Jörg Stelling | Workshop Two for a Tango - 2nd Edition

Описание: Workshop Metabolism and mathematical models: Two for a tango | 2nd Edition
November 25-26, 2022 | ONLINE WORKSHOP

Jörg Stelling (ETH Zürich, Switzerland)

Title talk: Model-based analysis of microbial communities.

Short abstract: Microbial community analyses with genome-scale metabolic networks (GSMs) are relevant for many application areas, such as the analysis of the human microbiome. Many of such simulations rely on assumptions about the culturing environment, affecting if the culture may reach a metabolically stationary state with constant microbial concentrations. They also require assumptions on decision-making by the microbes: metabolic strategies can be in the interest of individual community members or of the whole community. Here, we present two approaches to address these aspects of community modeling, either by exploring the whole space of possible community interactions, or by making environment and decision making explicit. First, in the realm of metabolic pathway analysis, we define the minimal pathways (MPs) of a metabolic (sub)network as a subset of its elementary flux vectors. We enumerate or sample them efficiently by iterative minimization and a simple graph representation of MPs. Enumerating all minimal exchanges in a host-microbe model of the human gut predicts exchanges of metabolites associated with host-microbiota homeostasis and human health. Second, we investigate four combinations of assumptions on environment representation and decision-making, and provide novel mathematical formulations for community simulation. Our results stress that different assumption combinations give qualitatively different predictions on microbial coexistence by differential substrate utilization. Both approaches suggest that fundamental mechanisms of community interactions are under-explored in current GSM-based analysis with its strong focus on coexistence states due to division of labor.

This workshop was organised in the context of two projects, both with the Inria European Team Erable. One of the projects involves a partnership with the University of São Paulo (USP), in São Paulo, Brazil, more specifically the Institute of Mathematics and Statistics (IME) and the Institute of Biomedical Sciences – Inria Associated Team Capoeira – and the other involves the INESC-ID/IST in Portugal, ETH in Zürich and EMBL in Heidelberg – H2020 Twinning Project OLISSIPO.