Capturing the dynamics of microbiomes using individual-specific networks

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

Abstract Background Longitudinal analysis of multivariate individual-specific microbiome profiles over time or across conditions remains a daunting task. The vast majority of statistical tools and methods available to study the microbiota are based upon cross-sectional data. Over the past few years, several attempts have been made to model the dynamics of bacterial species over time or across conditions. However, the field needs novel views on how to incorporate individual-specific microbial associations in temporal analyses when the focus lies on microbial interactions. Results Here, we propose a novel data analysis framework, called MNDA, to uncover taxon neighbourhood dynamics that combines representation learning and individual-specific microbiome co-occurrence networks. We show that tracking local neighbourhood dynamics in microbiome interaction or co-occurrence networks can yield complementary information to standard approaches that only use microbial abundances or pairwise microbial interactions. We use cohort data on infants for whom microbiome data was available at 6 and 9 months after birth, as well as information on mode of delivery and diet changes over time. In particular, MNDA-based prediction models outperform traditional prediction models based on individual-specific abundances, and enable the detection of microbes whose neighbourhood dynamics are informative of clinical variables. We further show that similarity analyses of individuals based on microbial neighbourhood dynamics can be used to find subpopulations of individuals with potential relevance to clinical practice. The annotated source code for the MNDA framework can be downloaded from: https://github.com/H2020TranSYS/microbiome_dynamics Conclusions MNDA extracts information from matched microbiome profiles and opens new avenues to personalized prediction or stratified medicine with temporal microbiome data.

Authors 8

1. Behnam Yousefi

   Institut Pasteur · Université Paris Cité · Sorbonne Université · KU Leuven

   Affiliation as printed

   BIO3 – Laboratory for Systems Medicine, KU Leuven

   BIO3 – Laboratory for Systems Medicine, KU Leuven, Leuven, Belgium

   Computational Systems Biomedicine Lab, Institut Pasteur, Université Paris Cité

   Computational Systems Biomedicine Lab, Institut Pasteur, Université Paris Cité, Paris, France

   École Doctorale Complexite du vivant, Sorbonne Universite

   École Doctorale Complexite du vivant, Sorbonne Universite, 75005 Paris, France

   BIO – Laboratory for Systems Medicine, KU Leuven, Leuven, Belgium

2. Federico Melograna

   KU Leuven

   Affiliation as printed

   BIO3 – Laboratory for Systems Medicine, KU Leuven

   BIO3 – Laboratory for Systems Medicine, KU Leuven, Leuven, Belgium

   BIO – Laboratory for Systems Medicine, KU Leuven, Leuven, Belgium

3. Gianluca Galazzo

   Maastricht University Medical Centre · Maastricht University

   Affiliation as printed

   School of Nutrition and Translational Research in Metabolism (NUTRIM), Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Maastricht University Medical Center+

   School of Nutrition and Translational Research in Metabolism (NUTRIM), Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Maastricht University Medical Center+, Maastricht, The Netherlands

4. Niels van Best Aachen Institute of Medical Microbiology

   Maastricht University Medical Centre · Maastricht University · Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute of Medical Microbiology, RWTH University Hospital Aachen, RWTH University

   Institute of Medical Microbiology, RWTH University Hospital Aachen, RWTH University, Aachen, Germany

   School of Nutrition and Translational Research in Metabolism (NUTRIM), Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Maastricht University Medical Center+

   School of Nutrition and Translational Research in Metabolism (NUTRIM), Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Maastricht University Medical Center+, Maastricht, The Netherlands

5. Monique Mommers

   Maastricht University · Care and Public Health Research Institute

   Affiliation as printed

   Department of Epidemiology, Care and Public Health Research Institute (CAPHRI), Maastricht University

   Department of Epidemiology, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands

6. John Penders

   Maastricht University Medical Centre · Maastricht University · Care and Public Health Research Institute

   Affiliation as printed

   Care and Public Health Research Institute (CAPHRI), Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Maastricht University Medical Center+

   Care and Public Health Research Institute (CAPHRI), Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Maastricht University Medical Center+, Maastricht, The Netherlands

   Department of Epidemiology, Care and Public Health Research Institute (CAPHRI), Maastricht University

   Department of Epidemiology, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands

7. Benno Schwikowski

   Institut Pasteur · Université Paris Cité

   Affiliation as printed

   Computational Systems Biomedicine Lab, Institut Pasteur, Université Paris Cité

   Computational Systems Biomedicine Lab, Institut Pasteur, Université Paris Cité, Paris, France

8. Kristel Van Steen corresponding

   University of Liège · KU Leuven

   Affiliation as printed

   BIO3 – Laboratory for Systems Genetics, GIGA-R Medical Genomics, University of Liège

   BIO3 – Laboratory for Systems Genetics, GIGA-R Medical Genomics, University of Liège, Liège, Belgium

   BIO3 – Laboratory for Systems Medicine, KU Leuven

   BIO3 – Laboratory for Systems Medicine, KU Leuven, Leuven, Belgium

   BIO – Laboratory for Systems Medicine, KU Leuven, Leuven, Belgium