Genomic attributes of airway commensal bacteria and mucosa.


Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
12 Feb 2024
Historique:
received: 30 01 2023
accepted: 22 01 2024
medline: 13 2 2024
pubmed: 13 2 2024
entrez: 12 2 2024
Statut: epublish

Résumé

Microbial communities at the airway mucosal barrier are conserved and highly ordered, in likelihood reflecting co-evolution with human host factors. Freed of selection to digest nutrients, the airway microbiome underpins cognate management of mucosal immunity and pathogen resistance. We show here the initial results of systematic culture and whole-genome sequencing of the thoracic airway bacteria, identifying 52 novel species amongst 126 organisms that constitute 75% of commensals typically present in heathy individuals. Clinically relevant genes encode antimicrobial synthesis, adhesion and biofilm formation, immune modulation, iron utilisation, nitrous oxide (NO) metabolism and sphingolipid signalling. Using whole-genome content we identify dysbiotic features that may influence asthma and chronic obstructive pulmonary disease. We match isolate gene content to transcripts and metabolites expressed late in airway epithelial differentiation, identifying pathways to sustain host interactions with microbiota. Our results provide a systematic basis for decrypting interactions between commensals, pathogens, and mucosa in lung diseases of global significance.

Identifiants

pubmed: 38347162
doi: 10.1038/s42003-024-05840-3
pii: 10.1038/s42003-024-05840-3
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

171

Subventions

Organisme : Wellcome Trust (Wellcome)
ID : WT098051; WT206194 and 108413/A/15/D
Organisme : Wellcome Trust (Wellcome)
ID : 215359/Z/19/Z
Organisme : Wellcome Trust (Wellcome)
ID : WT096964MA and WT097117MA
Organisme : Office of Science, Government of Western Australia
ID : Busselton Healthy Ageing Study

Informations de copyright

© 2024. The Author(s).

Références

Adams, W. C., Measurement of breathing rate and volume in routinely performed daily activities. California Environmental protection agency, California Air Resources Board contract no. A033–A205 (1993).
Weibel, E. R. & Gomez, D. M. Architecture of the human lung. Use of quantitative methods establishes fundamental relations between size and number of lung structures. Science 137, 577–585 (1962).
pubmed: 14005590 doi: 10.1126/science.137.3530.577
Hasleton, P. S. The internal surface area of the adult human lung. J. Anat. 112, 391–400 (1972).
pubmed: 4564685 pmcid: 1271180
Ferkol, T. & Schraufnagel, D. The global burden of respiratory disease. Ann. Am. Thorac. Soc. 11, 404–406 (2014).
pubmed: 24673696 doi: 10.1513/AnnalsATS.201311-405PS
Cookson, W., Moffatt, M., Rapeport, G. & Quint, J. A pandemic lesson for global lung diseases: exacerbations are preventable. Am. J. Respir. Crit. Care Med. 205, 1271–1280 (2022).
Singanayagam, A. et al. Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: a prospective, longitudinal, cohort study. Lancet Infect. Dis. 22, 183–195 (2022).
pubmed: 34756186 pmcid: 8554486 doi: 10.1016/S1473-3099(21)00648-4
Killingley, B. et al. Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults. Nat. Med. 28, 1031–41 (2022).
Hilty, M. et al. Disordered microbial communities in asthmatic airways. PLoS ONE 5, e8578 (2010).
pubmed: 20052417 pmcid: 2798952 doi: 10.1371/journal.pone.0008578
Man, W. H., de Steenhuijsen Piters, W. A. & Bogaert, D. The microbiota of the respiratory tract: gatekeeper to respiratory health. Nat. Rev. Microbiol. 15, 259–270 (2017).
pubmed: 28316330 pmcid: 7097736 doi: 10.1038/nrmicro.2017.14
Ichinohe, T. et al. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc. Natl Acad. Sci. USA 108, 5354–5359 (2011).
pubmed: 21402903 pmcid: 3069176 doi: 10.1073/pnas.1019378108
Brown, R. L., Sequeira, R. P. & Clarke, T. B. The microbiota protects against respiratory infection via GM-CSF signaling. Nat. Commun. 8, 1512 (2017).
pubmed: 29142211 pmcid: 5688119 doi: 10.1038/s41467-017-01803-x
Yang, D. et al. Many chemokines including CCL20/MIP-3alpha display antimicrobial activity. J. Leukoc. Biol. 74, 448–455 (2003).
pubmed: 12949249 doi: 10.1189/jlb.0103024
de Steenhuijsen Piters, W. A. A. et al. Early-life viral infections are associated with disadvantageous immune and microbiota profiles and recurrent respiratory infections. Nat. Microbiol 7, 224–237 (2022).
pubmed: 35058634 doi: 10.1038/s41564-021-01043-2
Comer, D. M., Elborn, J. S. & Ennis, M. Comparison of nasal and bronchial epithelial cells obtained from patients with COPD. PLoS ONE 7, e32924 (2012).
pubmed: 22412951 pmcid: 3295776 doi: 10.1371/journal.pone.0032924
Stearns, J. C. et al. Culture and molecular-based profiles show shifts in bacterial communities of the upper respiratory tract that occur with age. ISME J. 9, 1246–1259 (2015).
pubmed: 25575312 pmcid: 4409167 doi: 10.1038/ismej.2014.250
Charlson, E. S. et al. Topographical continuity of bacterial populations in the healthy human respiratory tract. Am. J. Respir. Crit. Care Med 184, 957–963 (2011).
pubmed: 21680950 pmcid: 3208663 doi: 10.1164/rccm.201104-0655OC
Dickson, R. P. et al. Spatial variation in the healthy human lung microbiome and the adapted island model of lung biogeography. Ann. Am. Thorac. Soc. 12, 821–830 (2015).
pubmed: 25803243 pmcid: 4590020 doi: 10.1513/AnnalsATS.201501-029OC
Turek, E. M. et al. Airway microbial communities, smoking and asthma in a general population sample. EBioMedicine 71, 103538 (2021).
pubmed: 34425308 pmcid: 8387768 doi: 10.1016/j.ebiom.2021.103538
Cookson, W. O. C. M., Cox, M. J. & Moffatt, M. F. New opportunities for managing acute and chronic lung infections. Nat. Rev. Microbiol. 16, 111–120 (2018).
pubmed: 29062070 doi: 10.1038/nrmicro.2017.122
Campbell, C. D., Barnett, C. & Sulaiman, I. A clinicians’ review of the respiratory microbiome. Breathe (Sheff.) 18, 210161 (2022).
pubmed: 36338247 doi: 10.1183/20734735.0161-2021
Jansen, R. R. et al. Frequent detection of respiratory viruses without symptoms: toward defining clinically relevant cutoff values. J. Clin. Microbiol. 49, 2631–2636 (2011).
pubmed: 21543571 pmcid: 3147826 doi: 10.1128/JCM.02094-10
Cuthbertson, L. et al. The fungal airway microbiome in cystic fibrosis and non-cystic fibrosis bronchiectasis. J. Cyst. Fibros. 20, 295–302 (2021).
pubmed: 32540174 pmcid: 8048771 doi: 10.1016/j.jcf.2020.05.013
McBrien, C. N. Doctor of Philosophy (PhD) (Imperial College London, 2020).
Rodriguez, R, L. et al. The Microbial Genomes Atlas (MiGA) webserver: taxonomic and gene diversity analysis of Archaea and Bacteria at the whole genome level. Nucleic Acids Res. 46, W282–w288 (2018).
doi: 10.1093/nar/gky467
Dupont, C. L. et al. Genomic insights to SAR86, an abundant and uncultivated marine bacterial lineage. ISME J. 6, 1186–1199 (2012).
pubmed: 22170421 doi: 10.1038/ismej.2011.189
Mende, D. R. et al. proGenomes2: an improved database for accurate and consistent habitat, taxonomic and functional annotations of prokaryotic genomes. Nucleic Acids Res. 48, D621–d625 (2020).
pubmed: 31647096
Langfelder, P., Zhang, B. & Horvath, S. Defining clusters from a hierarchical cluster tree: the Dynamic Tree Cut package for R. Bioinformatics 24, 719–720 (2007).
pubmed: 18024473 doi: 10.1093/bioinformatics/btm563
Palmer, J. D. & Foster, K. R. Bacterial species rarely work together. Science 376, 581–582 (2022).
pubmed: 35511986 doi: 10.1126/science.abn5093
Lucas, R. et al. Impact of bacterial toxins in the lungs. Toxins (Basel) 12, 223 (2020).
pubmed: 32252376 doi: 10.3390/toxins12040223
Mikhailik, A. et al. nNOS regulates ciliated cell polarity, ciliary beat frequency, and directional flow in mouse trachea. Life Sci. Alliance 4, e202000981 (2021).
pubmed: 33653689 pmcid: 8008965 doi: 10.26508/lsa.202000981
De Groote, M. A. & Fang, F. C. NO inhibitions: antimicrobial properties of nitric oxide. Clin. Infect. Dis. 21, S162–S165 (1995).
pubmed: 8845445 doi: 10.1093/clinids/21.Supplement_2.S162
Cassat, J. E. & Skaar, E. P. Iron in infection and immunity. Cell Host Microbe 13, 509–519 (2013).
pubmed: 23684303 pmcid: 3676888 doi: 10.1016/j.chom.2013.04.010
Whitby, P. W., Seale, T. W., VanWagoner, T. M., Morton, D. J. & Stull, T. L. The iron/heme regulated genes of Haemophilus influenzae: comparative transcriptional profiling as a tool to define the species core modulon. BMC Genomics 10, 6–6 (2009).
pubmed: 19128474 pmcid: 2627913 doi: 10.1186/1471-2164-10-6
Hannun, Y. A. & Obeid, L. M. Principles of bioactive lipid signalling: lessons from sphingolipids. Nat. Rev. Mol. Cell Biol. 9, 139–150 (2008).
pubmed: 18216770 doi: 10.1038/nrm2329
Theken, K. N. & FitzGerald, G. A. Bioactive lipids in antiviral immunity. Science 371, 237–238 (2021).
pubmed: 33446545 doi: 10.1126/science.abf3192
Audi, A., Soudani, N., Dbaibo, G., & Zaraket, H., Depletion of Host and Viral Sphingomyelin Impairs Influenza Virus Infection. Front. Microbiol. 11, 612 (2020).
Solger, F. et al. A Role of Sphingosine in the Intracellular Survival of Neisseria gonorrhoeae. Front. Cell. Infect. Microbiol. 10, 215 (2020).
Moffatt, M. F. et al. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature 448, 470–473 (2007).
pubmed: 17611496 doi: 10.1038/nature06014
Breslow, D. K. et al. Orm family proteins mediate sphingolipid homeostasis. Nature 463, 1048–1053 (2010).
pubmed: 20182505 pmcid: 2877384 doi: 10.1038/nature08787
Caliskan, M. et al. Rhinovirus wheezing illness and genetic risk of childhood-onset asthma. N. Engl. J. Med. 368, 1398–1407 (2013).
pubmed: 23534543 pmcid: 3755952 doi: 10.1056/NEJMoa1211592
Johnson, E. L. et al. Sphingolipids produced by gut bacteria enter host metabolic pathways impacting ceramide levels. Nat. Commun. 11, 2471 (2020).
pubmed: 32424203 pmcid: 7235224 doi: 10.1038/s41467-020-16274-w
Brown, E. M. et al. Bacteroides-Derived Sphingolipids Are Critical for Maintaining Intestinal Homeostasis and Symbiosis. Cell Host Microbe 25, 668–680.e667 (2019).
pubmed: 31071294 pmcid: 6544385 doi: 10.1016/j.chom.2019.04.002
Zheng, Y. et al. Commensal Staphylococcus epidermidis contributes to skin barrier homeostasis by generating protective ceramides. Cell Host Microbe 30, 301–313.e309 (2022).
pubmed: 35123653 pmcid: 8917079 doi: 10.1016/j.chom.2022.01.004
Bousbaine, D. et al. A conserved Bacteroidetes antigen induces anti-inflammatory intestinal T lymphocytes. Science 377, 660–666 (2022).
pubmed: 35926021 pmcid: 9766740 doi: 10.1126/science.abg5645
Lopez Velazquez, M. & Highland, K. B. Pulmonary manifestations of systemic lupus erythematosus and Sjögren’s syndrome. Curr. Opin. Rheumatol. 30, 449–464 (2018).
pubmed: 29985183 doi: 10.1097/BOR.0000000000000531
Sim, S. & Wolin, S. L. Emerging roles for the Ro 60-kDa autoantigen in noncoding RNA metabolism. Wiley Interdiscip. Rev. RNA 2, 686–699 (2011).
pubmed: 21823229 pmcid: 3154076 doi: 10.1002/wrna.85
Greiling, T. M. et al. Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus. Sci. Transl. Med. 10, eaan2306 (2018).
Hosang, L. et al. The lung microbiome regulates brain autoimmunity. Nature 603, 138–144 (2022).
pubmed: 35197636 doi: 10.1038/s41586-022-04427-4
Odoardi, F. et al. T cells become licensed in the lung to enter the central nervous system. Nature 488, 675–679 (2012).
pubmed: 22914092 doi: 10.1038/nature11337
Freije, C. A. et al. Programmable Inhibition and Detection of RNA Viruses Using Cas13. Mol. Cell 76, 826–837.e811 (2019).
pubmed: 31607545 pmcid: 7422627 doi: 10.1016/j.molcel.2019.09.013
Burmistrz, M., Krakowski, K. & Krawczyk-Balska, A. RNA-Targeting CRISPR-Cas Systems and Their Applications. Int. J. Mol. Sci. 21, 1122 (2020).
pubmed: 32046217 pmcid: 7036953 doi: 10.3390/ijms21031122
Větrovský, T. & Baldrian, P. The variability of the 16S rRNA gene in bacterial genomes and its consequences for bacterial community analyses. PLoS ONE 8, e57923 (2013).
pubmed: 23460914 pmcid: 3583900 doi: 10.1371/journal.pone.0057923
Farrell, R. J. & LaMont, J. T. Microbial factors in inflammatory bowel disease. Gastroenterol. Clin. North Am. 31, 41–62 (2002).
pubmed: 12122743 doi: 10.1016/S0889-8553(01)00004-8
Holmes, I., Harris, K. & Quince, C. Dirichlet multinomial mixtures: generative models for microbial metagenomics. PLoS ONE 7, e30126 (2012).
pubmed: 22319561 pmcid: 3272020 doi: 10.1371/journal.pone.0030126
Forslund, S. K. et al. Combinatorial, additive and dose-dependent drug-microbiome associations. Nature 600, 500–505 (2021).
pubmed: 34880489 doi: 10.1038/s41586-021-04177-9
Huang, Y. J. et al. Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma. J. Allergy Clin. Immunol. 127, 372–381 e373 (2011).
pubmed: 21194740 doi: 10.1016/j.jaci.2010.10.048
Langille, M. G. et al. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat. Biotechnol. 31, 814–821 (2013).
pubmed: 23975157 pmcid: 3819121 doi: 10.1038/nbt.2676
Corfield, A. P. Mucins: a biologically relevant glycan barrier in mucosal protection. Biochim. Biophys. Acta (BBA) Gen. Subj. 1850, 236–252 (2015).
doi: 10.1016/j.bbagen.2014.05.003
Deplancke, B. & Gaskins, H. R. Microbial modulation of innate defense: goblet cells and the intestinal mucus layer. Am. J. Clin. Nutr. 73, 1131s–1141s (2001).
pubmed: 11393191 doi: 10.1093/ajcn/73.6.1131S
Horani, A., Ferkol, T. W., Dutcher, S. K. & Brody, S. L. Genetics and biology of primary ciliary dyskinesia. Paediatr. Respir. Rev. 18, 18–24 (2016).
pubmed: 26476603
Coleridge, J. C. & Coleridge, H. M. Afferent vagal C fibre innervation of the lungs and airways and its functional significance. Rev. Physiol. Biochem. Pharm. 99, 1–110 (1984).
Udit, S., Blake, K. & Chiu, I. M. Somatosensory and autonomic neuronal regulation of the immune response. Nat. Rev. Neurosci. 23, 157–171 (2022).
pubmed: 34997214 pmcid: 9539447 doi: 10.1038/s41583-021-00555-4
Barnes, P. J. Neurogenic inflammation in the airways. Respir. Physiol. 125, 145–154 (2001).
pubmed: 11240158 doi: 10.1016/S0034-5687(00)00210-3
Mazzone, S. B. & Undem, B. J. Vagal afferent innervation of the airways in health and disease. Physiol. Rev. 96, 975–1024 (2016).
pubmed: 27279650 pmcid: 4982036 doi: 10.1152/physrev.00039.2015
Chung, K. F. et al. Cough hypersensitivity and chronic cough. Nat. Rev. Dis. Prim. 8, 45 (2022).
pubmed: 35773287 doi: 10.1038/s41572-022-00370-w
Mountoufaris, G. et al. Multicluster Pcdh diversity is required for mouse olfactory neural circuit assembly. Science 356, 411–414 (2017).
pubmed: 28450637 pmcid: 5529182 doi: 10.1126/science.aai8801
Darzi, Y., Letunic, I., Bork, P. & Yamada, T. iPath3.0: interactive pathways explorer v3. Nucleic Acids Res. 46, W510–W513 (2018).
pubmed: 29718427 pmcid: 6031023 doi: 10.1093/nar/gky299
Tunney, M. M. et al. Detection of anaerobic bacteria in high numbers in sputum from patients with cystic fibrosis. Am. J. Respir. Crit. Care Med. 177, 995–1001 (2008).
pubmed: 18263800 doi: 10.1164/rccm.200708-1151OC
Goeteyn, E. et al. Commensal bacteria of the lung microbiota synergistically inhibit inflammation in a three-dimensional epithelial cell model. Front. Immunol. 14, 1176044 (2023).
pubmed: 37168857 pmcid: 10164748 doi: 10.3389/fimmu.2023.1176044
Bertelsen, A., Elborn, S. J. & Schock, B. C. Toll like receptor signalling by Prevotella histicola activates alternative NF-κB signalling in Cystic Fibrosis bronchial epithelial cells compared to P. aeruginosa. PLoS ONE 15, e0235803 (2020).
pubmed: 33031374 pmcid: 7544055 doi: 10.1371/journal.pone.0235803
Adamu, B. O. & Lawley, T. D. Bacteriotherapy for the treatment of intestinal dysbiosis caused by Clostridium difficile infection. Curr. Opin. Microbiol. 16, 596–601 (2013).
pubmed: 23866975 pmcid: 3840269 doi: 10.1016/j.mib.2013.06.009
Neves, A. L. et al. The microbiome and its pharmacological targets: therapeutic avenues in cardiometabolic diseases. Curr. Opin. Pharm. 25, 36–44 (2015).
doi: 10.1016/j.coph.2015.09.013
Deckers, J., Marsland, B. J. & von Mutius, E. Protection against allergies: Microbes, immunity, and the farming effect. Eur. J. Immunol. 51, 2387–2398 (2021).
pubmed: 34415577 doi: 10.1002/eji.202048938
Sozanska, B., Blaszczyk, M., Pearce, N. & Cullinan, P. Atopy and allergic respiratory disease in rural Poland before and after accession to the European Union. J. Allergy Clin. Immunol. 133, 1347–1353 (2014).
pubmed: 24342546 doi: 10.1016/j.jaci.2013.10.035
Guest, J. F. & Morris, A. Community-acquired pneumonia: the annual cost to the National Health Service in the UK. Eur. Respir. J. 10, 1530–1534 (1997).
pubmed: 9230242 doi: 10.1183/09031936.97.10071530
Murphy, T. F. Vaccines for nontypeable Haemophilus influenzae: the future is now. Clin. Vaccin. Immunol. 22, 459–466 (2015).
doi: 10.1128/CVI.00089-15
Hanage, W. P. et al. Using multilocus sequence data to define the pneumococcus. J. Bacteriol. 187, 6223–6230 (2005).
pubmed: 16109964 pmcid: 1196147 doi: 10.1128/JB.187.17.6223-6230.2005
Zhang, Q. et al. Airway microbiota in severe asthma and relationship to asthma severity and phenotypes. PLoS ONE 11, e0152724 (2016).
pubmed: 27078029 pmcid: 4831690 doi: 10.1371/journal.pone.0152724
Feigelman, R. et al. Sputum DNA sequencing in cystic fibrosis: non-invasive access to the lung microbiome and to pathogen details. Microbiome 5, 20 (2017).
pubmed: 28187782 pmcid: 5303297 doi: 10.1186/s40168-017-0234-1
Diao, Z., Han, D., Zhang, R. & Li, J. Metagenomics next-generation sequencing tests take the stage in the diagnosis of lower respiratory tract infections. J. Adv. Res. 38, 201–212 (2022).
pubmed: 35572406 doi: 10.1016/j.jare.2021.09.012
Kicic, A., Sutanto, E. N., Stevens, P. T., Knight, D. A. & Stick, S. M. Intrinsic biochemical and functional differences in bronchial epithelial cells of children with asthma. Am. J. Respir. Crit. Care Med. 174, 1110–1118 (2006).
pubmed: 16908868 doi: 10.1164/rccm.200603-392OC
Jackson, D. J. & Johnston, S. L. The role of viruses in acute exacerbations of asthma. J. Allergy Clin. Immunol. 125, 1178–1187 (2010).
pubmed: 20513517 pmcid: 7172767 doi: 10.1016/j.jaci.2010.04.021
Johnston, S. et al. Community study of role of viral infections in exacerbations of asthma in 9-11 year old children. BMJ 310, 1225–1229 (1995).
pubmed: 7767192 pmcid: 2549614 doi: 10.1136/bmj.310.6989.1225
Varkey, J. B. & Varkey, B. Viral infections in patients with chronic obstructive pulmonary disease. Curr. Opin. Pulm. Med. 14, 89–94 (2008).
pubmed: 18303415 doi: 10.1097/MCP.0b013e3282f4a99f
Wedzicha, J. A. Role of viruses in exacerbations of chronic obstructive pulmonary disease. Proc. Am. Thorac. Soc. 1, 115–120 (2004).
pubmed: 16113423 doi: 10.1513/pats.2306030
Arese Lucini, F., Morone, F., Tomassone, M. S. & Makse, H. A. Diversity increases the stability of ecosystems. PLoS ONE 15, e0228692 (2020).
pubmed: 32330134 pmcid: 7182201 doi: 10.1371/journal.pone.0228692
Petit, R. A., 3rd & Read, T. D., Bactopia: a flexible pipeline for complete analysis of bacterial genomes. mSystems 5, e00190–20 (2020).
Jain, C., Rodriguez, R. L., Phillippy, A. M., Konstantinidis, K. T. & Aluru, S. High throughput ANI analysis of 90K prokaryotic genomes reveals clear species boundaries. Nat. Commun. 9, 5114 (2018).
pubmed: 30504855 pmcid: 6269478 doi: 10.1038/s41467-018-07641-9
Cantalapiedra, C. P., Hernández-Plaza, A., Letunic, I., Bork, P. & Huerta-Cepas, J. eggNOG-mapper v2: functional annotation, orthology assignments, and domain prediction at the metagenomic scale. Mol. Biol. Evol. 38, 5825–5829 (2021).
pubmed: 34597405 pmcid: 8662613 doi: 10.1093/molbev/msab293
Paradis, E. & Schliep, K. ape 5.0: an environment for modern phylogenetics and evolutionary analyses in R. Bioinformatics 35, 526–528 (2019).
pubmed: 30016406 doi: 10.1093/bioinformatics/bty633
Letunic, I. & Bork, P. Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res. 49, W293–w296 (2021).
pubmed: 33885785 pmcid: 8265157 doi: 10.1093/nar/gkab301
Cuthbertson, L. et al. The impact of persistent bacterial bronchitis on the pulmonary microbiome of children. PLoS ONE 12, e0190075 (2017).
pubmed: 29281698 pmcid: 5744971 doi: 10.1371/journal.pone.0190075
Salter, S. J. et al. Reagent and laboratory contamination can critically impact sequence-based microbiome analyses. BMC Biol. 12, 87 (2014).
pubmed: 25387460 pmcid: 4228153 doi: 10.1186/s12915-014-0087-z
Rodriguez-Martinez, A. et al. MetaboSignal: a network-based approach for topological analysis of metabotype regulation via metabolic and signaling pathways. Bioinformatics 33, 773–775 (2016).
pmcid: 5408820 doi: 10.1093/bioinformatics/btw697
Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47–e47 (2015).
pubmed: 25605792 pmcid: 4402510 doi: 10.1093/nar/gkv007
Sabatti, C., Service, S. & Freimer, N. False discovery rate in linkage and association genome screens for complex disorders. Genetics 164, 829–833 (2003).
pubmed: 12807801 pmcid: 1462572 doi: 10.1093/genetics/164.2.829
Kumar, L. & M, E. F. Mfuzz: a software package for soft clustering of microarray data. Bioinformation 2, 5–7 (2007).
pubmed: 18084642 pmcid: 2139991 doi: 10.6026/97320630002005
Duttke, S. H., Chang, M. W., Heinz, S. & Benner, C. Identification and dynamic quantification of regulatory elements using total RNA. Genome Res. 29, 1836–1846 (2019).
pubmed: 31649059 pmcid: 6836739 doi: 10.1101/gr.253492.119
Langfelder, P. & Horvath, S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinforma. 9, 559 (2008).
doi: 10.1186/1471-2105-9-559
Ish-Horowicz, J., Olanipekun M., Loeber U., Bartolomaeus T. U. P., Cuthbertson L., Birkner T. CelticFire: Systemic culture and sequence of airway commensal bacteria, related to airway mucosal genomics. Zenodo https://zenodo.org/records/10466935 .
Huerta-Cepas, J., Serra, F. & Bork, P. ETE 3: reconstruction, analysis, and visualization of phylogenomic data. Mol. Biol. Evol. 33, 1635–1638 (2016).
pubmed: 26921390 pmcid: 4868116 doi: 10.1093/molbev/msw046
Ondov, B. D., Bergman, N. H. & Phillippy, A. M. Interactive metagenomic visualization in a Web browser. BMC Bioinforma. 12, 385 (2011).
doi: 10.1186/1471-2105-12-385

Auteurs

Leah Cuthbertson (L)

National Heart and Lung Institute, Imperial College London, London, UK.

Ulrike Löber (U)

Max Delbrück Center for Molecular Medicine (MDC), 13125, Berlin, Germany.
Experimental and Clinical Research Center, A Cooperation of Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Lindenberger Weg 80, 13125, Berlin, Germany.
DZHK (German Centre for Cardiovascular Research), Partner Site, 10785, Berlin, Germany.
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117, Berlin, Germany.

Jonathan S Ish-Horowicz (JS)

National Heart and Lung Institute, Imperial College London, London, UK.
Department of Mathematics, Imperial College London, London, UK.

Claire N McBrien (CN)

National Heart and Lung Institute, Imperial College London, London, UK.

Colin Churchward (C)

National Heart and Lung Institute, Imperial College London, London, UK.

Jeremy C Parker (JC)

National Heart and Lung Institute, Imperial College London, London, UK.

Michael T Olanipekun (MT)

National Heart and Lung Institute, Imperial College London, London, UK.

Conor Burke (C)

Department of Respiratory Medicine, Connolly Hospital, Dublin, Ireland.

Aisling McGowan (A)

Department of Respiratory Medicine, Connolly Hospital, Dublin, Ireland.

Gwyneth A Davies (GA)

Population Data Science and Health Data Research UK BREATHE Hub, Swansea University Medical School, Swansea University, Swansea, UK.
College of Medicine, Institute of Life Science, Swansea University, Swansea, UK.

Keir E Lewis (KE)

College of Medicine, Institute of Life Science, Swansea University, Swansea, UK.
Respiratory Medicine, Hywel Dda University Health Board, Llanelli, UK.

Julian M Hopkin (JM)

College of Medicine, Institute of Life Science, Swansea University, Swansea, UK.

Kian Fan Chung (KF)

National Heart and Lung Institute, Imperial College London, London, UK.

Orla O'Carroll (O)

Department of Respiratory Medicine, Connolly Hospital, Dublin, Ireland.

John Faul (J)

Department of Respiratory Medicine, Connolly Hospital, Dublin, Ireland.

Joy Creaser-Thomas (J)

College of Medicine, Institute of Life Science, Swansea University, Swansea, UK.

Mark Andrews (M)

Respiratory Medicine, Hywel Dda University Health Board, Llanelli, UK.

Robin Ghosal (R)

Respiratory Medicine, Hywel Dda University Health Board, Llanelli, UK.

Stefan Piatek (S)

National Heart and Lung Institute, Imperial College London, London, UK.

Saffron A G Willis-Owen (SAG)

National Heart and Lung Institute, Imperial College London, London, UK.

Theda U P Bartolomaeus (TUP)

Max Delbrück Center for Molecular Medicine (MDC), 13125, Berlin, Germany.
Experimental and Clinical Research Center, A Cooperation of Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Lindenberger Weg 80, 13125, Berlin, Germany.
DZHK (German Centre for Cardiovascular Research), Partner Site, 10785, Berlin, Germany.
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117, Berlin, Germany.

Till Birkner (T)

Max Delbrück Center for Molecular Medicine (MDC), 13125, Berlin, Germany.
Experimental and Clinical Research Center, A Cooperation of Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Lindenberger Weg 80, 13125, Berlin, Germany.
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117, Berlin, Germany.

Sarah Dwyer (S)

National Heart and Lung Institute, Imperial College London, London, UK.

Nitin Kumar (N)

Host-Microbiota Interactions Laboratory, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.

Elena M Turek (EM)

National Heart and Lung Institute, Imperial College London, London, UK.

A William Musk (A)

School of Population and Global Health, The University of Western Australia, Perth, WA, Australia.
Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Perth, WA, Australia.
Department of Respiratory Medicine Sir Charles Gairdner Hospital, Perth, WA, Australia.

Jennie Hui (J)

School of Population and Global Health, The University of Western Australia, Perth, WA, Australia.
Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Perth, WA, Australia.

Michael Hunter (M)

School of Population and Global Health, The University of Western Australia, Perth, WA, Australia.
Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Perth, WA, Australia.

Alan James (A)

School of Population and Global Health, The University of Western Australia, Perth, WA, Australia.
Department of Respiratory Medicine Sir Charles Gairdner Hospital, Perth, WA, Australia.
Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia.

Marc-Emmanuel Dumas (ME)

National Heart and Lung Institute, Imperial College London, London, UK.
Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
U1283 INSERM / UMR8199 CNRS, Institut Pasteur de Lille, Lille University Hospital, European Genomic Institute for Diabetes, University of Lille, Lille, France.
McGill Genome Centre, McGill University, Montréal, QC, Canada.

Sarah Filippi (S)

Department of Mathematics, Imperial College London, London, UK.

Michael J Cox (MJ)

University of Birmingham College of Medical and Dental Sciences, 150183, Institute of Microbiology and Infection, Birmingham, UK.

Trevor D Lawley (TD)

Host-Microbiota Interactions Laboratory, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.

Sofia K Forslund (SK)

Max Delbrück Center for Molecular Medicine (MDC), 13125, Berlin, Germany. sofia.forslund@mdc-berlin.de.
Experimental and Clinical Research Center, A Cooperation of Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Lindenberger Weg 80, 13125, Berlin, Germany. sofia.forslund@mdc-berlin.de.
DZHK (German Centre for Cardiovascular Research), Partner Site, 10785, Berlin, Germany. sofia.forslund@mdc-berlin.de.
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117, Berlin, Germany. sofia.forslund@mdc-berlin.de.
Structural and Computational Biology Unit, European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117, Heidelberg, Germany. sofia.forslund@mdc-berlin.de.

Miriam F Moffatt (MF)

National Heart and Lung Institute, Imperial College London, London, UK. m.moffatt@imperial.ac.uk.

William O C Cookson (WOC)

National Heart and Lung Institute, Imperial College London, London, UK. w.cookson@imperial.ac.uk.

Classifications MeSH