Evidence map›Paper›PMID 30567498›Full record

ArticleBMC genomics2018

Combining multiple functional annotation tools increases coverage of metabolic annotation.

Marc Griesemer, Jeffrey A Kimbrel, Carol E Zhou, Ali Navid, Patrik D'haeseleer

Abstract read
In one paragraph

Article in BMC genomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing 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

35 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Comparative Genomic and Functional Profiling of ECM-Targeting Enzymes inbioRxiv : the preprint server for biology · 2026
    Article
  5. Functional Annotation Workflow for Fungal Transcriptomes.Journal of fungi (Basel, Switzerland) · 2026
    Article
  6. Article
  7. Review
  8. Frontiers in microbiology · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Multi-scale models of whole cells: progress and challenges.Frontiers in cell and developmental biology · 2023
    Review
  15. An informatic workflow for the enhanced annotation of excretory/secretory proteins ofComputational and structural biotechnology journal · 2023
    Article
  16. KinMod database: a tool for investigating metabolic regulation.Database : the journal of biological databases and curation · 2022
    Article
  17. Article
  18. Article
  19. Article
  20. Article
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

5 authors.

Marc GriesemerBiosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, CA, 94551, USA.
Jeffrey A KimbrelBiosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, CA, 94551, USA.
Carol E ZhouGlobal Security Computing Applications Division, Lawrence Livermore National Laboratory, Livermore, CA, 94551, USA.
Ali NavidBiosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, CA, 94551, USA.
Patrik D'haeseleerBiosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, CA, 94551, USA. dhaeseleer2@llnl.gov.ORCID http://orcid.org/0000-0003-0007-8150

Funding

Biological and Environmental Research SCW1039-02National Nuclear Security Administration DE-AC52-07NA27344
6 · The paper itself

Abstract

backgroundGenome-scale metabolic modeling is a cornerstone of systems biology analysis of microbial organisms and communities, yet these genome-scale modeling efforts are invariably based on incomplete functional annotations. Annotated genomes typically contain 30-50% of genes without functional annotation, severely limiting our knowledge of the "parts lists" that the organisms have at their disposal. These incomplete annotations may be sufficient to derive a model of a core set of well-studied metabolic pathways that support growth in pure culture. However, pathways important for growth on unusual metabolites exchanged in complex microbial communities are often less understood, resulting in missing functional annotations in newly sequenced genomes.

resultsHere, we present results on a comprehensive reannotation of 27 bacterial reference genomes, focusing on enzymes with EC numbers annotated by KEGG, RAST, EFICAz, and the BRENDA enzyme database, and on membrane transport annotations by TransportDB, KEGG and RAST. Our analysis shows that annotation using multiple tools can result in a drastically larger metabolic network reconstruction, adding on average 40% more EC numbers, 3-8 times more substrate-specific transporters, and 37% more metabolic genes. These results are even more pronounced for bacterial species that are phylogenetically distant from well-studied model organisms such as E. coli.

conclusionsMetabolic annotations are often incomplete and inconsistent. Combining multiple functional annotation tools can greatly improve genome coverage and metabolic network size, especially for non-model organisms and non-core pathways.

Indexed as

Genome, BacterialMolecular Sequence AnnotationSoftwareBacteriaDatabases, GeneticGenomicsMetabolic Networks and PathwaysSystems BiologyEnzyme predictionFunctional annotationGenome annotationMetabolic modelingTransport prediction

Identifiers

PMID30567498
PMCPMC6299973

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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.