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Reply to "Challenges in modeling the human gut microbiome"

Nature Biotechnology volume 36, pages 686–691 (2018)Cite this article

Magnúsdóttir et al. reply:

Babaei et al1 raise several concerns related to our Resource of microbial genome-scale metabolic (GEM) reconstructions, AGORA, published in the January 2017 issue2. Although they claim that the AGORA reconstructions cannot be used directly for simulations, AGORA is a rich resource of metabolic reconstructions that can be converted into many condition-specific metabolic models by the application of condition-specific constraints. By publishing a metabolic reconstruction rather than a condition-specific metabolic model, the resource can be used for a myriad of applications. However, as a consequence, the user is responsible for setting constraints as appropriate to their biological questions and simulations. This is not only the case for AGORA reconstructions, but for most of the publicly deposited GEM reconstructions or derived condition-specific models3. In fact, this reusability of a reconstruction for many different biomedical and biotechnological applications is one of the reasons why the reconstruction and modeling approach has been so broadly adopted by the community.

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Figure 1: Growth rates of models under conditions constrained with the Western diet (minimum 0.0046 h−1, maximum 3.10 h−1, median 0.35 h−1), of generic reconstructions (minimum 11.4 h−1, maximum 255 h−1, median 76.9 h−1), and of the default downloaded collection (January 2017), which included a mix of condition-specific models and generic reconstructions (minimum 0.0045 h−1, maximum 255 h−1, median 59.7 h−1).
Figure 2: Blocked reactions and reactions involved in stoichiometrically balanced cycles (SBCs) in BiGG and AGORA reconstruction.
Figure 3: Histogram showing the Jaccard similarities between every pair of the 773 AGORA reconstructions, and of the 74 BiGG reconstructions.

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Authors and Affiliations

  1. Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg

    Stefanía Magnúsdóttir, Almut Heinken & Ines Thiele

  2. Division of Analytical Biosciences, Leiden Academic Centre for Drug Research, Faculty of Science, University of Leiden, Leiden, The Netherlands

    Ronan M T Fleming

Authors
  1. Stefanía Magnúsdóttir
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  2. Almut Heinken
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  3. Ronan M T Fleming
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  4. Ines Thiele
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Supplementary information

Supplementary Text and Figures

Supplementary Notes 1–3 and Supplementary Figures 1–4 (PDF 1029 kb)

Supplementary Table 1

The 74 BiGG reconstructions that were used in the analysis. (XLSX 33 kb)

Supplementary Table 2

Exchange reactions set when applying the Western diet and the lower bound constraints set to each reaction. (XLSX 12 kb)

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Magnúsdóttir, S., Heinken, A., Fleming, R. et al. Reply to "Challenges in modeling the human gut microbiome". Nat Biotechnol 36, 686–691 (2018). https://doi.org/10.1038/nbt.4212

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