RT Journal Article
SR Electronic
T1 AGORA2: Large scale reconstruction of the microbiome highlights wide-spread drug-metabolising capacities
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.11.09.375451
DO 10.1101/2020.11.09.375451
A1 Almut Heinken
A1 Geeta Acharya
A1 Dmitry A. Ravcheev
A1 Johannes Hertel
A1 Malgorzata Nyga
A1 Onyedika Emmanuel Okpala
A1 Marcus Hogan
A1 Stefanía Magnúsdóttir
A1 Filippo Martinelli
A1 German Preciat
A1 Janaka N. Edirisinghe
A1 Christopher S. Henry
A1 Ronan M.T. Fleming
A1 Ines Thiele
YR 2020
UL http://biorxiv.org/content/early/2020/11/10/2020.11.09.375451.abstract
AB 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 StatementThe authors have declared no competing interest.