Abstract Background COnstraint-Based Reconstruction and Analysis (COBRA) methods are widely used for genome-scale modeling of metabolic networks in both prokaryotes eukaryotes. Due to the successes with metabolism, there is an increasing effort apply COBRA reconstruct analyze integrated models cellular processes. The Toolbox MATLAB a leading software package analysis metabolism; however, it was not designed elegantly capture complexity inherent biological lacks integration framework...

Genome-scale metabolic models are mathematically-structured knowledge bases that can be used to predict pathway usage and growth phenotypes. Furthermore, they generate test hypotheses when integrated with experimental data. To maximize the value of these models, centralized repositories high-quality must established, adhere established standards model components linked relevant databases. Tools for visualization further enhance their utility. meet needs, we present BiGG Models...

Escher is a web application for visualizing data on biological pathways. Three key features make uniquely effective tool pathway visualization. First, users can rapidly design new maps. provides suggestions based user and genome-scale models, so draw pathways in semi-automated way. Second, visualize related to genes or proteins the associated reactions pathways, using rules that define which enzymes catalyze each reaction. Thus, identify trends common genomic types (e.g. RNA-Seq, proteomics,...

ABSTRACT Adaptive laboratory evolution (ALE) has emerged as an effective tool for scientific discovery and addressing biotechnological needs. Much of ALE's utility is derived from reproducibly obtained fitness increases. Identifying causal genetic changes their combinatorial effects challenging time-consuming. Understanding how these enable increased can be difficult. A series approaches that address challenges was developed demonstrated using Escherichia coli K-12 MG1655 on glucose minimal...

Abstract Rapid growth in size and complexity of biological data sets has led to the ‘Big Data Knowledge’ challenge. We develop advanced integration methods for multi-level analysis genomic, transcriptomic, ribosomal profiling, proteomic fluxomic data. First, we show that pairwise primary omics reveals regularities tie cellular processes together Escherichia coli : number protein molecules made per mRNA transcript ribosomes required translated molecule. Second, genome-scale models, based on...

The metabolic capabilities of acetogens to ferment a wide range sugars, grow autotrophically on H2/CO2, and more importantly synthesis gas (H2/CO/CO2) make them very attractive candidates as production hosts for biofuels biocommodities. Acetogenic metabolism is considered one the earliest modes bacterial metabolism. A thorough understanding various factors governing metabolism, in particular energy conservation mechanisms, critical engineering targeted desired chemicals.Here, we present...

Adaptive laboratory evolution (ALE) has emerged as a valuable method by which to investigate microbial adaptation desired environment. Here, we performed ALE 42 °C of ten parallel populations Escherichia coli K-12 MG1655 grown in glucose minimal media. Tightly controlled experimental conditions allowed selection based on exponential-phase growth rate, yielding strains that uniformly converged toward similar phenotype along distinct genetic paths. Adapted possessed few 6 and many 55...

Genome-scale models of metabolism and macromolecular expression (ME-models) explicitly compute the optimal proteome composition a growing cell. ME-models expand upon well-established genome-scale (M-models), they enable new fundamental understanding cellular growth. have increased predictive capabilities accuracy due to their inclusion biosynthetic costs for machinery life, but come with significant increase in model size complexity. This challenge results which are both difficult...

Abstract Motivation: Genome-scale metabolic models have been used extensively to investigate alterations in cellular metabolism. The accuracy of these represent metabolism specific conditions has improved by constraining the model with omics data sources. However, few practical methods for integrating metabolomics other sources into genome-scale developed. Results: GIM3E (Gene Inactivation Moderated Metabolism, Metabolomics and Expression) is an algorithm that enables development...

Microbial electrosynthesis, the conversion of carbon dioxide to organic molecules using electricity, has recently been demonstrated for acetogenic microorganisms, such as Sporomusa ovata. The energy reduction originates from hydrolysis water on anode, requiring a sufficiently low potential. Here we evaluate use sulfide an electron source microbial electrosynthesis. Abiotically oxidation anode yields two electrons. product, elemental sulfur, can be further oxidized sulfate by Desulfobulbus...

Significance Organisms have evolved to take advantage of their environment. Enzymes drive this adaptability by displaying flexibility in terms substrate specificity and catalytic promiscuity. This enzyme promiscuity has been observed a limited number laboratory experiments; however, larger underground network reactions may occur within cell below the level detection. It is not until cell’s metabolic capabilities are probed that these novel functions come light. In study, workflow presented...

Determining how facultative anaerobic organisms sense and direct cellular responses to electron acceptor availability has been a subject of intense study. However, even in the model organism Escherichia coli, established mechanisms only explain small fraction hundreds genes that are regulated during shifts. Here we propose qualitative accounts for full breadth by detailing two global transcription factors (TFs), ArcA Fnr E. key metabolic redox ratios act on genome-wide basis regulate...

Genome-scale models of metabolism and macromolecular expression (ME models) enable systems-level computation proteome allocation coupled to metabolic phenotype.We develop DynamicME, an algorithm enabling time-course simulation cell protein expression. DynamicME correctly predicted the substrate utilization hierarchy on a mixed carbon medium. We also found good agreement between measured profiles. ME involve considerably more parameters than (M models). thus generate ensemble (each model...

A simple method for the electrochemical detection of TATA-binding protein is demonstrated at DNA-modified microelectrodes. The assay general and based on interruption DNA-mediated charge transport to Nile Blue, a redox-active probe covalently attached DNA base pair stack. Nanomolar quantities TATA binding can be detected microelectrodes even in presence micromolar amounts bovine serum albumin, EndonucleaseIII, or Bam HI methyltransferase. scheme outlined provides basis sensitive electrical...

The unique capability of acetogens to ferment a broad range substrates renders them ideal candidates for the biotechnological production commodity chemicals. In particular ability grow with H2:CO2 or syngas (a mixture H2/CO/CO2) makes these microorganisms chassis sustainable bioproduction. However, advanced design strategies are currently hampered by incomplete knowledge about their physiology and our inability accurately predict phenotypes. Here we describe reconstruction novel genome-scale...

Genome-scale models of metabolism and macromolecular expression (ME) significantly expand the scope predictive capabilities constraint-based modeling. ME present considerable computational challenges: they are much (>30 times) larger than corresponding metabolic reconstructions (M models), multiscale, growth maximization is a nonlinear programming (NLP) problem, mainly due to macromolecule dilution constraints.Here, we address these challenges. We develop fast numerically reliable solution...

Abstract Pathways are a universal paradigm for functionally describing cellular processes. Even though advances in high‐throughput data generation have transformed biology, the core of our biological understanding, and hence interpretation, is still predicated on human‐defined pathways. Here, we introduce an unbiased, pathway structure genome‐scale metabolic networks defined based principles parsimony that do not mimic canonical textbook Instead, these minimal pathways better describe...

Significance Defining a core functional proteome supporting the living process has importance for both developing fundamental understanding of cell functions and synthetic biology applications. Comparative genomics been primary approach to achieve such definition. Here, we use genome-scale models define that computationally supports basic cellular function. This metabolism protein expression, defined through systems methods, is validated characterized by using multiple disparate data types.

Abstract Integrating omics data to refine or make context-specific models is an active field of constraint-based modeling. Proteomics now cover over 95% the Escherichia coli proteome by mass. Genome-scale Metabolism and macromolecular Expression (ME) compute allocation linked metabolism fitness. Using proteomics data, we formulated constraints for key sectors in ME model. The resulting calibrated model effectively computed “generalist” (wild-type) E. phenotype across diverse growth...

Numerous in vitro studies have yielded a refined picture of the structural and molecular associations between Cyclic-AMP receptor protein (Crp), DNA motif, RNA polymerase (RNAP) holoenzyme. In this study, high-resolution ChIP-exonuclease (ChIP-exo) was applied to study Crp binding vivo at genome-scale. Surprisingly, found provide little no protection motif under activating conditions. Instead, demonstrated patterns that closely resembled those generated by σ70. The both σ70 are indicative...

The establishment of experimental conditions for transcriptional regulator network (TRN) reconstruction in bacteria continues to be impeded by the limited knowledge activating transcription factors (TFs). Here, we present a novel genome-scale model-driven workflow designing conditions, which optimally activate specific TFs. Our was applied elucidate regulation under nitrogen limitation Nac and NtrC,

Abstract Genome-scale models of metabolism and macromolecular expression (ME-models) explicitly compute the optimal proteome composition a growing cell. ME-models expand upon well-established genome-scale (M-models), they enable new exciting insights that are fundamental to understanding basis cellular growth. have increased predictive capabilities accuracy due their inclusion biosynthetic costs for machinery life, but come with significant increase in model size complexity. This challenge...

Background: At a time of worldwide nursing shortage, is raising questions about the issue increasing nurses' turnover. The literatures have shown that stronger intention to leave as consequence job dissatisfaction may lead actual Therefore, it be crucial understand satisfaction issue, this key factor in working place and low commitment. Aim Objective: This study examined factors determine which are personal, environmental organizational components relation those on Coronary Care Unit their...