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AGORA2: Large scale reconstruction of the microbiome highlights wide-spread drug-metabolising capacities

View ORCID ProfileAlmut Heinken, Geeta Acharya, View ORCID ProfileDmitry A. Ravcheev, View ORCID ProfileJohannes Hertel, Malgorzata Nyga, Onyedika Emmanuel Okpala, Marcus Hogan, Stefanía Magnúsdóttir, Filippo Martinelli, German Preciat, Janaka N. Edirisinghe, Christopher S. Henry, View ORCID ProfileRonan M.T. Fleming, View ORCID ProfileInes Thiele
doi: https://doi.org/10.1101/2020.11.09.375451
Almut Heinken
1School of Medicine, National University of Galway, Galway, Ireland
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Geeta Acharya
2Integrated BioBank of Luxembourg, Dudelange, Luxembourg
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Dmitry A. Ravcheev
1School of Medicine, National University of Galway, Galway, Ireland
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Johannes Hertel
1School of Medicine, National University of Galway, Galway, Ireland
3Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
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Malgorzata Nyga
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Onyedika Emmanuel Okpala
4Czech University of Life Sciences Prague, Czech Republic
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Marcus Hogan
1School of Medicine, National University of Galway, Galway, Ireland
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Stefanía Magnúsdóttir
5Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
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Filippo Martinelli
1School of Medicine, National University of Galway, Galway, Ireland
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German Preciat
6Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands
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Janaka N. Edirisinghe
7Computation Institute, University of Chicago, Chicago, IL, USA
8Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, Illinois, USA
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Christopher S. Henry
8Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, Illinois, USA
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Ronan M.T. Fleming
1School of Medicine, National University of Galway, Galway, Ireland
6Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands
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Ines Thiele
1School of Medicine, National University of Galway, Galway, Ireland
9Division of Microbiology, National University of Galway, Galway, Ireland
10APC Microbiome Ireland, Cork, Ireland
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  • For correspondence: ines.thiele@nuigalway.ie
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Abstract

The human microbiome influences the efficacy and safety of a wide variety of commonly prescribed drugs, yet comprehensive systems-level approaches to interrogate drug-microbiome interactions are lacking. Here, we present a computational resource of human microbial genome-scale reconstructions, deemed AGORA2, which accounts for 7,206 strains, includes microbial drug degradation and biotransformation, and was extensively curated based on comparative genomics and literature searches. AGORA2 serves as a knowledge base for the human microbiome and as a metabolic modelling resource. We demonstrate the latter by mechanistically modelling microbial drug metabolism capabilities in single strains and pairwise models. Moreover, we predict the individual-specific drug conversion potential in a cohort of 616 colorectal cancer patients and controls. This analysis reveals that some drug activation capabilities are present in only a subset of individuals, moreover, drug conversion potential correlate with clinical parameters. Thus, AGORA2 paves the way towards personalised, predictive analysis of host-drug-microbiome interactions.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted November 10, 2020.
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AGORA2: Large scale reconstruction of the microbiome highlights wide-spread drug-metabolising capacities
Almut Heinken, Geeta Acharya, Dmitry A. Ravcheev, Johannes Hertel, Malgorzata Nyga, Onyedika Emmanuel Okpala, Marcus Hogan, Stefanía Magnúsdóttir, Filippo Martinelli, German Preciat, Janaka N. Edirisinghe, Christopher S. Henry, Ronan M.T. Fleming, Ines Thiele
bioRxiv 2020.11.09.375451; doi: https://doi.org/10.1101/2020.11.09.375451
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AGORA2: Large scale reconstruction of the microbiome highlights wide-spread drug-metabolising capacities
Almut Heinken, Geeta Acharya, Dmitry A. Ravcheev, Johannes Hertel, Malgorzata Nyga, Onyedika Emmanuel Okpala, Marcus Hogan, Stefanía Magnúsdóttir, Filippo Martinelli, German Preciat, Janaka N. Edirisinghe, Christopher S. Henry, Ronan M.T. Fleming, Ines Thiele
bioRxiv 2020.11.09.375451; doi: https://doi.org/10.1101/2020.11.09.375451

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