An insight to flux-balance analysis for biochemical networks

Anand, Shreya; Mukherjee, Koel; Padmanabhan, Padmini

doi:10.1080/02648725.2020.1847440

Cited by 36 publications

(18 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We aimed to evaluate whether protein concentrations used as constraints will result in meaningful relative maximum capacities of reactions in the neuron and astrocyte. We provided a detailed description for this part in the Supplementary Presentation ( McKenna et al, 2006 ; Çakir et al, 2007 ; Lewis et al, 2010 ; Orth et al, 2010 ; Sigurdsson et al, 2010 ; Schellenberger et al, 2011 ; Ebrahim et al, 2013 ; Desouki et al, 2015 ; Gavai et al, 2015 ; King et al, 2015 ; O’Brien and Palsson, 2015 ; Noor et al, 2016 ; DiNuzzo et al, 2017 ; Martín-Jiménez et al, 2017 ; Sánchez et al, 2017 ; Heckmann et al, 2018 ; Supandi and van Beek, 2018 ; Tian and Reed, 2018 ; Lularevic et al, 2019 ; Pandey et al, 2019 ; Anand et al, 2020 ; Gurobi Optimization, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

A Standardized Brain Molecular Atlas: A Resource for Systems Modeling and Simulation

Shichkova

Coggan

Markram

et al. 2021

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Accurate molecular concentrations are essential for reliable analyses of biochemical networks and the creation of predictive models for molecular and systems biology, yet protein and metabolite concentrations used in such models are often poorly constrained or irreproducible. Challenges of using data from different sources include conflicts in nomenclature and units, as well as discrepancies in experimental procedures, data processing and implementation of the model. To obtain a consistent estimate of protein and metabolite levels, we integrated and normalized data from a large variety of sources to calculate Adjusted Molecular Concentrations. We found a high degree of reproducibility and consistency of many molecular species across brain regions and cell types, consistent with tight homeostatic regulation. We demonstrated the value of this normalization with differential protein expression analyses related to neurodegenerative diseases, brain regions and cell types. We also used the results in proof-of-concept simulations of brain energy metabolism. The standardized Brain Molecular Atlas overcomes the obstacles of missing or inconsistent data to support systems biology research and is provided as a resource for biomolecular modeling.

show abstract

Section: Methodsmentioning

confidence: 99%

A Standardized Brain Molecular Atlas: A Resource for Systems Modeling and Simulation

Shichkova

Coggan

Markram

et al. 2021

Front. Mol. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Consequently, so-called constraint-based methods have come to the fore. Chief among these is flux balance analysis (FBA) [146,315,317,[337][338][339][340][341].…”

Section: Systems Modelling For Host Engineeringmentioning

confidence: 99%

“…Software for performing FBA is also more or less widely available [340,349], the generic COBRA toolboxes [347,[350][351][352][353] being especially popular. Such software is much aided by the development of various kinds of linguistic standards for describing systems biology models, such as BioPAX [354][355][356][357] (http://www.biopax.org/) and SBML [358] (http://sbml.org/Main_Page).…”

Section: Systems Modelling For Host Engineeringmentioning

confidence: 99%

Intelligent host engineering for metabolic flux optimisation in biotechnology

Munro

Kell

2021

Biochemical Journal

View full text Add to dashboard Cite

Optimising the function of a protein of length N amino acids by directed evolution involves navigating a ‘search space’ of possible sequences of some 20N. Optimising the expression levels of P proteins that materially affect host performance, each of which might also take 20 (logarithmically spaced) values, implies a similar search space of 20P. In this combinatorial sense, then, the problems of directed protein evolution and of host engineering are broadly equivalent. In practice, however, they have different means for avoiding the inevitable difficulties of implementation. The spare capacity exhibited in metabolic networks implies that host engineering may admit substantial increases in flux to targets of interest. Thus, we rehearse the relevant issues for those wishing to understand and exploit those modern genome-wide host engineering tools and thinking that have been designed and developed to optimise fluxes towards desirable products in biotechnological processes, with a focus on microbial systems. The aim throughput is ‘making such biology predictable’. Strategies have been aimed at both transcription and translation, especially for regulatory processes that can affect multiple targets. However, because there is a limit on how much protein a cell can produce, increasing kcat in selected targets may be a better strategy than increasing protein expression levels for optimal host engineering.

show abstract

“…In metabolic networks, nodes represent metabolites whilst edges refer to enzymes that catalyse metabolic reactions between the substrate and product metabolites ( Vidal et al, 2011 ). The most common way of analysing a metabolic network is using flux-balance analysis, which involves calculating the flow of metabolites through the network in steady state ( Orth et al, 2010 ; Anand et al, 2020 ). ( Figure 3 ).…”

Section: Use Of Network Biology Approaches In Ibdmentioning

confidence: 99%

Network Biology Approaches to Achieve Precision Medicine in Inflammatory Bowel Disease

et al. 2021

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) is a chronic immune-mediated condition arising due to complex interactions between multiple genetic and environmental factors. Despite recent advances, the pathogenesis of the condition is not fully understood and patients still experience suboptimal clinical outcomes. Over the past few years, investigators are increasingly capturing multi-omics data from patient cohorts to better characterise the disease. However, reaching clinically translatable endpoints from these complex multi-omics datasets is an arduous task. Network biology, a branch of systems biology that utilises mathematical graph theory to represent, integrate and analyse biological data through networks, will be key to addressing this challenge. In this narrative review, we provide an overview of various types of network biology approaches that have been utilised in IBD including protein-protein interaction networks, metabolic networks, gene regulatory networks and gene co-expression networks. We also include examples of multi-layered networks that have combined various network types to gain deeper insights into IBD pathogenesis. Finally, we discuss the need to incorporate other data sources including metabolomic, histopathological, and high-quality clinical meta-data. Together with more robust network data integration and analysis frameworks, such efforts have the potential to realise the key goal of precision medicine in IBD.

show abstract

An insight to flux-balance analysis for biochemical networks

Cited by 36 publications

References 86 publications

A Standardized Brain Molecular Atlas: A Resource for Systems Modeling and Simulation

A Standardized Brain Molecular Atlas: A Resource for Systems Modeling and Simulation

Intelligent host engineering for metabolic flux optimisation in biotechnology

Network Biology Approaches to Achieve Precision Medicine in Inflammatory Bowel Disease

Contact Info

Product

Resources

About