Abstract

MotivationRecent microbiome dynamics studies highlight the current inability to predict the effects of external perturbations on complex microbial populations. To do so would be particularly advantageous in fields such as medicine, bioremediation or industrial scenarios.ResultsMDPbiome statistically models longitudinal metagenomics samples undergoing perturbations as a Markov Decision Process (MDP). Given a starting microbial composition, our MDPbiome system suggests the sequence of external perturbation(s) that will engineer that microbiome to a goal state, for example, a healthier or more performant composition. It also estimates intermediate microbiome states along the path, thus making it possible to avoid particularly undesirable/unhealthy states. We demonstrate MDPbiome performance over three real and distinct datasets, proving its flexibility, and the reliability and universality of its output ‘optimal perturbation policy’. For example, an MDP created using a vaginal microbiome time series, with a goal of recovering from bacterial vaginosis, suggested avoidance of perturbations such as lubricants or sex toys; while another MDP provided a quantitative explanation for why salmonella vaccine accelerates gut microbiome maturation in chicks. This novel analytical approach has clear applications in medicine, where it could suggest low-impact clinical interventions that will lead to achievement or maintenance of a healthy microbial population, or alternately, the sequence of interventions necessary to avoid strongly negative microbiome states.Availability and implementationCode (https://github.com/beatrizgj/MDPbiome) and result files (https://tomdelarosa.shinyapps.io/MDPbiome/) are available online.Supplementary information Supplementary data are available at Bioinformatics online.

Highlights

  • This manuscript addresses an important challenge in microbiome analysis (Bashan et al, 2 d 6 Bradley and Pollard, 2017; Gilbert et al, 2016): precise description of longitudinal microbiome variability and dynamics

  • 2.4.1 Sensitivity analysis on input data We apply a sensitivity analysis on the estimated transition probabilities to measure the stability of the optimal policy, similar to (Chen et al, 2017) but for an indefinite horizon for Markov Decision Process (MDP)

  • MDPbiome builds a model that suggests a 'prescription' of external perturbations that should be applied to a given microbiome that will result in its navigation through a subset of healthy or acceptable states, avoiding disease or other undesirable states, reaching a goal state

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Summary

Introduction

This manuscript addresses an important challenge in microbiome analysis (Bashan et al, 2 d 6 Bradley and Pollard, 2017; Gilbert et al, 2016): precise description of longitudinal microbiome variability and dynamics. It responds to the call for a 'microbial Global Positioning System (GPS)', originally suggested by Gilbert et al (2016), where the start and end states of the microbiome for an individual subject could be defined and located, and the optimal route from start to end clearly mapped. Metagenomics analyses of the same population over time may reveal the detailed dynamics within complex bacterial communities, interactions between microbes and the influence of external perturbations. Inferring microbial dynamics from temporal metagenomics data is, a very challenging task It should be possible to utilize such data to construct models aimed at in silico prediction of perturbation-outcomes

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