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Record W2606897259 · doi:10.1371/journal.pcbi.1005409

From elementary flux modes to elementary flux vectors: Metabolic pathway analysis with arbitrary linear flux constraints

2017· review· en· W2606897259 on OpenAlexaff
Steffen Klamt, Georg Regensburger, Matthias P. Gerstl, Christian Jungreuthmayer, Stefan Schuster, Radhakrishnan Mahadevan, Jürgen Zanghellini, Stefan C. Müller

Bibliographic record

VenuePLoS Computational Biology · 2017
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMicrobial Metabolic Engineering and Bioproduction
Canadian institutionsUniversity of Toronto
FundersGerman Network for Bioinformatics InfrastructureStandortagentur TirolBundesministerium für Verkehr, Innovation und TechnologieMax-Planck-GesellschaftBundesministerium für Wissenschaft, Forschung und WirtschaftAustrian Science FundBundesministerium für Bildung und ForschungAmt der NÖ Landesregierung
KeywordsFlux (metallurgy)Flux balance analysisConstraint (computer-aided design)Metabolic networkPhysicsMetabolic flux analysisComputer scienceState (computer science)Applied mathematicsMathematicsAlgorithmGeometryChemistry

Abstract

fetched live from OpenAlex

Elementary flux modes (EFMs) emerged as a formal concept to describe metabolic pathways and have become an established tool for constraint-based modeling and metabolic network analysis. EFMs are characteristic (support-minimal) vectors of the flux cone that contains all feasible steady-state flux vectors of a given metabolic network. EFMs account for (homogeneous) linear constraints arising from reaction irreversibilities and the assumption of steady state; however, other (inhomogeneous) linear constraints, such as minimal and maximal reaction rates frequently used by other constraint-based techniques (such as flux balance analysis [FBA]), cannot be directly integrated. These additional constraints further restrict the space of feasible flux vectors and turn the flux cone into a general flux polyhedron in which the concept of EFMs is not directly applicable anymore. For this reason, there has been a conceptual gap between EFM-based (pathway) analysis methods and linear optimization (FBA) techniques, as they operate on different geometric objects. One approach to overcome these limitations was proposed ten years ago and is based on the concept of elementary flux vectors (EFVs). Only recently has the community started to recognize the potential of EFVs for metabolic network analysis. In fact, EFVs exactly represent the conceptual development required to generalize the idea of EFMs from flux cones to flux polyhedra. This work aims to present a concise theoretical and practical introduction to EFVs that is accessible to a broad audience. We highlight the close relationship between EFMs and EFVs and demonstrate that almost all applications of EFMs (in flux cones) are possible for EFVs (in flux polyhedra) as well. In fact, certain properties can only be studied with EFVs. Thus, we conclude that EFVs provide a powerful and unifying framework for constraint-based modeling of metabolic networks.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.004
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Theoretical or conceptual · Consensus signal: Theoretical or conceptual
GenreCandidate signal: Review · Consensus signal: none
Teacher disagreement score0.004
Threshold uncertainty score0.013

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.004
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0020.002
Science and technology studies0.0010.002
Scholarly communication0.0020.004
Open science0.0010.002
Research integrity0.0010.003
Insufficient payload (model declined to judge)0.0040.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.035
GPT teacher head0.307
Teacher spread0.272 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designTheoretical or conceptual
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations77
Published2017
Admission routes1
Has abstractyes

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