Different functional genes of upper airway microbiome associated with natural course of childhood asthma

Kim, Bong Soo; Lee, Eun; Lee, Min‐Jung; Kang, Mi‐Jin; Yoon, Jisun; Cho, Hyun Ju; Park, Jaehyun; Won, Sungho; Lee, So Yeon; Hong, Soo‐Jong

doi:10.1111/all.13331

Cited by 42 publications

(37 citation statements)

References 49 publications

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“…But the opposite is not true. This supports the previous studies that Parvimonas abundance changed in subjects with pulmonary disease (e.g., asthma or COPD) comparing to the control group (Pragman et al, 2012;Kim et al, 2017). However, either Prevotella or Porphyromonas lost its significance when adjusting for the other.…”

Section: Simulation Resultssupporting

confidence: 90%

Exact Tests of Zero Variance Component in Presence of Multiple Variance Components with Application to Longitudinal Microbiome Study

Zhai

Knox²,

Twigg

et al. 2018

Preprint

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Summary:In the metagenomics studies, testing the association of microbiome composition and clinical conditions translates to testing the nullity of variance components. Computationally efficient score tests have been the major tools. But they can only apply to the null hypothesis with a single variance component and when sample sizes are large. Therefore, they are not applicable to longitudinal microbiome studies. In this paper, we propose exact tests (score test, likelihood ratio test, and restricted likelihood ratio test) to solve the problems of (1) testing the association of the overall microbiome composition in a longitudinal design and (2) detecting the association of one specific microbiome cluster while adjusting for the effects from related clusters. Our approach combines the exact tests for null hypothesis with a single variance component with a strategy of reducing multiple variance components to a single one. Simulation studies demonstrate that our method has correct type I error rate and superior power compared to existing methods at small sample sizes and weak signals. Finally, we apply our method to a longitudinal pulmonary microbiome study of human immunodeficiency virus (HIV) infected patients and reveal two interesting genera Prevotella and Veillonella associated with forced vital capacity. Our findings shed lights on the impact of All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

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Section: Simulation Resultssupporting

confidence: 90%

Exact Tests of Zero Variance Component in Presence of Multiple Variance Components with Application to Longitudinal Microbiome Study

Zhai

Knox²,

Twigg

et al. 2018

Preprint

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show abstract

“…But the opposite is not true. This supports the findings of the previous studies that Parvimonas abundance changed in subjects with pulmonary disease (e.g., asthma or COPD) compared to the control group (Kim et al, 2018;Pragman, Kim, Reilly, Wendt, & Isaacson, 2012). However, either Prevotella or Porphyromonas lost its significance when adjusting for the other.…”

Section: Analysis Of Longitudinal Pulmonary Microbiome Datasupporting

confidence: 91%

“…The missing covariate is imputed by its mean. This supports the findings of the previous studies that Parvimonas abundance changed in subjects with pulmonary disease (e.g., asthma or COPD) compared to the control group (Kim et al, 2018;Pragman, Kim, Reilly, Wendt, & Isaacson, 2012). However at the phylum level, Bacteroidetes shows a significant association with spirometry while Firmicutes shows a significant association with diffusing capacity measures.…”

Section: Analysis Of Longitudinal Pulmonary Microbiome Datasupporting

confidence: 90%

Exact variance component tests for longitudinal microbiome studies

Zhai

Knox

Twigg

et al. 2019

Genetic Epidemiology

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In metagenomic studies, testing the association between microbiome composition and clinical outcomes translates to testing the nullity of variance components. Motivated by a lung human immunodeficiency virus (HIV) microbiome project, we study longitudinal microbiome data by using variance component models with more than two variance components. Current testing strategies only apply to models with exactly two variance components and when sample sizes are large. Therefore, they are not applicable to longitudinal microbiome studies. In this paper, we propose exact tests (score test, likelihood ratio test, and restricted likelihood ratio test) to (a) test the association of the overall microbiome composition in a longitudinal design and (b) detect the association of one specific microbiome cluster while adjusting for the effects from related clusters. Our approach combines the exact tests for null hypothesis with a single variance component with a strategy of reducing multiple variance components to a single one. Simulation studies demonstrate that our method has a correct type I error rate and superior power compared to existing methods at small sample sizes and weak signals. Finally, we apply our method to a longitudinal pulmonary microbiome study of HIV‐infected patients and reveal two interesting genera Prevotella and Veillonella associated with forced vital capacity. Our findings shed light on the impact of the lung microbiome on HIV complexities. The method is implemented in the open‐source, high‐performance computing language Julia and is freely available at https://github.com/JingZhai63/VCmicrobiome.

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“…A systematic review and meta‐analysis indicates that the intake of vitamin D during pregnancy, as measured from 25‐hydroxyvitamin D levels, is associated with a reduction in the offspring's respiratory tract infections but there is no supporting evidence on a beneficial effect on asthma or allergies . The airway microbiota composition in children is different in healthy, asthmatic, and remission groups . The severity of bronchial hyperresponsiveness is associated with the presence of specific bacteria, upregulation of inflammatory genes, and lack of anti‐inflammatory prostaglandin E2 genes in the airway microbiome of asthmatic children.…”

Section: Prediction and Prevention Of Allergic Diseasementioning

confidence: 99%

“…54 The airway microbiota composition in children is different in healthy, asthmatic, and remission groups. 55 The severity of bronchial hyperresponsiveness is associated with the presence of specific bacteria, upregulation of inflammatory genes, and lack of anti-inflammatory prostaglandin E2 genes in the airway microbiome of asthmatic children. A three-generational cohort study has recently shown that children whose maternal grandmother smoked during pregnancy are at higher risk of developing early persistent childhood asthma.…”

Section: Pred Ic Ti On and Pre Venti On Of Allerg I C D Is E A S Ementioning

confidence: 99%

Highlights and recent developments in airway diseases in EAACI journals (2018)

Bousquet

Akdiş

Grattan

et al. 2019

Allergy

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The European Academy of Allergy and Clinical Immunology (EAACI) supports three journals: Allergy, Pediatric Allergy and Immunology, and Clinical and Translational Allergy. EAACI's major goals include supporting the promotion of health, in which the prevention of allergy and asthma plays a critical role, and disseminating the knowledge of allergic disease to all stakeholders. In 2018, the remarkable progress in the identification of basic mechanisms of allergic and respiratory diseases as well as the translation of these findings into clinical practice were observed. Last year's highlights include publication of EAACI guidelines for allergen immunotherapy, many EAACI Position Papers covering important aspects for the specialty, better understanding of molecular and cellular mechanisms, identification of biomarkers for disease prediction and progress monitoring, novel prevention and intervention studies, elucidation of mechanisms of multimorbidities, introduction of new drugs to the clinics, recently completed phase three clinical studies, and publication of a large number of allergen immunotherapy studies and meta‐analyses.

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Different functional genes of upper airway microbiome associated with natural course of childhood asthma

Abstract: These data suggest that alterations in the composition and function of the upper airway microbiome could be related with the natural course of asthma in children.

Cited by 42 publications

References 49 publications

Exact Tests of Zero Variance Component in Presence of Multiple Variance Components with Application to Longitudinal Microbiome Study

Exact Tests of Zero Variance Component in Presence of Multiple Variance Components with Application to Longitudinal Microbiome Study

Exact variance component tests for longitudinal microbiome studies

Highlights and recent developments in airway diseases in EAACI journals (2018)

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