Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Fast and flexible analysis of linked microbiome data with mako

A Publisher Correction to this article was published on 23 March 2022

This article has been updated

Abstract

Mako is a software tool that converts microbiome data and networks into a graph database and visualizes query results, thus allowing users without programming knowledge to carry out network-based queries. Mako is accompanied by a database compiled from 60 microbiome studies that is easily extended with the user’s own data. We illustrate mako’s strengths by enumerating association partners linked to propionate production and comparing frequencies of different network motifs across habitat types.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Features of mako.
Fig. 2: Motif identification with Neo4j.

Similar content being viewed by others

Data availability

The complete Neo4j database used in this paper has been used to generate a Neo4j dump file. An archived version of this file has been submitted to Zenodo17. Instructions for reconstructing this database are available in mako’s documentation. All BIOM files were downloaded from QIITA6 and a full overview of these studies can be found in Supplementary Table 1.

Code availability

The latest version of the mako software can be downloaded via https://github.com/ramellose/mako/. An archived version, including the script used to quantify motifs in the Neo4j database, has been submitted to Zenodo17. All mako source code and the included script are available under the Apache License 2.0. An extensive manual for running mako and Neo4j (via Docker) is available via https://ramellose.github.io/mako_docs/. Additionally, an accompanying compute capsule allows a demo of mako and a Neo4j database to be run without requiring any installations21.

Change history

References

  1. Röttjers, L. & Faust, K. From hairballs to hypotheses–biological insights from microbial networks. FEMS Microbiol. Rev. 42, 761–780 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Jackson, M. A. et al. Detection of stable community structures within gut microbiota co-occurrence networks from different human populations. PeerJ 6, e4303 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Wang, H. et al. Combined use of network inference tools identifies ecologically meaningful bacterial associations in a paddy soil. Soil Biol. Biochem. 105, 227–235 (2017).

    Article  CAS  Google Scholar 

  4. Poisot, T. et al. mangal–making ecological network analysis simple. Ecography 39, 384–390 (2016).

    Article  Google Scholar 

  5. Szklarczyk, D. et al. String v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 47, D607–D613 (2019).

    Article  CAS  PubMed  Google Scholar 

  6. Gonzalez, A. et al. QIITA: rapid, web-enabled microbiome meta-analysis. Nat. Methods 15, 796–798 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Miller, J. J. Graph database applications and concepts with neo4j. In Proc. Southern Association for Information Systems Conference, Atlanta, GA, USA Vol. 2324 (ed. Fitzpatrick, L.) 141–147 (AIS, 2013).

  8. Bansal, S. K. Towards a semantic extract-transform-load (ETL) framework for big data integration. In Proc. 2014 IEEE International Congress on Big Data (eds Chen, P. & Jain, H.) 522–529 (IEEE, 2014).

  9. Noy, N. F. et al. Creating semantic web contents with protege-2000. IEEE Intell. Syst. 16, 60–71 (2001).

    Article  Google Scholar 

  10. Kerr, B., Riley, M. A., Feldman, M. W. & Bohannan, B. J. Local dispersal promotes biodiversity in a real-life game of rock–paper–scissors. Nature 418, 171–174 (2002).

    Article  CAS  PubMed  Google Scholar 

  11. Ma, Z. S. & Ye, D. Trios-promising in silico biomarkers for differentiating the effect of disease on the human microbiome network. Sci. Rep. 7, 13259 (2017).

    Article  PubMed  Google Scholar 

  12. Thompson, L. R. et al. A communal catalogue reveals earth’s multiscale microbial diversity. Nature 551, 457–463 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ma, B. et al. Earth microbial co-occurrence network reveals interconnection pattern across microbiomes. Microbiome 8, 82 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Faust, K. et al. Cross-biome comparison of microbial association networks. Front. Microbiol. 6, 1200 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Louis, P. & Flint, H. J. Formation of propionate and butyrate by the human colonic microbiota. Environ. Microbiol. 19, 29–41 (2017).

    Article  CAS  PubMed  Google Scholar 

  16. Tackmann, J., Rodrigues, J. F. M. & von Mering, C. Rapid inference of direct interactions in large-scale ecological networks from heterogeneous microbial sequencing data. Cell Syst. 9, 286–296 (2019).

    Article  CAS  PubMed  Google Scholar 

  17. Röttjers, L. & Faust, K. Fast and flexible analysis of linked microbiome data with mako. Zenodo https://doi.org/10.5281/zenodo.4946425 (2021).

  18. Conway, J. R., Lex, A. & Gehlenborg, N. Upsetr: an R package for the visualization of intersecting sets and their properties. Bioinformatics 33, 2938–2940 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sioutos, N. et al. Nci thesaurus: a semantic model integrating cancer-related clinical and molecular information. J. Biomed. Inform. 40, 30–43 (2007).

    Article  CAS  PubMed  Google Scholar 

  20. Summer, G. et al. cyneo4j: connecting neo4j and cytoscape. Bioinformatics 31, 3868–3869 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Röttjers, L. & Faust, K. Fast and flexible analysis of linked microbiome data with mako. Code Ocean https://doi.org/10.24433/CO.0482418.v1 (2021).

Download references

Acknowledgements

This project was supported by the KU Leuven under grant no. STG/16/006. K.F. has received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation program under grant agreement no. 801747.

Author information

Authors and Affiliations

Authors

Contributions

L.R. developed the software, carried out the case studies and drafted the paper. K.F. contributed to the design of the software and the case studies, and provided substantial revisions of the paper. Both authors read and approved the final paper.

Corresponding author

Correspondence to Karoline Faust.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information Nature Methods thanks Jianguo Xia and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available. Lin Tang was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Reporting Summary

Peer Review File

Supplementary Table 1

Excel file containing a summary of all downloaded BIOM files and derived network size (in terms of node number and edge number) used for the study ‘Fast and flexible analysis of linked microbiome data with mako’.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Röttjers, L., Faust, K. Fast and flexible analysis of linked microbiome data with mako. Nat Methods 19, 51–54 (2022). https://doi.org/10.1038/s41592-021-01335-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41592-021-01335-9

This article is cited by

Search

Quick links

Nature Briefing Microbiology

Sign up for the Nature Briefing: Microbiology newsletter — what matters in microbiology research, free to your inbox weekly.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing: Microbiology