing new reactions and pathways based on studies of the literature and databases. The model was shown to perform well both for growth simulations in different media and gene essentiality analysis for single and double knock-outs. Further, the model was used as a scaffold for integrating transcriptomics, and flux data from four different conditions in order to identify transcriptionally controlled reactions, i.e. reactions that change both in flux and transcription between the compared conditions.Conclusion:We present a new yeast model that represents a comprehensive up-to-date collection of knowledge on yeast metabolism. The model was used for simulating the yeast metabolism under four different growth conditions and experimental data from these four conditions was integrated to the model. The model together with experimental data is a useful tool to identify condition-dependent changes of metabolism between different environmental conditions.
|
|
