Evidence map›Paper›PMID 36566974›Full record

ArticleMetabolic engineering2023

Guidelines for extracting biologically relevant context-specific metabolic models using gene expression data.

Saratram Gopalakrishnan, Chintan J Joshi, Miguel Á Valderrama-Gómez, Elcin Icten, Pablo Rolandi, William Johnson, Cleo Kontoravdi, Nathan E Lewis

Abstract read
In one paragraph

Article in Metabolic engineering, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed.

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  11. Yeast adapts to diverse ecological niches driven by genomics and metabolic reprogramming.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  16. Frontiers in systems biology · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Saratram GopalakrishnanDepartment of Pediatrics, University of California San Diego, United States.
Chintan J JoshiDepartment of Pediatrics, University of California San Diego, United States.
Miguel Á Valderrama-GómezDigital Integration and Predictive Technologies, Amgen Inc, United States.
Elcin IctenDigital Integration and Predictive Technologies, Amgen Inc, United States.
Pablo RolandiDigital Integration and Predictive Technologies, Amgen Inc, United States.
William JohnsonDigital Integration and Predictive Technologies, Amgen Inc, United States.
Cleo KontoravdiDepartment of Chemical Engineering, Imperial College London, UK.
Nathan E LewisDepartment of Pediatrics, University of California San Diego, United States; Department of Bioengineering, University of California San Diego, United States. Electronic address: nlewisres@ucsd.edu.

Funding

Unraveling the mammalian secretory pathway through systems biology and algorithm developmentR35GM119850 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LEWIS, NATHAN ENOCH · 2016 to 2025
$4.3M
NIGMS NIH HHS R35 GM119850
6 · The paper itself

Abstract

Genome-scale metabolic models comprehensively describe an organism's metabolism and can be tailored using omics data to model condition-specific physiology. The quality of context-specific models is impacted by (i) choice of algorithm and parameters and (ii) alternate context-specific models that equally explain the -omics data. Here we quantify the influence of alternate optima on microbial and mammalian model extraction using GIMME, iMAT, MBA, and mCADRE. We find that metabolic tasks defining an organism's phenotype must be explicitly and quantitatively protected. The scope of alternate models is strongly influenced by algorithm choice and the topological properties of the parent genome-scale model with fatty acid metabolism and intracellular metabolite transport contributing much to alternate solutions in all models. mCADRE extracted the most reproducible context-specific models and models generated using MBA had the most alternate solutions. There were fewer qualitatively different solutions generated by GIMME in E. coli, but these increased substantially in the mammalian models. Screening ensembles using a receiver operating characteristic plot identified the best-performing models. A comprehensive evaluation of models extracted using combinations of extraction methods and expression thresholds revealed that GIMME generated the best-performing models in E. coli, whereas mCADRE is better suited for complex mammalian models. These findings suggest guidelines for benchmarking -omics integration algorithms and motivate the development of a systematic workflow to enumerate alternate models and extract biologically relevant context-specific models.

Indexed as

Escherichia coliModels, BiologicalAnimalsGene ExpressionGenomeMammalsMetabolic Networks and PathwaysConstraint-based modelsContext-specific modelsMetabolic modelingModel extraction methodsSystems biology

Identifiers

PMID36566974
PMCPMC10258867

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.