ECMpy, a Simplified Workflow for Constructing Enzymatic Constrained Metabolic Network Model

Genome-scale metabolic models (GEMs) have been widely used for the phenotypic prediction of microorganisms. However, the lack of other constraints in the stoichiometric model often leads to a large metabolic solution space being inaccessible. Inspired by previous studies that take an allocation of macromolecule resources into account, we developed a simplified Python-based workflow for constructing enzymatic constrained metabolic network model (ECMpy) and constructed an enzyme-constrained model for Escherichia coli (eciML1515) by directly adding a total enzyme amount constraint in the latest version of GEM for E. coli (iML1515), considering the protein subunit composition in the reaction, and automated calibration of enzyme kinetic parameters. Using eciML1515, we predicted the overflow metabolism of E. coli and revealed that redox balance was the key reason for the difference between E. coli and Saccharomyces cerevisiae in overflow metabolism. The growth rate predictions on 24 single-carbon sources were improved significantly when compared with other enzyme-constrained models of E. coli. Finally, we revealed the tradeoff between enzyme usage efficiency and biomass yield by exploring the metabolic behaviours under different substrate consumption rates. Enzyme-constrained models can improve simulation accuracy and thus can predict cellular phenotypes under various genetic perturbations more precisely, providing reliable guidance for metabolic engineering.

ECMpy, a Simplified Workflow for Constructing Enzymatic Constrained Metabolic Network Model

Genome-scale metabolic models (GEMs) have been widely used for phenotypic prediction of microorganisms. However, the lack of other constraints in the stoichiometric model often leads to a large metabolic solution space inaccessible. Inspired by previous studies that take allocation of macromolecule resources into account, we developed a simplified Python-based workflow for constructing enzymatic constrained metabolic network model (ECMpy) and constructed an enzyme-constrained model for Escherichia coli (eciML1515) by directly adding a total enzyme amount constraint in the latest version of GEM for E. coli (iML1515), considering the protein subunit composition in the reaction, and automated calibration of enzyme kinetic parameters. Using eciML1515, we predicted the overflow metabolism of E. coli and revealed that redox balance was the key reason for the difference between E. coli and Saccharomyces cerevisiae in overflow metabolism. The growth rate predictions on 24 single-carbon sources were improved significantly when compared with other enzyme-constrained models of E. coli. Finally, we revealed the tradeoff between enzyme usage efficiency and biomass yield by exploring the metabolic behaviors under different substrate consumption rates. Enzyme-constrained models can improve simulation accuracy and thus can predict cellular phenotypes under various genetic perturbations more precisely, providing reliable guidance for metabolic engineering.

bmggum: An R Package for Bayesian Estimation of the Multidimensional Generalized Graded Unfolding Model With Covariates

Over the past couple of decades, there has been an increasing interest in adopting ideal point models to represent noncognitive constructs, as they have been demonstrated to better measure typical behaviors than traditional dominance models do. The generalized graded unfolding model ( GGUM) has consistently been the most popular ideal point model among researchers and practitioners. However, the GGUM2004 software and the later developed GGUM package in R can only handle unidimensional models despite the fact that many noncognitive constructs are multidimensional in nature. In addition, GGUM2004 and the GGUM package often yield unreasonable estimates of item parameters and standard errors. To address these issues, we developed the new open-source bmggum R package that is capable of estimating both unidimensional and multidimensional GGUM using a fully Bayesian approach, with supporting capabilities of stabilizing parameterization, incorporating person covariates, estimating constrained models, providing fit diagnostics, producing convergence metrics, and effectively handling missing data.

Enzyme-constrained models predict the dynamics of Saccharomyces cerevisiae growth in continuous, batch and fed-batch bioreactors

Genome-scale, constraint-based models (GEM) and their derivatives are commonly used to model and gain insights into microbial metabolism. Often, however, their accuracy and predictive power are limited and enable only approximate designs. To improve their usefulness for strain and bio-process design, we studied here their capacity to accurately predict metabolic changes in response to operational conditions in a bioreactor, as well as intracellular, active reactions. We used flux balance analysis (FBA) and dynamic FBA (dFBA) to predict growth dynamics of the model organism Saccharomyces cerevisiae under different industrially relevant conditions. We compared simulations with the latest developed GEM for this organism (Yeast8) and its enzyme-constrained version (ecYeast8) herein described with experimental data and found that ecYeast8 outperforms Yeast8 in all the simulations. EcYeast8 was able to predict well-known traits of yeast metabolism including the onset of the Crabtree effect, the order of substrate consumption during mixed carbon cultivation and production of a target metabolite. We showed how the combination of ecGEM and dFBA links reactor operation and genetic modifications to flux predictions, enabling the prediction of yields and productivities of different strains and (dynamic) production processes. Additionally, we present flux sampling as a tool to analyze flux predictions of ecGEM, of major importance for strain design applications. We showed that constraining protein availability substantially improves accuracy of the description of the metabolic state of the cell under dynamic conditions. This therefore enables more realistic and faithful designs of industrially relevant cell-based processes and, thus, the usefulness of such models

Reconstruction of a catalogue of genome-scale metabolic models with enzymatic constraints using GECKO 2.0

Genome-scale metabolic models (GEMs) have been widely used for quantitative exploration of the relation between genotype and phenotype. Streamlined integration of enzyme constraints and proteomics data into GEMs was first enabled by the GECKO method, allowing the study of phenotypes constrained by protein limitations. Here, we upgraded the GECKO toolbox in order to enhance models with enzyme and proteomics constraints for any organism with an available GEM reconstruction. With this, enzyme-constrained models (ecModels) for the budding yeasts Saccharomyces cerevisiae, Yarrowia lipolytica and Kluyveromyces marxianus were generated, aiming to study their long-term adaptation to several stress factors by incorporation of proteomics data. Predictions revealed that upregulation and high saturation of enzymes in amino acid metabolism were found to be common across organisms and conditions, suggesting the relevance of metabolic robustness in contrast to optimal protein utilization as a cellular objective for microbial growth under stress and nutrient-limited conditions. The functionality of GECKO was further developed by the implementation of an automated framework for continuous and version-controlled update of ecModels, which was validated by producing additional high-quality ecModels for Escherichia coli and Homo sapiens. These efforts aim to facilitate the utilization of ecModels in basic science, metabolic engineering and synthetic biology purposes.

Approaches to Revealing the Neural Basis of Muscle Synergies: A Review and A Critique

The central nervous system (CNS) may produce coordinated motor outputs via the combination of motor modules representable as muscle synergies. Identification of muscle synergies has hitherto relied on applying factorization algorithms to multi-muscle electromyographic data (EMGs) recorded during motor behaviors. Recent studies have attempted to validate the neural basis of the muscle synergies identified by independently retrieving the muscle synergies through CNS manipulations and analytic techniques such as spike-triggered averaging of EMGs. Experimental data have demonstrated the pivotal role of the spinal premotor interneurons in the synergies' organization and the presence of motor cortical loci whose stimulations offer access to the synergies, but whether the motor cortex is also involved in organizing the synergies has remained unsettled. We argue that one difficulty inherent in current approaches to probing the synergies' neural basis is that the EMG generative model based on linear combination of synergies and the decomposition algorithms used for synergy identification are not grounded on enough prior knowledge from neurophysiology. Progress may be facilitated by constraining or updating the model and algorithms with knowledge derived directly from CNS manipulations or recordings. An investigative framework based on evaluating the relevance of neurophysiologically constrained models of muscle synergies to natural motor behaviors will allow a more sophisticated understanding of motor modularity, which will help the community move forward from the current debate on the neural versus non-neural origin of muscle synergies.

Reconstruction of a catalogue of genome-scale metabolic models with enzymatic constraints using GECKO 2.0

Genome-scale metabolic models (GEMs) have been widely used for quantitative exploration of the relation between genotype and phenotype. Streamlined integration of enzyme constraints and proteomics data into GEMs was first enabled by the GECKO method, allowing the study of phenotypes constrained by protein limitations. Here, we upgraded the GECKO toolbox in order to enhance models with enzyme and proteomics constraints for any organism with an available GEM reconstruction. With this, enzyme-constrained models (ecModels) for the budding yeasts Saccharomyces cerevisiae, Yarrowia lipolytica and Kluyveromyces marxianus were generated, aiming to study their long-term adaptation to several stress factors by incorporation of proteomics data. Predictions revealed that upregulation and high saturation of enzymes in amino acid metabolism were found to be common across organisms and conditions, suggesting the relevance of metabolic robustness in contrast to optimal protein utilization as a cellular objective for microbial growth under stress and nutrient-limited conditions. The functionality of GECKO was further developed by the implementation of an automated framework for continuous and version-controlled update of ecModels, which was validated by producing additional high-quality ecModels for Escherichia coli and Homo sapiens. These efforts aim to facilitate the utilization of ecModels in basic science, metabolic engineering and synthetic biology purposes.

3D Petrophysical Modelling Of Queen Field, Onshore Niger Delta, Nigeria

Petrophysical-Modelling is indispensable in upstream Projects, considering the high cost, risks and uncertainties associated with this sector. Petrophysical qualities for Queen Field was modeled using Information obtained and analyzed from well-logs and 3-D Seismic data. Coarse-grain, Medium- grain and fine-grain Sands as well as Shale were all delineated by GR log. Results of petrophysical evaluation conducted on seven reservoir intervals correlated across the field showed that; Shale volume was below 35%, Total Porosity are > 20% Effective Porosity are >15% Permeability is > 380.00mD all of this conforms to excellent reservoir quantity. Seismic interpretation showed the presence of synthetic and antithetic faults. Two horizons were mapped on seismic data and utilized for modeling. These models were the framework for facies and petrophysical properties distribution. Facies models were generated using sequential indicator simulation while petrophysical properties were generated using sequential gaussian simulation algorithm. A comparison was further done between facies constrained and non-facies constrained models. It was found that for Porosity, Permeability, Water of Saturation and Shale Volume Models not constrained to facies all showed overestimated Models, in addition Stochastic STOIIP not constrained to facies gave an Over Estimated P50 value for Surface I and O Reservoir Interval as 624.028M, 76.28MM, when compared to Stochastic Hydrocarbon STOIIP when constrained to facies that showed Stochastic P50 value of 513,247 and 67.04MM for surface I and O and Deterministic STOIIP of 742.90M and 87.88MM. This study validates the practice of constraining Petrophysical model to facies available on the field as the best practice. Keywords: Queen Field, Onshore, Niger Delta, 3D Petrophysical.