METABOLIC NETWORKS ROBUSTNESS: THEORY, SIMULATIONS AND RESULTS

2011 ◽  
Vol 12 (03) ◽  
pp. 221-240 ◽  
Author(s):  
SALVATORE VITABILE ◽  
VINCENZO CONTI ◽  
BARBARA LANZA ◽  
DOMENICO CUSUMANO ◽  
FLIPPO SORBELLO

Metabolic networks are composed of several functional modules, reproducing metabolic pathways and describing the entire cellular metabolism of an organism. In the last decade, an enormous interest has grown for the study of tolerance to errors and attacks in metabolic networks. Studies on their robustness have suggested that metabolic networks are tolerant to errors, but very vulnerable to targeted attacks against highly connected nodes. However, many findings on metabolic networks suggest that the above classification is too simple and imprecise, since hub node attacks can be by-passed if alternative metabolic paths can be exploited. On the contrary, non-hub nodes attacks can affect cell survival when the node is the only path within a functional module. In this paper an integrated approach for metabolic networks robustness analysis is presented. With more details, statistical, topological, and functional analysis are used together to evaluate metabolic network behavior under normal operation conditions and under random or targeted attacks. Two real biological metabolic networks have been used to test the effectiveness of the proposed approach.

Author(s):  
Ryan M Patrick ◽  
Xing-Qi Huang ◽  
Natalia Dudareva ◽  
Ying Li

Abstract Biosynthesis of secondary metabolites relies on primary metabolic pathways to provide precursors, energy, and cofactors, thus requiring coordinated regulation of primary and secondary metabolic networks. However, to date, it remains largely unknown how this coordination is achieved. Using Petunia hybrida flowers, which emit high levels of phenylpropanoid/benzenoid volatile organic compounds (VOCs), we uncovered genome-wide dynamic deposition of histone H3 lysine 9 acetylation (H3K9ac) during anthesis as an underlying mechanism to coordinate primary and secondary metabolic networks. The observed epigenome reprogramming is accompanied by transcriptional activation at gene loci involved in primary metabolic pathways that provide precursor phenylalanine, as well as secondary metabolic pathways to produce volatile compounds. We also observed transcriptional repression among genes involved in alternative phenylpropanoid branches that compete for metabolic precursors. We show that GNAT family histone acetyltransferase(s) (HATs) are required for the expression of genes involved in VOC biosynthesis and emission, by using chemical inhibitors of HATs, and by knocking down a specific HAT gene, ELP3, through transient RNAi. Together, our study supports that regulatory mechanisms at chromatin level may play an essential role in activating primary and secondary metabolic pathways to regulate VOC synthesis in petunia flowers.


Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2634
Author(s):  
Beatriz Soldevilla ◽  
Angeles López-López ◽  
Alberto Lens-Pardo ◽  
Carlos Carretero-Puche ◽  
Angeles Lopez-Gonzalvez ◽  
...  

Purpose: High-throughput “-omic” technologies have enabled the detailed analysis of metabolic networks in several cancers, but NETs have not been explored to date. We aim to assess the metabolomic profile of NET patients to understand metabolic deregulation in these tumors and identify novel biomarkers with clinical potential. Methods: Plasma samples from 77 NETs and 68 controls were profiled by GC−MS, CE−MS and LC−MS untargeted metabolomics. OPLS-DA was performed to evaluate metabolomic differences. Related pathways were explored using Metaboanalyst 4.0. Finally, ROC and OPLS-DA analyses were performed to select metabolites with biomarker potential. Results: We identified 155 differential compounds between NETs and controls. We have detected an increase of bile acids, sugars, oxidized lipids and oxidized products from arachidonic acid and a decrease of carnitine levels in NETs. MPA/MSEA identified 32 enriched metabolic pathways in NETs related with the TCA cycle and amino acid metabolism. Finally, OPLS-DA and ROC analysis revealed 48 metabolites with diagnostic potential. Conclusions: This study provides, for the first time, a comprehensive metabolic profile of NET patients and identifies a distinctive metabolic signature in plasma of potential clinical use. A reduced set of metabolites of high diagnostic accuracy has been identified. Additionally, new enriched metabolic pathways annotated may open innovative avenues of clinical research.


Metabolites ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 66 ◽  
Author(s):  
Manu Shree ◽  
Shyam K. Masakapalli

The goal of this study is to map the metabolic pathways of poorly understood bacterial phytopathogen, Xanthomonas oryzae (Xoo) BXO43 fed with plant mimicking media XOM2 containing glutamate, methionine and either 40% [13C5] xylose or 40% [13C6] glucose. The metabolic networks mapped using the KEGG mapper and the mass isotopomer fragments of proteinogenic amino acids derived from GC-MS provided insights into the activities of Xoo central metabolic pathways. The average 13C in histidine, aspartate and other amino acids confirmed the activities of PPP, the TCA cycle and amino acid biosynthetic routes, respectively. The similar labelling patterns of amino acids (His, Ala, Ser, Val and Gly) from glucose and xylose feeding experiments suggests that PPP would be the main metabolic route in Xoo. Owing to the lack of annotated gene phosphoglucoisomerase in BXO43, the 13C incorporation in alanine could not be attributed to the competing pathways and hence warrants additional positional labelling experiments. The negligible presence of 13C incorporation in methionine brings into question its potential role in metabolism and pathogenicity. The extent of the average 13C labelling in several amino acids highlighted the contribution of pre-existing pools that need to be accounted for in 13C-flux analysis studies. This study provided the first qualitative insights into central carbon metabolic pathway activities in Xoo.


2019 ◽  
Vol 7 (3A) ◽  
Author(s):  
Claubia Pereira ◽  
Jéssica P. Achilles ◽  
Fabiano Cardoso ◽  
Victor F. Castro ◽  
Maria Auxiliadora F. Veloso

A spent fuel pool of a typical Pressurized Water Reactor (PWR) was evaluated for criticality studies when it uses reprocessed fuels. PWR nuclear fuel assemblies with four types of fuels were considered: standard PWR fuel, MOX fuel, thorium-uranium fuel and reprocessed transuranic fuel spiked with thorium. The MOX and UO2 benchmark model was evaluated using SCALE 6.0 code with KENO-V transport code and then, adopted as a reference for other fuels compositions. The four fuel assemblies were submitted to irradiation at normal operation conditions. The burnup calculations were obtained using the TRITON sequence in the SCALE 6.0 code package. The fuel assemblies modeled use a benchmark 17x17 PWR fuel assembly dimensions. After irradiation, the fuels were inserted in the pool. The criticality safety limits were performed using the KENO-V transport code in the CSAS5 sequence. It was shown that mixing a quarter of reprocessed fuel withUO2 fuel in the pool, it would not need to be resized 


2020 ◽  
Author(s):  
Tom J. Clement ◽  
Erik B. Baalhuis ◽  
Bas Teusink ◽  
Frank J. Bruggeman ◽  
Robert Planqué ◽  
...  

AbstractThe metabolic capabilities of cells determine their biotechnological potential, fitness in ecosystems, pathogenic threat levels, and function in multicellular organisms. Their comprehensive experimental characterisation is generally not feasible, particularly for unculturable organisms. In principle, the full range of metabolic capabilities can be computed from an organism’s annotated genome using metabolic network reconstruction. However, current computational methods cannot deal with genome-scale metabolic networks. Part of the problem is that these methods aim to enumerate all metabolic pathways, while computation of all (elementally balanced) conversions between nutrients and products would suffice. Indeed, the elementary conversion modes (ECMs, defined by Urbanczik and Wagner) capture the full metabolic capabilities of a network, but the use of ECMs has not been accessible, until now. We extend and explain the theory of ECMs, implement their enumeration in ecmtool, and illustrate their applicability. This work contributes to the elucidation of the full metabolic footprint of any cell.


2020 ◽  
pp. 34-42
Author(s):  
Liudmyla Kryvoplias-Volodina ◽  
Oleksandr Gavva ◽  
Anastasiia Derenivska ◽  
Oleksandr Volodin

The complex of technical means for optimization synthesis of assembling of a packing machine of separate functional modules has been developed. The method of synthesis of a packing machine, based on criterial assessment of separate functional modules (FM), combined by two main assessment groups, has been offered. FM may be selected and calculated by the program of consumption, based on the overall equipment effectiveness (OEE) criterion. An example of synthesis, based on the offered method, takes into account variants of choice of ready functional modules, based on the hierarchic structure of a module of roll packing material supply. The method takes into account the systemic approach to analysis of equipment constructions for packing fine-piece and piece food products in a consumption package. The synthesis of FM assembling as conceptual models, abstract ones, reflecting the construction structure and connections between separate elements – functional devices (FD) – has been offered. The optimal assembling of the functional device in the structure of the functional module of roll packing material supply has been determined. As a result of solving this problem, a FM1 prototype has been created. At conducting the comparative analysis with the existent equipment, the automatic functional device has been modeled. The use of the OEE criterion with joint properties that reflects the generalized assessment of a packing machine or functional module with a maximin (minimax) criterion by the compromise principle has been substantiated. The analysis is grounded on the idea of optimality of each module or device of the machine for packing food products at adding each next functional module to its composition. The program of assessment calculation of the package equipment with the complex assessment criterion OEE for different assembling of FMi machines for packing piece and fine-piece products has been developed. The FM of roll film material supply with using a microprocessor managing device that maintains a sinusoidal law of movement of a stretching roll of the packing machine has been developed. Optimal characteristics of the technical system have been determined. Results, obtained at processing experimental data, confirm adequacy of the offered method for assessing assembling solutions


2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
A. Romero ◽  
Y. Lage ◽  
S. Soua ◽  
B. Wang ◽  
T.-H. Gan

Reliable monitoring for the early fault diagnosis of gearbox faults is of great concern for the wind industry. This paper presents a novel approach for health condition monitoring (CM) and fault diagnosis in wind turbine gearboxes using vibration analysis. This methodology is based on a machine learning algorithm that generates a baseline for the identification of deviations from the normal operation conditions of the turbine and the intrinsic characteristic-scale decomposition (ICD) method for fault type recognition. Outliers picked up during the baseline stage are decomposed by the ICD method to obtain the product components which reveal the fault information. The new methodology proposed for gear and bearing defect identification was validated by laboratory and field trials, comparing well with the methods reviewed in the literature.


2018 ◽  
Vol 9 ◽  
Author(s):  
Vineet Bhatt ◽  
Anwesha Mohapatra ◽  
Swadha Anand ◽  
Bhusan K. Kuntal ◽  
Sharmila S. Mande

2021 ◽  
Author(s):  
Cara Magnabosco

<p>Traditionally, the biogeochemical information preserved in the rock record has been used to study the environmental conditions of Earth’s past. There is however another important record of Earth’s history that is only just beginning to be explored: the genomes of contemporary organisms (i.e. the genetic record). The genetic record is an under-utilized tool for studying Earth History. Like the rock record, the genomes of microorganisms have been imprinted with information regarding our changing planet. In this presentation, we will describe a framework for accessing and interpreting the “genetic scars” imprinted on the genomes of microorganisms to identify the timing of the Great Oxidation Event (GOE) independent of the geochemical record. This approach combines ideas from systems biology and data science to infer the timing of major changes in the evolution of microbial lineages and metabolic pathways. Briefly, a horizontal gene transfer constrained molecular clock provides timeline for major speciation events within the bacterial tree of life which can be used to date the emergence of specific protein families related to oxygenic photosynthesis and oxygen consumption. A feature selection algorithm for metabolic networks allows us to generalise this technique beyond the GOE and will enable us to better interpret isotope anomalies in the geochemical record.</p>


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