Characterization of a sponge microbiome using an integrative genome-centric approach

Abstract

Marine sponges often host diverse and species-specific communities of microorganisms that are critical for host health. Previous functional genomic investigations of the sponge microbiome have focused primarily on specific symbiont lineages, which frequently make up only a small fraction of the overall community. Here, we undertook genome-centric analysis of the symbiont community in the model species Ircinia ramosa and analyzed 259 unique, high-quality metagenome-assembled genomes (MAGs) that comprised 74% of the I. ramosa microbiome. Addition of these MAGs to genome trees containing all publicly available microbial sponge symbionts increased phylogenetic diversity by 32% within the archaea and 41% within the bacteria. Metabolic reconstruction of the MAGs showed extensive redundancy across taxa for pathways involved in carbon fixation, B-vitamin synthesis, taurine metabolism, sulfite oxidation, and most steps of nitrogen metabolism. Through the acquisition of all major taxa present within the I. ramosa microbiome, we were able to analyze the functional potential of a sponge-associated microbial community in unprecedented detail. Critical functions, such as carbon fixation, which had previously only been assigned to a restricted set of sponge-associated organisms, were actually spread across diverse symbiont taxa, whereas other essential pathways, such as ammonia oxidation, were confined to specific keystone taxa.

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Fig. 1: Combined archaeal and bacterial phylogenetic tree based on single copy marker proteins (inferred with GTDB).
Fig. 2: Metabolic reconstruction and proposed exchange of carbon, nitrogen, sulfur, and vitamins between Ircinia ramosa symbionts and the host.

Data availability

All data for this study can be found under the Bioproject ID PRJNA555144. The metagenomic reads for I. ramosa are available at NCBI under the accession numbers SRR9841427-SRR9841447 and the MAGs can be found under the accession numbers VXLI00000000-VYGU00000000, which are also shown in Table S1.

Change history

  • 05 February 2020

    The supplementary information files were initially linked incorrectly but have since been corrected. All files were available at publication.

References

  1. 1.

    Bell JJ. The functional roles of marine sponges. Estuar Coast Shelf Sci. 2008;79:341–53.

  2. 2.

    De Goeij JM, Van Oevelen D, Vermeij MJ, Osinga R, Middelburg JJ, de Goeij AF, et al. Surviving in a marine desert: the sponge loop retains resources within coral reefs. Science. 2013;342:108–10.

  3. 3.

    Beazley LI, Kenchington EL, Murillo FJ, Sacau MdM. Deep-sea sponge grounds enhance diversity and abundance of epibenthic megafauna in the Northwest Atlantic. ICES J Mar Sci. 2013;70:1471–90.

  4. 4.

    Webster NS, Thomas T. The sponge hologenome. MBio. 2016;7:e00135–16.

  5. 5.

    Pita L, Rix L, Slaby BM, Franke A, Hentschel U. The sponge holobiont in a changing ocean: from microbes to ecosystems. Microbiome. 2018;6:46.

  6. 6.

    Hentschel U, Fieseler L, Wehrl M, Gernert C, Steinert M, Hacker J, et al. Microbial diversity of marine sponges. In: Mueller W, editor, Marine molecular biotechnology. Berlin; Springer: 2003. p. 59–88.

  7. 7.

    Thomas T, Moitinho-Silva L, Lurgi M, Björk JR, Easson C, Astudillo-García C, et al. Diversity, structure and convergent evolution of the global sponge microbiome. Nat Commun. 2016;7:11870.

  8. 8.

    Taylor MW, Tsai P, Simister RL, Deines P, Botte E, Ericson G, et al. ‘Sponge-specific’ bacteria are widespread (but rare) in diverse marine environments. ISME J. 2013;7:438.

  9. 9.

    Fan L, Reynolds D, Liu M, Stark M, Kjelleberg S, Webster NS, et al. Functional equivalence and evolutionary convergence in complex communities of microbial sponge symbionts. Proc Natl Acad Sci USA. 2012;109:E1878–87.

  10. 10.

    Karimi E, Keller-Costa T, Slaby BM, Cox CJ, da Rocha UN, Hentschel U, et al. Genomic blueprints of sponge-prokaryote symbiosis are shared by low abundant and cultivatable Alphaproteobacteria. Sci Rep. 2019;9:1999.

  11. 11.

    Podell S, Blanton JM, Neu A, Agarwal V, Biggs JS, Moore BS, et al. Pangenomic comparison of globally distributed Poribacteria associated with sponge hosts and marine particles. ISME J. 2019;13:468–81.

  12. 12.

    Slaby BM, Hackl T, Horn H, Bayer K, Hentschel U. Metagenomic binning of a marine sponge microbiome reveals unity in defense but metabolic specialization. ISME J. 2017;11:2465–78.

  13. 13.

    Diez-Vives C, Esteves AIS, Costa R, Nielsen S, Thomas T. Detecting signatures of a sponge-associated lifestyle in bacterial genomes. EMR. 2018;10:433–43.

  14. 14.

    Thomas T, Rusch D, DeMaere MZ, Yung PY, Lewis M, Halpern A, et al. Functional genomic signatures of sponge bacteria reveal unique and shared features of symbiosis. ISME J. 2010;4:1557–67.

  15. 15.

    Sturm M, Schroeder C, Bauer P. SeqPurge: highly-sensitive adapter trimming for paired-end NGS data. BMC Bioinforma. 2016;17:208.

  16. 16.

    Nurk S, Meleshko D, Korobeynikov A, Pevzner PA. metaSPAdes: a new versatile metagenomic assembler. Genome Res. 2017;27:824–34.

  17. 17.

    Li H, Durbin R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics. 2009;25:1754–60.

  18. 18.

    Graham ED, Heidelberg JF, Tully BJ. BinSanity: unsupervised clustering of environmental microbial assemblies using coverage and affinity propagation. PeerJ. 2017;5:e3035.

  19. 19.

    Imelfort M, Parks D, Woodcroft BJ, Dennis P, Hugenholtz P, Tyson GW. GroopM: an automated tool for the recovery of population genomes from related metagenomes. PeerJ. 2014;2:e603.

  20. 20.

    Kang DD, Froula J, Egan R, Wang Z. MetaBAT, an efficient tool for accurately reconstructing single genomes from complex microbial communities. PeerJ. 2015;3:e1165.

  21. 21.

    Parks DH, Imelfort M, Skennerton CT, Hugenholtz P, Tyson GW. CheckM: assessing the quality of microbial genomes recovered from isolates, single cells, and metagenomes. Genome Res. 2015;25:1043–55.

  22. 22.

    Wu Y-W, Simmons BA, Singer SW. MaxBin 2.0: an automated binning algorithm to recover genomes from multiple metagenomic datasets. Bioinformatics. 2015;32:605–7.

  23. 23.

    Jain C, Rodriguez-R LM, Phillippy AM, Konstantinidis KT, Aluru S. High throughput ANI analysis of 90K prokaryotic genomes reveals clear species boundaries. Nat Commun. 2018;9:5114.

  24. 24.

    Matsen FA, Kodner RB, Armbrust EV. pplacer: linear time maximum-likelihood and Bayesian phylogenetic placement of sequences onto a fixed reference tree. BMC Bioinforma. 2010;11:538.

  25. 25.

    Parks DH, Chuvochina M, Waite DW, Rinke C, Skarshewski A, Chaumeil P-A, et al. A standardized bacterial taxonomy based on genome phylogeny substantially revises the tree of life. Nat Biotechnol. 2018;36:996–1004.

  26. 26.

    Olm MR, Brown CT, Brooks B, Banfield JF. dRep: a tool for fast and accurate genomic comparisons that enables improved genome recovery from metagenomes through de-replication. ISME J. 2017;11:2864–8.

  27. 27.

    R Core Team R: a language and environment for statistical computing (R Foundation for Statistical Computing, 2013). http://www.R-project.org/.

  28. 28.

    Boyd JA, Woodcroft BJ, Tyson GW. GraftM: a tool for scalable, phylogenetically informed classification of genes within metagenomes. Nucleic Acids Res. 2018;46:e59-e.

  29. 29.

    Quast C, Pruesse E, Yilmaz P, Gerken J, Schweer T, Yarza P, et al. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res. 2013;41:D590–6.

  30. 30.

    Li W, Godzik A. Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences. Bioinformatics. 2006;22:1658–9.

  31. 31.

    Fu L, Niu B, Zhu Z, Wu S, Li W. CD-HIT: accelerated for clustering the next-generation sequencing data. Bioinformatics. 2012;28:3150–2.

  32. 32.

    Parks DH, Rinke C, Chuvochina M, Chaumeil P-A, Woodcroft BJ, Evans PN, et al. Recovery of nearly 8000 metagenome-assembled genomes substantially expands the tree of life. Nat Microbiol. 2017;2:1533–42.

  33. 33.

    Letunic I, Bork P. Interactive tree of life (iTOL) v3: an online tool for the display and annotation of phylogenetic and other trees. Nucleic Acids Res. 2016;44:W242–5.

  34. 34.

    Finn RD, Coggill P, Eberhardt RY, Eddy SR, Mistry J, Mitchell AL, et al. The Pfam protein families database: towards a more sustainable future. Nucleic Acids Res. 2015;44:D279–85.

  35. 35.

    Kanehisa M, Sato Y, Kawashima M, Furumichi M, Tanabe M. KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res. 2015;44:D457–62.

  36. 36.

    Erwin PM, Lopez-Legentil S, Gonzalez-Pech R, Turon X. A specific mix of generalists: bacterial symbionts in Mediterranean Ircinia spp. FEMS Microbiol Ecol. 2012;79:619–37.

  37. 37.

    Esteves AI, Hardoim CC, Xavier JR, Goncalves JM, Costa R. Molecular richness and biotechnological potential of bacteria cultured from Irciniidae sponges in the north-east Atlantic. FEMS Microbiol Ecol. 2013;85:519–36.

  38. 38.

    Bayer K, Jahn MT, Slaby BM, Moitinho-Silva L, Hentschel U. Marine sponges as chloroflexi hot spots: genomic insights and high-resolution visualization of an abundant and diverse symbiotic clade. MSystems. 2018;3:e00150–18.

  39. 39.

    Van Soest RWM, Boury-Esnault N, Hooper JNA, Rützler K, de Voogd NJ, Alvarez B, et al. World Porifera database. (2018) http://www.marinespecies.org/porifera.

  40. 40.

    Wilkinson CR. Net primary productivity in coral reef sponges. Science. 1983;219:410–2.

  41. 41.

    Vacelet J, Fiala-Médioni A, Fisher C, Boury-Esnault N. Symbiosis between methane-oxidizing bacteria and a deep-sea carnivorous cladorhizid sponge. Mar Ecol Prog Ser. 1996;145:77–85.

  42. 42.

    Gao Z-M, Wang Y, Tian R-M, Wong YH, Batang ZB, Al-Suwailem AM, et al. Symbiotic adaptation drives genome streamlining of the cyanobacterial sponge symbiont “Candidatus Synechococcus spongiarum”. MBio. 2014;5:e00079–14.

  43. 43.

    Liu F, Li J, Feng G, Li Z. New genomic insights into “Entotheonella” symbionts in Theonella swinhoei: Mixotrophy, anaerobic adaptation, resilience, and interaction. Front Microbiol. 2016;7:1333.

  44. 44.

    Moitinho-Silva L, Díez-Vives C, Batani G, Esteves AI, Jahn MT, Thomas T. Integrated metabolism in sponge–microbe symbiosis revealed by genome-centered metatranscriptomics. ISME J. 2017;11:1651–66.

  45. 45.

    Tian RM, Sun J, Cai L, Zhang WP, Zhou GW, Qiu JW, et al. The deep-sea glass sponge Lophophysema eversa harbours potential symbionts responsible for the nutrient conversions of carbon, nitrogen and sulfur. Environ Microbiol. 2016;18:2481–94.

  46. 46.

    Achlatis M, Pernice M, Green K, Guagliardo P, Kilburn MR, Hoegh-Guldberg O, et al. Single-cell measurement of ammonium and bicarbonate uptake within a photosymbiotic bioeroding sponge. ISME J. 2018;12:1308.

  47. 47.

    Moeller FU, Webster NS, Herbold CW, Behnam F, Domman D, Albertsen M, et al. Characterization of a thaumarchaeal symbiont that drives incomplete nitrification in the tropical sponge Ianthella basta. Environ Microbiol. 2019;21:527234.

  48. 48.

    Hügler M, Sievert SM. Beyond the Calvin cycle: autotrophic carbon fixation in the ocean. Annu Rev Mar Sci. 2011;3:261–89.

  49. 49.

    Siegl A, Kamke J, Hochmuth T, Piel J, Richter M, Liang C, et al. Single-cell genomics reveals the lifestyle of Poribacteria, a candidate phylum symbiotically associated with marine sponges. ISME J. 2011;5:61–70.

  50. 50.

    Astudillo‐García C, Slaby BM, Waite DW, Bayer K, Hentschel U, Taylor MW. Phylogeny and genomics of SAUL, an enigmatic bacterial lineage frequently associated with marine sponges. Environ Microbiol. 2018;20:561–76.

  51. 51.

    Kamke J, Sczyrba A, Ivanova N, Schwientek P, Rinke C, Mavromatis K, et al. Single-cell genomics reveals complex carbohydrate degradation patterns in poribacterial symbionts of marine sponges. ISME J. 2013;7:2287–300.

  52. 52.

    Bell JJ, Bennett HM, Rovellini A, Webster NS. Sponges to be winners under near-future climate scenarios. Biosci. 2018;68:955–68.

  53. 53.

    Hentschel U, Piel J, Degnan SM, Taylor MW. Genomic insights into the marine sponge microbiome. Nat Rev Microbiol. 2012;10:641–54.

  54. 54.

    Bayer K, Schmitt S, Hentschel U. Physiology, phylogeny and in situ evidence for bacterial and archaeal nitrifiers in the marine sponge Aplysina aerophoba. Environ Microbiol. 2008;10:2942–55.

  55. 55.

    Taylor MW, Radax R, Steger D, Wagner M. Sponge-associated microorganisms: evolution, ecology, and biotechnological potential. Microbiol Mol Biol Rev. 2007;71:295–347.

  56. 56.

    Ward BB. Nitrification in marine systems. In: Capone DG, Bronk DA, Mulholland MR, Carpenter EJ, editors. Nitrogen in the marine environment. 2nd ed. Amsterdam: Elsevier Press; 2008. p. 199–262.

  57. 57.

    Han M, Li Z, Zhang F. The ammonia oxidizing and denitrifying prokaryotes associated with sponges from different sea areas. Micro Ecol. 2013;66:427–36.

  58. 58.

    Radax R, Hoffmann F, Rapp HT, Leininger S, Schleper C. Ammonia-oxidizing archaea as main drivers of nitrification in cold-water sponges. Environ Microbiol. 2012;14:909–23.

  59. 59.

    Mohammadi SS, Pol A, van Alen T, Jetten MS, Op den Camp HJ. Ammonia oxidation and nitrite reduction in the verrucomicrobial methanotroph Methylacidiphilum fumariolicum SolV. Front Microbiol. 2017;8:1901.

  60. 60.

    De la Torre JR, Walker CB, Ingalls AE, Könneke M, Stahl DA. Cultivation of a thermophilic ammonia oxidizing archaeon synthesizing crenarchaeol. Environ Microbiol. 2008;10:810–8.

  61. 61.

    Könneke M, Bernhard AE, José R, Walker CB, Waterbury JB, Stahl DA. Isolation of an autotrophic ammonia-oxidizing marine archaeon. Nature. 2005;437:543–6.

  62. 62.

    Maldonado M, Ribes M, van Duyl FC. Nutrient fluxes through sponges: biology, budgets, and ecological implications. Adv Mar Biol. 2012;62:113–82.

  63. 63.

    Bondarev V, Richter M, Romano S, Piel J, Schwedt A, Schulz-Vogt HN. The genus pseudovibrio contains metabolically versatile bacteria adapted for symbiosis. Environ Microbiol. 2013;15:2095–113.

  64. 64.

    Karimi E, Slaby BM, Soares AR, Blom J, Hentschel U, Costa R. Metagenomic binning reveals versatile nutrient cycling and distinct adaptive features in alphaproteobacterial symbionts of marine sponges. FEMS Microbiol Ecol. 2018;94:74.

  65. 65.

    Liu M, Fan L, Zhong L, Kjelleberg S, Thomas T. Metaproteogenomic analysis of a community of sponge symbionts. ISME J. 2012;6:1515–25.

  66. 66.

    Fiore CL, Baker DM, Lesser MP. Nitrogen biogeochemistry in the Caribbean sponge, Xestospongia muta: a source or sink of dissolved inorganic nitrogen? PLoS ONE. 2013;8:e72961.

  67. 67.

    Hoffmann F, Radax R, Woebken D, Holtappels M, Lavik G, Rapp HT, et al. Complex nitrogen cycling in the sponge Geodia barretti. Environ Microbiol. 2009;11:2228–43.

  68. 68.

    Schläppy M-L, Schöttner SI, Lavik G, Kuypers MM, de Beer D, Hoffmann F. Evidence of nitrification and denitrification in high and low microbial abundance sponges. Mar Biol. 2010;157:593–602.

  69. 69.

    Emura C, Higuchi R, Miyamoto T. Irciniasulfonic acid B, a novel taurine conjugated fatty acid derivative from a Japanese marine sponge, Ircinia sp. Tetrahedron. 2006;62:5682–5.

  70. 70.

    Gauthier M-EA, Watson JR, Degnan SM. Draft genomes shed light on the dual bacterial symbiosis that dominates the microbiome of the coral reef sponge Amphimedon queenslandica. Front Mar Sci. 2016;3:196.

  71. 71.

    Lackner G, Peters EE, Helfrich EJ, Piel J. Insights into the lifestyle of uncultured bacterial natural product factories associated with marine sponges. Proc Natl Acad Sci USA. 2017;114:E347–56.

  72. 72.

    Tian RM, Wang Y, Bougouffa S, Gao ZM, Cai L, Bajic V, et al. Genomic analysis reveals versatile heterotrophic capacity of a potentially symbiotic sulfur‐oxidizing bacterium in sponge. Environ Microbiol. 2014;16:3548–61.

  73. 73.

    Hoffmann F, Larsen O, Thiel V, Rapp HT, Pape T, Michaelis W, et al. An anaerobic world in sponges. Geomicrobiol J. 2005;22:1–10.

  74. 74.

    Combs GF Jr, McClung JP. The vitamins: fundamental aspects in nutrition and health. 5th ed. San Diego: Academic Press Inc; 2016.

  75. 75.

    Tomiki T, Saitou N. Phylogenetic analysis of proteins associated in the four major energy metabolism systems: photosynthesis, aerobic respiration, denitrification, and sulfur respiration. J Mol Evol. 2004;59:158–76.

  76. 76.

    Croft MT, Lawrence AD, Raux-Deery E, Warren MJ, Smith AG. Algae acquire vitamin B 12 through a symbiotic relationship with bacteria. Nature. 2005;438:90–3.

  77. 77.

    Moriyama M, Nikoh N, Hosokawa T, Fukatsu T. Riboflavin provisioning underlies Wolbachia’s fitness contribution to its insect host. MBio. 2015;6:e01732–15.

  78. 78.

    Fiore CL, Labrie M, Jarett JK, Lesser MP. Transcriptional activity of the giant barrel sponge, Xestospongia muta Holobiont: molecular evidence for metabolic interchange. Front Microbiol. 2015;6:364.

  79. 79.

    Hallam SJ, Konstantinidis KT, Putnam N, Schleper C, Watanabe Y-i, Sugahara J, et al. Genomic analysis of the uncultivated marine crenarchaeote Cenarchaeum symbiosum. Proc Natl Acad Sci USA. 2006;103:18296–301.

  80. 80.

    Kamke J, Rinke C, Schwientek P, Mavromatis K, Ivanova N, Sczyrba A, et al. The candidate phylum Poribacteria by single-cell genomics: new insights into phylogeny, cell-compartmentation, eukaryote-like repeat proteins, and other genomic features. PLoS ONE. 2014;9:e87353.

  81. 81.

    Liu MY, Kjelleberg S, Thomas T. Functional genomic analysis of an uncultured δ-proteobacterium in the sponge Cymbastela concentrica. ISME J. 2011;5:427–35.

  82. 82.

    Díez-Vives C, Moitinho-Silva L, Nielsen S, Reynolds D, Thomas T. Expression of eukaryotic‐like protein in the microbiome of sponges. Mol Ecol. 2017;26:1432–51.

  83. 83.

    Moitinho-Silva L, Seridi L, Ryu T, Voolstra CR, Ravasi T, Hentschel U. Revealing microbial functional activities in the Red Sea sponge Stylissa carteri by metatranscriptomics. Environ Microbiol. 2014;16:3683–98.

  84. 84.

    Costa TR, Felisberto-Rodrigues C, Meir A, Prevost MS, Redzej A, Trokter M, et al. Secretion systems in Gram-negative bacteria: structural and mechanistic insights. Nat Rev Microbiol. 2015;13:343–59.

  85. 85.

    Nguyen MT, Liu M, Thomas T. Ankyrin-repeat proteins from sponge symbionts modulate amoebal phagocytosis. Mol Ecol. 2014;23:1635–45.

  86. 86.

    Smith TF, Gaitatzes C, Saxena K, Neer EJ. The WD repeat: a common architecture for diverse functions. Trends Biochem Sci. 1999;24:181–5.

  87. 87.

    Pan X, Lührmann A, Satoh A, Laskowski-Arce MA, Roy CR. Ankyrin repeat proteins comprise a diverse family of bacterial type IV effectors. Science. 2008;320:1651–4.

  88. 88.

    Jernigan KK, Bordenstein SR. Ankyrin domains across the tree of life. PeerJ. 2014;2:e264.

  89. 89.

    Al-Khodor S, Price CT, Kalia A, Kwaik YA. Functional diversity of ankyrin repeats in microbial proteins. Trends Microbiol. 2010;18:132–9.

  90. 90.

    Speare L, Cecere AG, Guckes KR, Smith S, Wollenberg MS, Mandel MJ, et al. Bacterial symbionts use a type VI secretion system to eliminate competitors in their natural host. Proc Natl Acad Sci USA. 2018;115:E8528–37.

  91. 91.

    Karimi E, Ramos M, Gonçalves J, Xavier JR, Reis MP, Costa R. Comparative metagenomics reveals the distinctive adaptive features of the Spongia officinalis endosymbiotic consortium. Front Microbiol. 2017;8:2499.

  92. 92.

    Yano K, Shibata S, Chen WL, Sato S, Kaneko T, Jurkiewicz A, et al. CERBERUS, a novel U-box protein containing WD-40 repeats, is required for formation of the infection thread and nodule development in the legume–Rhizobium symbiosis. Plant J. 2009;60:168–80.

  93. 93.

    Schläppy M-L, Hoffmann F, Røy H, Wijffels RH, Mendola D, Sidri M, et al. Oxygen dynamics and flow patterns of Dysidea avara (Porifera: Demospongiae). J Mar Biol Assoc UK. 2007;87:1677–82.

  94. 94.

    McCann KS. The diversity–stability debate. Nature. 2000;405:228–33.

  95. 95.

    Bennett HM, Altenrath C, Woods L, Davy SK, Webster NS, Bell JJ. Interactive effects of temperature and pCO 2 on sponges: from the cradle to the grave. Glob Chang Biol. 2017;23:2031–46.

  96. 96.

    Cowart J, Henkel T, McMurray S, Pawlik JR. Sponge orange band (SOB): a pathogenic-like condition of the giant barrel sponge, Xestospongia muta. Coral Reefs. 2006;25:513.

  97. 97.

    Wilson MC, Mori T, Rückert C, Uria AR, Helf MJ, Takada K, et al. An environmental bacterial taxon with a large and distinct metabolic repertoire. Nature. 2014;506:58–62.

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Acknowledgements

We acknowledge Andrea Severati and other staff at the Australian Institute of Marine Science SeaSim facility who assisted with sample collection and sponge husbandry.

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Correspondence to Nicole S. Webster.

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Engelberts, J.P., Robbins, S.J., de Goeij, J.M. et al. Characterization of a sponge microbiome using an integrative genome-centric approach. ISME J (2020). https://doi.org/10.1038/s41396-020-0591-9

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