학술논문
Genome-scale metabolic reconstruction of 7,302 human microorganisms for personalized medicine.
Document Type
Academic Journal
Author
Heinken A; School of Medicine, University of Galway, Galway, Ireland.; Ryan Institute, University of Galway, Galway, Ireland.; INSERM UMRS 1256, Nutrition, Genetics, and Environmental Risk Exposure (NGERE), University of Lorraine, Nancy, France.; Hertel J; School of Medicine, University of Galway, Galway, Ireland.; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.; Acharya G; Integrated BioBank of Luxembourg, Dudelange, Luxembourg.; Ravcheev DA; School of Medicine, University of Galway, Galway, Ireland.; Ryan Institute, University of Galway, Galway, Ireland.; Nyga M; University of Luxembourg, Esch-sur-Alzette, Luxembourg.; Okpala OE; Czech University of Life Sciences Prague, Prague, Czech Republic.; Hogan M; School of Medicine, University of Galway, Galway, Ireland.; Ryan Institute, University of Galway, Galway, Ireland.; Magnúsdóttir S; Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.; Martinelli F; School of Medicine, University of Galway, Galway, Ireland.; Ryan Institute, University of Galway, Galway, Ireland.; Nap B; School of Medicine, University of Galway, Galway, Ireland.; Ryan Institute, University of Galway, Galway, Ireland.; Preciat G; Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands.; Edirisinghe JN; Computation Institute, University of Chicago, Chicago, IL, USA.; Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, IL, USA.; Henry CS; Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, IL, USA.; Fleming RMT; School of Medicine, University of Galway, Galway, Ireland.; Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands.; Thiele I; School of Medicine, University of Galway, Galway, Ireland. ines.thiele@universityofgalway.ie.; Ryan Institute, University of Galway, Galway, Ireland. ines.thiele@universityofgalway.ie.; Division of Microbiology, University of Galway, Galway, Ireland. ines.thiele@universityofgalway.ie.; APC Microbiome Ireland, Cork, Ireland. ines.thiele@universityofgalway.ie.
Source
Publisher: Nature America Publishing Country of Publication: United States NLM ID: 9604648 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1696 (Electronic) Linking ISSN: 10870156 NLM ISO Abbreviation: Nat Biotechnol Subsets: MEDLINE
Subject
Language
English
Abstract
The human microbiome influences the efficacy and safety of a wide variety of commonly prescribed drugs. Designing precision medicine approaches that incorporate microbial metabolism would require strain- and molecule-resolved, scalable computational modeling. Here, we extend our previous resource of genome-scale metabolic reconstructions of human gut microorganisms with a greatly expanded version. AGORA2 (assembly of gut organisms through reconstruction and analysis, version 2) accounts for 7,302 strains, includes strain-resolved drug degradation and biotransformation capabilities for 98 drugs, and was extensively curated based on comparative genomics and literature searches. The microbial reconstructions performed very well against three independently assembled experimental datasets with an accuracy of 0.72 to 0.84, surpassing other reconstruction resources and predicted known microbial drug transformations with an accuracy of 0.81. We demonstrate that AGORA2 enables personalized, strain-resolved modeling by predicting the drug conversion potential of the gut microbiomes from 616 patients with colorectal cancer and controls, which greatly varied between individuals and correlated with age, sex, body mass index and disease stages. AGORA2 serves as a knowledge base for the human microbiome and paves the way to personalized, predictive analysis of host-microbiome metabolic interactions.
(© 2023. The Author(s).)
(© 2023. The Author(s).)