Evidence map›Paper›PMID 29914471›Full record

ArticleBMC systems biology2018

How accurate is automated gap filling of metabolic models?

Peter D Karp, Daniel Weaver, Mario Latendresse

Abstract read
In one paragraph

Article in BMC systems biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
–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

27 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Preclinical techniques to investigate exercise training in vascular pathophysiology.American journal of physiology. Heart and circulatory physiology · 2021
    Pooled it
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  4. Evaluating plant growth-defense trade-offs by modeling the interaction between primary and secondary metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  8. Review
  9. Interactive tools for functional annotation of bacterial genomes.Database : the journal of biological databases and curation · 2024
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  11. Article
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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

3 authors.

Peter D KarpBioinformatics Research Group, SRI International, 333 Ravenswood Ave, Menlo Park, 94025, USA. pkarp@ai.sri.com.ORCID 0000-0002-5876-6418
Daniel WeaverBioinformatics Research Group, SRI International, 333 Ravenswood Ave, Menlo Park, 94025, USA.
Mario LatendresseBioinformatics Research Group, SRI International, 333 Ravenswood Ave, Menlo Park, 94025, USA.

Funding

The MetaCyc & BioCyc Pathway/Genome Databases (SRI Proposal ECU 14-630)R01GM080746 · NIGMS · SRI INTERNATIONAL · PI CASPI, RON, KARP, PETER D · 2007 to 2021
$15.6M
Robust Software Components for Model Organism DatabasesR01GM075742 · NIGMS · SRI INTERNATIONAL · PI KARP, PETER D · 2005 to 2019
$12.0M
NIGMS NIH HHS R01 GM075742
6 · The paper itself

Abstract

backgroundReaction gap filling is a computational technique for proposing the addition of reactions to genome-scale metabolic models to permit those models to run correctly. Gap filling completes what are otherwise incomplete models that lack fully connected metabolic networks. The models are incomplete because they are derived from annotated genomes in which not all enzymes have been identified. Here we compare the results of applying an automated likelihood-based gap filler within the Pathway Tools software with the results of manually gap filling the same metabolic model. Both gap-filling exercises were applied to the same genome-derived qualitative metabolic reconstruction for Bifidobacterium longum subsp. longum JCM 1217, and to the same modeling conditions - anaerobic growth under four nutrients producing 53 biomass metabolites.

resultsThe solution computed by the gap-filling program GenDev contained 12 reactions, but closer examination showed that solution was not minimal; two of the twelve reactions can be removed to yield a set of ten reactions that enable model growth. The manually curated solution contained 13 reactions, eight of which were shared with the 12-reaction computed solution. Thus, GenDev achieved recall of 61.5% and precision of 66.6%. These results suggest that although computational gap fillers are populating metabolic models with significant numbers of correct reactions, automatically gap-filled metabolic models also contain significant numbers of incorrect reactions.

conclusionsOur conclusion is that manual curation of gap-filler results is needed to obtain high-accuracy models. Many of the differences between the manual and automatic solutions resulted from using expert biological knowledge to direct the choice of reactions within the curated solution, such as reactions specific to the anaerobic lifestyle of B. longum.

Indexed as

MetabolismModels, BiologicalAlgorithmsAutomationBifidobacterium longumBiomassEvaluationFBAFlux balance analysisGap-filling

Identifiers

PMID29914471
PMCPMC6006690

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.