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Metabolomics of pulmonary exacerbations reveals the personalized nature of cystic fibrosis disease
Background. Cystic fibrosis (CF) is a genetic disease that results in chronic infections of the lungs. CF patients experience intermittent pulmonary exacerbations (CFPE) that are associated with poor clinical outcomes. CFPE involves an increase in disease symptoms requiring more aggressive therapy....
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
PeerJ Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991883/ https://www.ncbi.nlm.nih.gov/pubmed/27602256 http://dx.doi.org/10.7717/peerj.2174 |
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author | Quinn, Robert A. Lim, Yan Wei Mak, Tytus D. Whiteson, Katrine Furlan, Mike Conrad, Douglas Rohwer, Forest Dorrestein, Pieter |
author_facet | Quinn, Robert A. Lim, Yan Wei Mak, Tytus D. Whiteson, Katrine Furlan, Mike Conrad, Douglas Rohwer, Forest Dorrestein, Pieter |
author_sort | Quinn, Robert A. |
collection | PubMed |
description | Background. Cystic fibrosis (CF) is a genetic disease that results in chronic infections of the lungs. CF patients experience intermittent pulmonary exacerbations (CFPE) that are associated with poor clinical outcomes. CFPE involves an increase in disease symptoms requiring more aggressive therapy. Methods. Longitudinal sputum samples were collected from 11 patients (n = 44 samples) to assess the effect of exacerbations on the sputum metabolome using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The data was analyzed with MS/MS molecular networking and multivariate statistics. Results. The individual patient source had a larger influence on the metabolome of sputum than the clinical state (exacerbation, treatment, post-treatment, or stable). Of the 4,369 metabolites detected, 12% were unique to CFPE samples; however, the only known metabolites significantly elevated at exacerbation across the dataset were platelet activating factor (PAF) and a related monacylglycerophosphocholine lipid. Due to the personalized nature of the sputum metabolome, a single patient was followed for 4.2 years (capturing four separate exacerbation events) as a case study for the detection of personalized biomarkers with metabolomics. PAF and related lipids were significantly elevated during CFPEs of this patient and ceramide was elevated during CFPE treatment. Correlating the abundance of bacterial 16S rRNA gene amplicons to metabolomics data from the same samples during a CFPE demonstrated that antibiotics were positively correlated to Stenotrophomonas and Pseudomonas, while ceramides and other lipids were correlated with Streptococcus, Rothia, and anaerobes. Conclusions. This study identified PAF and other inflammatory lipids as potential biomarkers of CFPE, but overall, the metabolome of CF sputum was patient specific, supporting a personalized approach to molecular detection of CFPE onset. |
format | Online Article Text |
id | pubmed-4991883 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | PeerJ Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-49918832016-09-06 Metabolomics of pulmonary exacerbations reveals the personalized nature of cystic fibrosis disease Quinn, Robert A. Lim, Yan Wei Mak, Tytus D. Whiteson, Katrine Furlan, Mike Conrad, Douglas Rohwer, Forest Dorrestein, Pieter PeerJ Bioinformatics Background. Cystic fibrosis (CF) is a genetic disease that results in chronic infections of the lungs. CF patients experience intermittent pulmonary exacerbations (CFPE) that are associated with poor clinical outcomes. CFPE involves an increase in disease symptoms requiring more aggressive therapy. Methods. Longitudinal sputum samples were collected from 11 patients (n = 44 samples) to assess the effect of exacerbations on the sputum metabolome using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The data was analyzed with MS/MS molecular networking and multivariate statistics. Results. The individual patient source had a larger influence on the metabolome of sputum than the clinical state (exacerbation, treatment, post-treatment, or stable). Of the 4,369 metabolites detected, 12% were unique to CFPE samples; however, the only known metabolites significantly elevated at exacerbation across the dataset were platelet activating factor (PAF) and a related monacylglycerophosphocholine lipid. Due to the personalized nature of the sputum metabolome, a single patient was followed for 4.2 years (capturing four separate exacerbation events) as a case study for the detection of personalized biomarkers with metabolomics. PAF and related lipids were significantly elevated during CFPEs of this patient and ceramide was elevated during CFPE treatment. Correlating the abundance of bacterial 16S rRNA gene amplicons to metabolomics data from the same samples during a CFPE demonstrated that antibiotics were positively correlated to Stenotrophomonas and Pseudomonas, while ceramides and other lipids were correlated with Streptococcus, Rothia, and anaerobes. Conclusions. This study identified PAF and other inflammatory lipids as potential biomarkers of CFPE, but overall, the metabolome of CF sputum was patient specific, supporting a personalized approach to molecular detection of CFPE onset. PeerJ Inc. 2016-08-11 /pmc/articles/PMC4991883/ /pubmed/27602256 http://dx.doi.org/10.7717/peerj.2174 Text en ©2016 Quinn et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. |
spellingShingle | Bioinformatics Quinn, Robert A. Lim, Yan Wei Mak, Tytus D. Whiteson, Katrine Furlan, Mike Conrad, Douglas Rohwer, Forest Dorrestein, Pieter Metabolomics of pulmonary exacerbations reveals the personalized nature of cystic fibrosis disease |
title | Metabolomics of pulmonary exacerbations reveals the personalized nature of cystic fibrosis disease |
title_full | Metabolomics of pulmonary exacerbations reveals the personalized nature of cystic fibrosis disease |
title_fullStr | Metabolomics of pulmonary exacerbations reveals the personalized nature of cystic fibrosis disease |
title_full_unstemmed | Metabolomics of pulmonary exacerbations reveals the personalized nature of cystic fibrosis disease |
title_short | Metabolomics of pulmonary exacerbations reveals the personalized nature of cystic fibrosis disease |
title_sort | metabolomics of pulmonary exacerbations reveals the personalized nature of cystic fibrosis disease |
topic | Bioinformatics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991883/ https://www.ncbi.nlm.nih.gov/pubmed/27602256 http://dx.doi.org/10.7717/peerj.2174 |
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