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Zero-inflated generalized Dirichlet multinomial regression model for microbiome compositional data analysis.

ABSTRACT: There is heightened interest in using high-throughput sequencing technologies to quantify abundances of microbial taxa and linking the abundance to human diseases and traits. Proper modeling of multivariate taxon counts is essential to the power of detecting this association. Existing models are limited in handling excessive zero observations in taxon counts and in flexibly accommodating complex correlation structures and dispersion patterns among taxa. In this article, we develop a new probability distribution, zero-inflated generalized Dirichlet multinomial (ZIGDM), that overcomes these limitations in modeling multivariate taxon counts. Based on this distribution, we propose a ZIGDM regression model to link microbial abundances to covariates (e.g. disease status) and develop a fast expectation-maximization algorithm to efficiently estimate parameters in the model. The derived tests enable us to reveal rich patterns of variation in microbial compositions including differential mean and dispersion. The advantages of the proposed methods are demonstrated through simulation studies and an analysis of a gut microbiome dataset.

SUBMITTER: Tang ZZ

PROVIDER: S-EPMC7410344 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and aimsWe analyze the possible predictive variables for Adverse Events (AEs) during sedation for gastrointestinal (GI) endoscopy.MethodsWe consider 23,788 GI endoscopies under sedation on adults between 2012 and 2019. A Zero-Inflated Poisson Regression Mixture (ZIPRM) model for count data with concomitant variables is applied, accounting for unobserved heterogeneity and evaluating the risks of multi-drug sedation. A multinomial logit model is also estimated to evaluate cardiovascular, respiratory, hemorrhagic, other AEs and stopping the procedure risk factors.ResultsIn 7.55% of cases, one or more AEs occurred, most frequently cardiovascular (3.26%) or respiratory (2.77%). Our ZIPRM model identifies one population for non-zero counts. The AE-group reveals that age >75 years yields 46% more AEs than age <66 years; Body Mass Index (BMI) ≥27 27% more AEs than BMI <21; emergency 11% more AEs than routine. Any one-point increment in the American Society of Anesthesiologists (ASA) score and the Mallampati score determines respectively a 42% and a 16% increment in AEs; every hour prolonging endoscopy increases AEs by 41%. Regarding sedation with propofol alone (the sedative of choice), adding opioids to propofol increases AEs by 43% and adding benzodiazepines by 51%. Cardiovascular AEs are increased by age, ASA score, smoke, in-hospital, procedure duration, midazolam/fentanyl associated with propofol. Respiratory AEs are increased by BMI, ASA and Mallampati scores, emergency, in-hospital, procedure duration, midazolam/fentanyl associated with propofol. Hemorrhagic AEs are increased by age, in-hospital, procedure duration, midazolam/fentanyl associated with propofol. The risk of suspension of the endoscopic procedure before accomplishment is increased by female gender, ASA and Mallampati scores, and in-hospital, and it is reduced by emergency and procedure duration.ConclusionsAge, BMI, ASA score, Mallampati score, in-hospital, procedure duration, other sedatives with propofol increase the risk for AEs during sedation for GI endoscopy.

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Zero-inflated generalized Dirichlet multinomial regression model for microbiome compositional data analysis.

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