Multi-way modelling of oral microbial dynamics and host-microbiome interactions during induced gingivitis.


Journal

NPJ biofilms and microbiomes
ISSN: 2055-5008
Titre abrégé: NPJ Biofilms Microbiomes
Pays: United States
ID NLM: 101666944

Informations de publication

Date de publication:
19 Sep 2024
Historique:
received: 07 04 2024
accepted: 12 09 2024
medline: 20 9 2024
pubmed: 20 9 2024
entrez: 19 9 2024
Statut: epublish

Résumé

Gingivitis-the inflammation of the gums-is a reversible stage of periodontal disease. It is caused by dental plaque formation due to poor oral hygiene. However, gingivitis susceptibility involves a complex set of interactions between the oral microbiome, oral metabolome and the host. In this study, we investigated the dynamics of the oral microbiome and its interactions with the salivary metabolome during experimental gingivitis in a cohort of 41 systemically healthy participants. We use Parallel Factor Analysis (PARAFAC), which is a multi-way generalization of Principal Component Analysis (PCA) that can model the variability in the response due to subjects, variables and time. Using the modelled responses, we identified microbial subcommunities with similar dynamics that connect to the magnitude of the gingivitis response. By performing high level integration of the predicted metabolic functions of the microbiome and salivary metabolome, we identified pathways of interest that describe the changing proportions of Gram-positive and Gram-negative microbiota, variation in anaerobic bacteria, biofilm formation and virulence.

Identifiants

pubmed: 39300083
doi: 10.1038/s41522-024-00565-x
pii: 10.1038/s41522-024-00565-x
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

89

Informations de copyright

© 2024. The Author(s).

Références

Petersen, P. E., Bourgeois, D., Ogawa, H., Estupinan-Day, S. & Ndiaye, C. The global burden of oral diseases and risks to oral health. Bull. World Health Organ. (2005).
Peres, M. A. et al. Oral diseases: a global public health challenge. Lancet 394, 249–260 (2019).
pubmed: 31327369 doi: 10.1016/S0140-6736(19)31146-8
WHO. Global Oral Health Status Report: Towards Universal Health Coverage for Oral Health by 2030. https://www.who.int/publications/i/item/9789240061484 (2022).
Widström, E., Eaton, K. & Vanobbergen, J. Oral healthcare systems in the Extended European Union, partim:[Oral Health care system in] Belgium. Oral. Health Prev. Dent. 2, 155–157 (2004).
pubmed: 15641621
Huang, S. et al. Predictive modeling of gingivitis severity and susceptibility via oral microbiota. ISME J. 8, 1768–1780 (2014).
pubmed: 24646694 pmcid: 4139724 doi: 10.1038/ismej.2014.32
Chapple, I. L. C. et al. Primary prevention of periodontitis: managing gingivitis. J. Clin. Periodontol. 42, S71–S76 (2015).
pubmed: 25639826 doi: 10.1111/jcpe.12366
Curtis, M. A., Diaz, P. I. & Van Dyke, T. E. The role of the microbiota in periodontal disease. Periodontol 2000 83, 14–25 (2020).
pubmed: 32385883 doi: 10.1111/prd.12296
Löe, H., Theilade, E. & Jensen, S. B. Experimental Gingivitis in Man. J. Periodontol. 36, 177–187 (1965).
doi: 10.1902/jop.1965.36.3.177
Murakami, S., Mealey, B. L., Mariotti, A. & Chapple, I. L. C. Dental plaque–induced gingival conditions. J. Clin. Periodontol. 45, S17–S27 (2018).
pubmed: 29926503 doi: 10.1111/jcpe.12937
Han, L. et al. Hygiene practices among young adolescents aged 12-15 years in low- and middle-income countries: a population-based study. J. Glob. Health 10, 020436 (2020).
pubmed: 33312503 pmcid: 7719273 doi: 10.7189/jogh.10.020436
Chapple, I. L. C. et al. Periodontal health and gingival diseases and conditions on an intact and a reduced periodontium: Consensus report of workgroup 1 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J. Periodontol. 89, S74–S84 (2018).
pubmed: 29926944
Kilian, M. et al. The oral microbiome – an update for oral healthcare professionals. Br. Dent. J. 221, 657–666 (2016).
pubmed: 27857087 doi: 10.1038/sj.bdj.2016.865
Van Der Velden, U., Kuzmanova, D. & Chapple, I. L. C. Micronutritional approaches to periodontal therapy. J. Clin. Periodontol. 38, 142–158 (2011).
pubmed: 21323711 doi: 10.1111/j.1600-051X.2010.01663.x
Bergström, J. & Preber, H. The influence of cigarette smoking on the development of experimental gingivitis. J. Periodontal Res. 21, 668–676 (1986).
pubmed: 2948000 doi: 10.1111/j.1600-0765.1986.tb01504.x
Nibali, L., Di Iorio, A., Tu, Y. & Vieira, A. R. Host genetics role in the pathogenesis of periodontal disease and caries. J. Clin. Periodontol. 44, (2017).
Axelsson, P., Lindhe, J. & Nyström, B. On the prevention of caries and periodontal disease. J. Clin. Periodontol. 18, 182–189 (1991).
pubmed: 2061418 doi: 10.1111/j.1600-051X.1991.tb01131.x
Guk, H.-J., Lee, E.-S., Jung, U.-W. & Kim, B.-I. Red fluorescence of Interdental plaque for screening of gingival health. Photodiagnosis Photodyn. Ther. 29, 101636 (2020).
pubmed: 31917322 doi: 10.1016/j.pdpdt.2019.101636
van der Veen, M. H., Volgenant, C. M. C., Keijser, B., ten Cate, J., Bob, M. & Crielaard, W. Dynamics of red fluorescent dental plaque during experimental gingivitis—A cohort study. J. Dent. 48, 71–76 (2016).
pubmed: 26921667 doi: 10.1016/j.jdent.2016.02.010
Abusleme, L., Hoare, A., Hong, B. & Diaz, P. I. Microbial signatures of health, gingivitis, and periodontitis. Periodontol 2000 86, 57–78 (2021).
pubmed: 33690899 doi: 10.1111/prd.12362
Diaz, P. I., Hoare, A. & Hong, B.-Y. Subgingival Microbiome Shifts and Community Dynamics in Periodontal Diseases. J. Calif. Dent. Assoc. 44, 421–435 (2016).
pubmed: 27514154
Kistler, J. O., Booth, V., Bradshaw, D. J. & Wade, W. G. Bacterial Community Development in Experimental Gingivitis. PLoS ONE 8, e71227 (2013).
pubmed: 23967169 pmcid: 3743832 doi: 10.1371/journal.pone.0071227
Schincaglia, G. P. et al. Clinical, Immune, and Microbiome Traits of Gingivitis and Peri-implant Mucositis. J. Dent. Res. 96, 47–55 (2017).
pubmed: 28033066 doi: 10.1177/0022034516668847
Diaz, P. I., Zilm, P. S. & Rogers, A. H. Fusobacterium nucleatum supports the growth of Porphyromonas gingivalis in oxygenated and carbon-dioxide-depleted environments. Microbiology 148, 467–472 (2002).
pubmed: 11832510 doi: 10.1099/00221287-148-2-467
Ter Steeg, P. F., Van Der Hoeven, J. S., De Jong, M. H., Van Munster, P. J. J. & Jansen, M. J. H. Modelling the Gingival Pocket by Enrichment of Subgingival Microflora in Human Serum in Chemostats. Microb. Ecol. Health Dis. 1, 73–84 (1988).
Dawes, C. & Wong, D. T. W. Role of Saliva and Salivary Diagnostics in the Advancement of Oral Health. J. Dent. Res. 98, 133–141 (2019).
pubmed: 30782091 pmcid: 6900436 doi: 10.1177/0022034518816961
Proctor, G. B. The physiology of salivary secretion. Periodontol 2000 70, 11–25 (2016).
pubmed: 26662479 doi: 10.1111/prd.12116
König, K. G. & Navia, J. M. Nutritional role of sugars in oral health. Am. J. Clin. Nutr. 62, 275S–282S (1995).
pubmed: 7598084 doi: 10.1093/ajcn/62.1.275S
Marsh, P. D. Sugar, fluoride, pH and microbial homeostasis in dental plaque. Proc. Finn. Dent. Soc. Suom. Hammaslaakariseuran Toim. 87, 515–525 (1991).
Prodan, A. et al. Effect of experimental gingivitis induction and erythritol on the salivary metabolome and functional biochemistry of systemically healthy young adults. Metabolomics 12, 147 (2016).
doi: 10.1007/s11306-016-1096-4
Carroll, J. D. & Chang, J.-J. Analysis of individual differences in multidimensional scaling via an n-way generalization of “Eckart-Young” decomposition. Psychometrika 35, 283–319 (1970).
doi: 10.1007/BF02310791
Harshman, R. A. Foundations of the PARAFAC procedure: Models and conditions for an “explanatory” multimodal factor analysis. UCLA Working Papers in Phonetics 16, 1–84 (1970).
Bro, R. PARAFAC. Tutorial and applications. Chemom. Intell. Lab. Syst. 38, 49–171 (1997).
doi: 10.1016/S0169-7439(97)00032-4
Bro, R. & Kiers, H. A new Efficient Method for Determining the Number of Components in PARAFAC Models. J. Chemom. 17, 274–286 (2003).
doi: 10.1002/cem.801
Lorenzo-Seva, U. & ten Berge, J. M. F. Tucker’s congruence coefficient as a meaningful index of factor similarity. Methodol. Eur. J. Res. Methods Behav. Soc. Sci. 2, 57–64 (2006).
Tucker, L. R. A Method for Synthesis of Factor Analysis Studies. 984 (Educational Testing Service Princeton, NJ, 1951).
Kirst, M. E. et al. Dysbiosis and Alterations in Predicted Functions of the Subgingival Microbiome in Chronic Periodontitis. Appl. Environ. Microbiol. 81, 783–793 (2015).
pubmed: 25398868 pmcid: 4277562 doi: 10.1128/AEM.02712-14
The Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 486, 207–214 (2012).
Caporaso, J. G. et al. Moving pictures of the human microbiome. Genome Biol. 12, R50 (2011).
pubmed: 21624126 pmcid: 3271711 doi: 10.1186/gb-2011-12-5-r50
Zaura, E., Keijser, B. J., Huse, S. M. & Crielaard, W. Defining the healthy” core microbiome” of oral microbial communities. BMC Microbiol. 9, (2009).
Moore, W. E. C. & Moore, L. V. H. The bacteria of periodontal diseases. Periodontol 2000 5, 66–77 (1994).
pubmed: 9673163 doi: 10.1111/j.1600-0757.1994.tb00019.x
Aßhauer, K. P., Wemheuer, B., Daniel, R. & Meinicke, P. Tax4Fun: predicting functional profiles from metagenomic 16S rRNA data. Bioinformatics 31, 2882–2884 (2015).
pubmed: 25957349 pmcid: 4547618 doi: 10.1093/bioinformatics/btv287
Wemheuer, F. et al. Tax4Fun2: prediction of habitat-specific functional profiles and functional redundancy based on 16S rRNA gene sequences. Environ. Microbiome 15, 11 (2020).
pubmed: 33902725 pmcid: 8067651 doi: 10.1186/s40793-020-00358-7
Simillion, C., Liechti, R., Lischer, H. E. L., Ioannidis, V. & Bruggmann, R. Avoiding the pitfalls of gene set enrichment analysis with SetRank. BMC Bioinforma. 18, 151 (2017).
doi: 10.1186/s12859-017-1571-6
Dieterle, F., Ross, A., Schlotterbeck, G. & Senn, H. Probabilistic Quotient Normalization as Robust Method to Account for Dilution of Complex Biological Mixtures. Application in 1H NMR Metabonomics. Anal. Chem. 78, 4281–4290 (2006).
pubmed: 16808434 doi: 10.1021/ac051632c
Bro, R. Multiway calibration. Multilinear PLS. J. Chemom. 10, 47–61 (1996).
doi: 10.1002/(SICI)1099-128X(199601)10:1<47::AID-CEM400>3.0.CO;2-C
Acar, E. et al. Structure-revealing data fusion. BMC Bioinforma. 15, 239 (2014).
doi: 10.1186/1471-2105-15-239
Acar, E., Bro, R. & Smilde, A. Data Fusion in Metabolomics Using Coupled Matrix and Tensor Factorizations. Proc. IEEE 103, 1602 (2015).
doi: 10.1109/JPROC.2015.2438719
Singh, A. P. & Gordon, G. J. Relational learning via collective matrix factorization. in Proceedings of the 14th ACM SIGKDD international conference on Knowledge discovery and data mining 650–658 (Association for Computing Machinery, New York, NY, USA, 2008). https://doi.org/10.1145/1401890.1401969 .
Anderson, A. C. et al. In-vivo shift of the microbiota in oral biofilm in response to frequent sucrose consumption. Sci. Rep. 8, 14202 (2018).
pubmed: 30242260 pmcid: 6155074 doi: 10.1038/s41598-018-32544-6
Schoilew, K. et al. Bacterial biofilm composition in healthy subjects with and without caries experience. J. Oral. Microbiol. 11, 1633194 (2019).
pubmed: 31275531 pmcid: 6598481 doi: 10.1080/20002297.2019.1633194
Thomas, A. M. et al. Alcohol and tobacco consumption affects bacterial richness in oral cavity mucosa biofilms. BMC Microbiol. 14, 250 (2014).
pubmed: 25278091 pmcid: 4186948 doi: 10.1186/s12866-014-0250-2
Baker, J. L., Bor, B., Agnello, M., Shi, W. & He, X. Ecology of the Oral Microbiome: Beyond Bacteria. Trends Microbiol. 25, 362–374 (2017).
pubmed: 28089325 pmcid: 5687246 doi: 10.1016/j.tim.2016.12.012
Nobbs, A. H. & Jenkinson, H. F. Interkingdom networking within the oral microbiome. Microbes Infect. 17, 484–492 (2015).
pubmed: 25805401 pmcid: 4485937 doi: 10.1016/j.micinf.2015.03.008
Fontaine, L. et al. A Novel Pheromone Quorum-Sensing System Controls the Development of Natural Competence in Streptococcus thermophilus and Streptococcus salivarius. J. Bacteriol. 192, 1444–1454 (2010).
pubmed: 20023010 doi: 10.1128/JB.01251-09
Gardan, R., Besset, C., Guillot, A., Gitton, C. & Monnet, V. The Oligopeptide Transport System Is Essential for the Development of Natural Competence in Streptococcus thermophilus Strain LMD-9. J. Bacteriol. 191, 4647–4655 (2009).
pubmed: 19447907 pmcid: 2704715 doi: 10.1128/JB.00257-09
Hammer, B. K. & Bassler, B. L. Quorum sensing controls biofilm formation in Vibrio cholerae. Mol. Microbiol. 50, 101–104 (2003).
pubmed: 14507367 doi: 10.1046/j.1365-2958.2003.03688.x
Kong, K.-F., Vuong, C. & Otto, M. Staphylococcus quorum sensing in biofilm formation and infection. Int. J. Med. Microbiol. 296, 133–139 (2006).
pubmed: 16487744 doi: 10.1016/j.ijmm.2006.01.042
Preda, V. G. & Săndulescu, O. Communication is the key: biofilms, quorum sensing, formation and prevention. Discoveries 7, (2019).
Chen, M. et al. Oxidative stress‐related biomarkers in saliva and gingival crevicular fluid associated with chronic periodontitis: A systematic review and meta‐analysis. J. Clin. Periodontol. 46, 608–622 (2019).
pubmed: 30989678 doi: 10.1111/jcpe.13112
Loesche, W. J. Oxygen Sensitivity of Various Anaerobic Bacteria. Appl. Microbiol. 18, 723–727 (1969).
pubmed: 5370458 pmcid: 378078 doi: 10.1128/am.18.5.723-727.1969
D’souza, L. L., Lawande, S. A., Samuel, J. & Pinto, M. J. W. Effect of salivary urea, pH and ureolytic microflora on dental calculus formation and its correlation with periodontal status. J. Oral. Biol. Craniofacial Res. 13, 8–12 (2023).
doi: 10.1016/j.jobcr.2022.10.004
Gaál Kovalčíková, A. et al. Urea and creatinine levels in saliva of patients with and without periodontitis. Eur. J. Oral. Sci. 127, 417–424 (2019).
pubmed: 31247131 doi: 10.1111/eos.12642
Nascimento, M. M., Gordan, V. V., Garvan, C. W., Browngardt, C. M. & Burne, R. A. Correlations of oral bacterial arginine and urea catabolism with caries experience. Oral. Microbiol. Immunol. 24, 89–95 (2009).
pubmed: 19239634 pmcid: 2742966 doi: 10.1111/j.1399-302X.2008.00477.x
Osmani, F. Can the salivary urea and stimulated saliva concentration be a marker of periodontal diseases in opioid users? A case-control study. Heliyon 9, (2023).
Bentley, C. D. & Disney, J. A. A comparison of partial and full mouth scoring of plaque and gingivitis in oral hygiene studies. J. Clin. Periodontol. 22, 131–135 (1995).
pubmed: 7775669 doi: 10.1111/j.1600-051X.1995.tb00124.x
Heinrich-Weltzien, R., Kühnisch, J., Van Der Veen, M., De Josselin De Jong, E. & Stößer, L. Quantitative light-induced fluorescence (QLF) - A potential method for the dental practitioner. Quintessence Int 34, 181–188 (2003).
pubmed: 12731599
Volgenant, C. M. C. et al. Red fluorescence of dental plaque in children —A cross-sectional study. J. Dent. 58, 40–47 (2017).
pubmed: 28115186 doi: 10.1016/j.jdent.2017.01.007
Zaura, E. et al. On the ecosystemic network of saliva in healthy young adults. ISME J. 11, 1218–1231 (2017).
pubmed: 28072421 pmcid: 5475835 doi: 10.1038/ismej.2016.199
Kozich, J. J., Westcott, S. L., Baxter, N. T., Highlander, S. K. & Schloss, P. D. Development of a Dual-Index Sequencing Strategy and Curation Pipeline for Analyzing Amplicon Sequence Data on the MiSeq Illumina Sequencing Platform. Appl. Environ. Microbiol. 79, 5112–5120 (2013).
pubmed: 23793624 pmcid: 3753973 doi: 10.1128/AEM.01043-13
Callahan, B. J. et al. DADA2: High-resolution sample inference from Illumina amplicon data. Nat. Methods 13, 581–583 (2016).
pubmed: 27214047 pmcid: 4927377 doi: 10.1038/nmeth.3869
Evans, A. M., DeHaven, C. D., Barrett, T., Mitchell, M. & Milgram, E. Integrated, Nontargeted Ultrahigh Performance Liquid Chromatography/Electrospray Ionization Tandem Mass Spectrometry Platform for the Identification and Relative Quantification of the Small-Molecule Complement of Biological Systems. Anal. Chem. 81, 6656–6667 (2009).
pubmed: 19624122 doi: 10.1021/ac901536h
Lawton, K. A. et al. Analysis of the adult human plasma metabolome. Pharmacogenomics 9, 383–397 (2008).
pubmed: 18384253 doi: 10.2217/14622416.9.4.383
Kanehisa, M., Furumichi, M., Sato, Y., Ishiguro-Watanabe, M. & Tanabe, M. KEGG: integrating viruses and cellular organisms. Nucleic Acids Res. 49, D545–D551 (2021).
pubmed: 33125081 doi: 10.1093/nar/gkaa970
Kanehisa, M. & Goto, S. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res. 28, 27–30 (2000).
pubmed: 10592173 pmcid: 102409 doi: 10.1093/nar/28.1.27
Silness, J. & Löe, H. Periodontal Disease in Pregnancy II. Correlation Between Oral Hygiene and Periodontal Condition. Acta Odontol. Scand. 22, 121–135 (1964).
pubmed: 14158464 doi: 10.3109/00016356408993968
Van der Weijden, G. A., Timmerman, M. F., Nijboer, A., Lie, M. A. & Van der Velden, U. A comparative study of electric toothbrushes for the effectiveness of plaque removal in relation to toothbrushing duration: Timerstudy. J. Clin. Periodontol. 20, 476–481 (1993).
pubmed: 8354721 doi: 10.1111/j.1600-051X.1993.tb00394.x
Aitchison, J. The Statistical Analysis of Compositional Data. J. R. Stat. Soc. Ser. B Methodol. 44, 139–160 (1982).
doi: 10.1111/j.2517-6161.1982.tb01195.x
Gloor, G. B., Macklaim, J. M., Pawlowsky-Glahn, V. & Egozcue, J. J. Microbiome Datasets Are Compositional: And This Is Not Optional. Front. Microbiol. 8, 2224 (2017).
pubmed: 29187837 pmcid: 5695134 doi: 10.3389/fmicb.2017.02224
Bro, R. & Smilde, A. K. Centering and scaling in component analysis. J. Chemom. 17, 16–33 (2003).
doi: 10.1002/cem.773
Chen, T. et al. The Human Oral Microbiome Database: a web accessible resource for investigating oral microbe taxonomic and genomic information. Database 2010, (2010).
Buchfink, B., Xie, C. & Huson, D. H. Fast and sensitive protein alignment using DIAMOND. Nat. Methods 12, 59–60 (2015).
pubmed: 25402007 doi: 10.1038/nmeth.3176
Martin, M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet J. 17, 10–12 (2011).
doi: 10.14806/ej.17.1.200
Kawashima, S., Katayama, T., Sato, Y. & Kanehisa, M. KEGG API: A Web Service Using SOAP/WSDL to Access the KEGG System. Genome Inf. 14, 673–674 (2003).
Martino, C. et al. Context-aware dimensionality reduction deconvolutes gut microbial community dynamics. Nat. Biotechnol. 39, 165–168 (2021).
pubmed: 32868914 doi: 10.1038/s41587-020-0660-7
van der Ploeg, G. R., Westerhuis, J. A., Heintz-Buschart, A. & Smilde, A. K. parafac4microbiome: Exploratory analysis of longitudinal microbiome data using Parallel Factor Analysis. Preprint at https://doi.org/10.1101/2024.05.02.592191 (2024).
Lorho, G., Westad, F. & Bro, R. Generalized correlation loadings: Extending correlation loadings to congruence and to multi-way models. Chemom. Intell. Lab. Syst. 84, 119–125 (2006).
doi: 10.1016/j.chemolab.2006.04.023
Borchers, H. W. & Borchers, M. H. W. Package ‘pracma’. Accessed On 4, (2022).
Schmidt, E. Über die Auflösung Linearer Gleichungen mit Unendlich Vielen Unbekannten. in Integralgleichungen und Gleichungen mit unendlich vielen Unbekannten (ed. Pietsch, A.) 11 249–278 (Springer Vienna, Vienna, 1989).
Kiers, H. A. L. Some procedures for displaying results from three-way methods. J. Chemom. 14, 151–170 (2000).
doi: 10.1002/1099-128X(200005/06)14:3<151::AID-CEM585>3.0.CO;2-G
Maechler, M. Finding groups in data: Cluster analysis extended Rousseeuw et al. R. Package Version 2, 242–248 (2019).
Kassambara, A. & Mundt, F. Package ‘factoextra’. Extr. Vis. Results Multivar. Data Anal. 76, (2017).

Auteurs

G R van der Ploeg (GR)

Biosystems Data Analysis, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.

B W Brandt (BW)

Preventive Dentistry, Academic Centre for Dentistry, Vrije Universiteit Amsterdam and University of Amsterdam, Amsterdam, The Netherlands.

B J F Keijser (BJF)

Microbiology and Systems Biology, TNO Healthy Living and Work, Leiden, The Netherlands.

M H van der Veen (MH)

Preventive Dentistry, Academic Centre for Dentistry, Vrije Universiteit Amsterdam and University of Amsterdam, Amsterdam, The Netherlands.
Paediatric Dentistry, Academic Centre for Dentistry, Vrije Universiteit Amsterdam and University of Amsterdam, Amsterdam, The Netherlands.

C M C Volgenant (CMC)

Preventive Dentistry, Academic Centre for Dentistry, Vrije Universiteit Amsterdam and University of Amsterdam, Amsterdam, The Netherlands.
Cariology, Academic Centre for Dentistry, Vrije Universiteit Amsterdam and University of Amsterdam, Amsterdam, The Netherlands.

E Zaura (E)

Preventive Dentistry, Academic Centre for Dentistry, Vrije Universiteit Amsterdam and University of Amsterdam, Amsterdam, The Netherlands.

A K Smilde (AK)

Biosystems Data Analysis, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.

J A Westerhuis (JA)

Biosystems Data Analysis, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.

A Heintz-Buschart (A)

Biosystems Data Analysis, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands. a.u.s.heintzbuschart@uva.nl.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH