High-throughput proteomic analysis of candidate biomarker changes in gingival crevicular fluid after treatment of chronic periodontitis
Open accessAbstract
Background and Objective: Untargeted, high‐throughput proteomics methodologies have great potential to aid in identifying biomarkers for the diagnosis of periodontal disease. The application of such methods to the discovery of candidate biomarkers for the resolution of periodontal inflammation after periodontal therapy has been investigated. Material and Methods: Gingival crevicular fluid samples were collected from 10 patients diagnosed with chronic periodontitis at baseline and 1, 5, 9 and 13 weeks after completion of mechanical periodontal treatment. Clinical indices of periodontal disease, including probing depth, recession, clinical attachment level and bleeding on probing, were recorded at baseline and 13 weeks. Samples were analyzed using an online liquid chromatography‐nanoelectrospray‐hybrid ion trap‐Orbitrap mass spectrometer. Spectra were processed with the PILOT _ PROTEIN proteomics software suite. Results: Clinical parameters were significantly improved 13 weeks after treatment (Wilcoxon signed ranks test, P < .05). From the substantial number of identified proteins, a small subset was extracted by filter methods that included temporal pattern matching, logistic function fitting and mixed‐integer linear optimization. This subset includes azurocidin, lysozyme C and myosin‐9 as candidate biomarkers prominent at baseline and alpha‐smooth muscle actin as prominent 13 weeks after treatment. Cross‐validation studies yielded average predictive accuracy and area under the curve of 0.900 and 0.930, respectively. Conclusion: High‐throughput proteomic analysis can contribute to identifying endpoints of periodontal therapy. These candidate biomarkers should be evaluated for clinical efficacy.
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Cites
Cortes, C., & Vapnik, V. (1995) · Machine Learning · doi:10.1007/bf00994018 · Cited by 59,421 · see citing works
The Nature of Statistical Learning Theory
Vapnik, V. N. (1995) · doi:10.1007/978-1-4757-2440-0 · Cited by 39,138 · see citing works
The meaning and use of the area under a receiver operating characteristic (ROC) curve.
Hanley, J. A., & McNeil, B. J. (1982) · Radiology · doi:10.1148/radiology.143.1.7063747 · Cited by 21,856 · see citing works
Libsvm : A library for support vector machines
Ferrari, V. (2008) · Medical Entomology and Zoology · Cited by 10,124 · see citing works
Development of a Classification System for Periodontal Diseases and Conditions
Armitage, G. C. (1999) · Annals of Periodontology · doi:10.1902/annals.1999.4.1.1 · Cited by 5,110 · see citing works
Microbial complexes in subgingival plaque
Socransky, S. S., Haffajee, A. D., Cugini, M. A., Smith, C., & Kent, R. L. (1998) · Journal of Clinical Periodontology · doi:10.1111/j.1600-051x.1998.tb02419.x · Cited by 5,050 · see citing works
A cross-platform toolkit for mass spectrometry and proteomics
Chambers, M., MacLean, B., Burke, R., Amodei, D., Ruderman, D., Neumann, S., Gatto, L., Fischer, B., Pratt, B. S., Egertson, J. D., et al. (2012) · Nature Biotechnology · doi:10.1038/nbt.2377 · Cited by 4,038 · see citing works
Alpha-Smooth Muscle Actin Expression Upregulates Fibroblast Contractile Activity
Hinz, B., Celetta, G., Tomasek, J. J., Gabbiani, G., & Chaponnier, C. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.9.2730 · Cited by 1,288 · see citing works
A guided tour of the Trans‐Proteomic Pipeline
Deutsch, E. W., Mendoza, L., Shteynberg, D. D., Farrah, T., Lam, H., Tasman, N., Sun, Z., Nilsson, E. J., Pratt, B. S., Prazen, B. J., et al. (2010) · PROTEOMICS · doi:10.1002/pmic.200900375 · Cited by 746 · see citing works
Tonetti, M. S., Claffey, N. M., & on behalf of the European Workshop in Periodontology group C (2005) · Journal Of Clinical Periodontology · doi:10.1111/j.1600-051x.2005.00822.x · Cited by 617 · see citing works
Are peri‐implantitis lesions different from periodontitis lesions?
Berglundh, T., Zitzmann, N. U., & Donati, M. (2011) · Journal Of Clinical Periodontology · doi:10.1111/j.1600-051x.2010.01672.x · Cited by 363 · see citing works
Buduneli, N., & Kinane, D. F. (2011) · Journal Of Clinical Periodontology · doi:10.1111/j.1600-051x.2010.01670.x · Cited by 348 · see citing works
Dependence of collagen remodelling on α‐smooth muscle actin expression by fibroblasts
Arora, P. D., & McCulloch, C. A. (1994) · Journal of Cellular Physiology · doi:10.1002/jcp.1041590120 · Cited by 276 · see citing works
Origin and function of the cellular components in gingival crevice fluid
Delima, A. J., & Dyke, T. E. V. (2003) · Periodontology 2000 · doi:10.1034/j.1600-0757.2003.03105.x · Cited by 258 · see citing works
Regulation of Smooth Muscle Actin Expression and Contraction in Adult Human Mesenchymal Stem Cells
Kinner, B., Zaleskas, J. M., & Spector, M. (2002) · Experimental Cell Research · doi:10.1006/excr.2002.5561 · Cited by 233 · see citing works
Campanelli, D., Detmers, P., Nathan, C., & Gabay, J. E. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114518 · Cited by 216 · see citing works
The clinical value of salivary biomarkers for periodontal disease.
Zhang, L., Henson, B., Camargo, P., & Wong, D. (2009) · Periodontology 2000 · doi:10.1111/j.1600-0757.2009.00315.x · Cited by 172 · see citing works
Host-derived diagnostic markers for periodontitis: do they exist in gingival crevice fluid?
Loos, B., & Tjoa, S. T. (2005) · Periodontology 2000 · doi:10.1111/j.1600-0757.2005.00129.x · Cited by 164 · see citing works
Functional Characteristics of Gingival and Periodontal Ligament Fibroblasts
Giannopoulou, C., & Cimasoni, G. (1996) · Journal of Dental Research · doi:10.1177/00220345960750030601 · Cited by 156 · see citing works
Bostancı, N., Heywood, W., Mills, K. A., Parkar, M. H., Nibali, L., & Donos, N. (2010) · Journal of Proteome Research · doi:10.1021/pr900941z · Cited by 145 · see citing works
Facts and artifacts in proteomics of body fluids. What proteomics of saliva is telling us?
Messana, I., Inzitari, R., Fanali, C., Cabras, T., & Castagnola, M. (2008) · Journal of Separation Science · doi:10.1002/jssc.200800100 · Cited by 140 · see citing works
Leppilahti, J. M., Hernández‐Ríos, P. A., Gamonal, J. A., Tervahartiala, T., Brignardello‐Petersen, R., Mantyla, P., Sorsa, T., & Hernández, M. (2014) · Journal of Clinical Periodontology · doi:10.1111/jcpe.12223 · Cited by 138 · see citing works
Baliban, R. C., Sakellari, D., Li, Z., DiMaggio, P. A., Garcia, B. A., & Floudas, C. A. (2011) · Journal Of Clinical Periodontology · doi:10.1111/j.1600-051x.2011.01805.x · Cited by 99 · see citing works
Self-citationAge-Dependent Modifications of the Human Salivary Secretory Protein Complex
Cabras, T., Pisano, E., Boi, R., Olianas, A., Manconi, B., Inzitari, R., Fanali, C., Giardina, B., Castagnola, M., & Messana, I. (2009) · Journal of Proteome Research · doi:10.1021/pr900212u · Cited by 94 · see citing works
Deep metaproteomic analysis of human salivary supernatant
Jagtap, P. D., McGowan, T. F., Bandhakavi, S., Tu, Z. J., Seymour, S. L., Griffin, T. J., & Rudney, J. D. (2012) · PROTEOMICS · doi:10.1002/pmic.201100503 · Cited by 92 · see citing works
The salivary proteome: Challenges and perspectives
Siqueira, W. L., & Dawes, C. (2011) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.201100046 · Cited by 89 · see citing works
Lysozyme and Lactoferrin Quantitation in the Crevicular Fluid
Friedman, S. A., Mandel, I. D., & Herrera, M. S. (1983) · Journal of Periodontology · doi:10.1902/jop.1983.54.6.347 · Cited by 88 · see citing works
Antimicrobial peptides and proteins, exercise and innate mucosal immunity
West, N. P., Pyne, D. B., Renshaw, G. M. C., & Cripps, A. W. (2006) · FEMS Immunology & Medical Microbiology · doi:10.1111/j.1574-695x.2006.00132.x · Cited by 84 · see citing works
Mass Spectrometric Analyses of Peptides and Proteins in Human Gingival Crevicular Fluid
Ngo, L. H., Veith, P. D., Chen, Y.-Y., Chen, D., Darby, I. B., & Reynolds, E. C. (2010) · Journal of Proteome Research · doi:10.1021/pr900775s · Cited by 82 · see citing works
Jentsch, H. F. R., Sievert, Y., & Göcke, R. (2004) · Journal Of Clinical Periodontology · doi:10.1111/j.1600-051x.2004.00512.x · Cited by 75 · see citing works
Plasminogen binding by oral streptococci from dental plaque and inflammatory lesions
Kinnby, B., Booth, N. A., & Svensäter, G. (2008) · Microbiology · doi:10.1099/mic.0.2007/013235-0 · Cited by 74 · see citing works
Choi, Y.-J., Heo, S.-H., Lee, J.-M., & Cho, J.-Y. (2011) · Proteome Science · doi:10.1186/1477-5956-9-42 · Cited by 71 · see citing works
Analysis of proteins in human gingival crevicular fluid by mass spectrometry
Kido, J., Bando, M., Hiroshima, Y., Iwasaka, H., Yamada, K., Ohgami, N., Nambu, T., Kataoka, M., Yamamoto, T., Shinohara, Y., et al. (2012) · Journal of Periodontal Research · doi:10.1111/j.1600-0765.2011.01458.x · Cited by 66 · see citing works
Bostancı, N., Ramberg, P., Wåhlander, Å., Grossman, J., Jönsson, D., Barnes, V. M., & Papapanou, P. N. (2012) · Journal of Proteome Research · doi:10.1021/pr300761e · Cited by 63 · see citing works
Contribution of proteomics to our understanding of periodontal inflammation
Bostancı, N., & Bao, K. (2016) · PROTEOMICS · doi:10.1002/pmic.201500518 · Cited by 62 · see citing works
Castagnola, M., Cabras, T., Iavarone, F., et al. (2012) · Expert Review of Proteomics · doi:10.1586/epr.11.77 · Cited by 61 · see citing works
Tsuchida, S., Satoh, M., Kawashima, Y., Sogawa, K., Kado, S., Sawai, S., Nishimura, M., Ogita, M., Takeuchi, Y., Kobyashi, H., et al. (2013) · PROTEOMICS · doi:10.1002/pmic.201200510 · Cited by 57 · see citing works
De Novo Peptide Identification via Tandem Mass Spectrometry and Integer Linear Optimization
DiMaggio, P. A., & Floudas, C. A. (2007) · Analytical Chemistry · doi:10.1021/ac0618425 · Cited by 55 · see citing works
Self-citationBaliban, R. C., DiMaggio, P. A., Plazas-Mayorca, M. D., et al. (2010) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m900487-mcp200 · Cited by 49 · see citing works
Almeida, R. P., Vanet, A., Witko-Sarsat, V., Melchior, M., McCabe, D., & Gabay, J. E. (1996) · Protein Expression and Purification · doi:10.1006/prep.1996.0053 · Cited by 46 · see citing works
Baliban, R. C., Sakellari, D., Li, Z., Guzman, Y. A., Garcia, B. A., & Floudas, C. A. (2012) · Journal Of Clinical Periodontology · doi:10.1111/jcpe.12037 · Cited by 40 · see citing works
Self-citationFletcher, J. M., Nair, S. P., Ward, J. M., et al. (2001) · Microbial Pathogenesis · doi:10.1006/mpat.2000.0439 · Cited by 37 · see citing works
Non‐bacterial protein expression in periodontal pockets by proteome analysis
Bertoldi, C., Bellei, E., Pellacani, C., Ferrari, D., Lucchi, A., Cuoghi, A., Bergamini, S., Cortellini, P., Tomasi, A., Zaffe, D., et al. (2012) · Journal Of Clinical Periodontology · doi:10.1111/jcpe.12050 · Cited by 37 · see citing works
Ngo, L., Darby, I. B., Veith, P. D., Locke, A. G., & Reynolds, E. C. (2012) · Journal of Periodontal Research · doi:10.1111/jre.12012 · Cited by 32 · see citing works
Proteomics for the discovery of biomarkers and diagnosis of periodontitis: a critical review
Guzman, Y. A., Sakellari, D., Arsenakis, M., & Floudas, C. A. (2013) · Expert Review of Proteomics · doi:10.1586/14789450.2014.864953 · Cited by 30 · see citing works
Self-citationPerera, S., SABIN, E. A., Nelson, P., & Lowe, D. (1998) · International Journal of Behavioral Medicine · doi:10.1207/s15327558ijbm0502_3 · Cited by 25 · see citing works
DiMaggio, P. A., Floudas, C. A., Lu, B., et al. (2008) · Journal of Proteome Research · doi:10.1021/pr700577z · Cited by 20 · see citing works
Self-citationBaliban, R. C., DiMaggio, P. A., Plazas-Mayorca, M. D., et al. (2012) · Journal of Proteome Research · doi:10.1021/pr300418j · Cited by 9 · see citing works
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Research works printed but not linked: 1
- [27]Guzman YA Theoretical advances in robust optimization, feature selection,and biomarker discovery 2016 Doctoral dissertation Princeton University
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Alarcón-Sánchez, M. A., Heboyan, A., Fernandes, G. V. D. O., Castro-Alarcón, N., & Romero-Castro, N. S. (2023) · Molecules · doi:10.3390/molecules28031075 · Cited by 52 · see citing works
Azurocidin in gingival crevicular fluid as a potential biomarker of chronic periodontitis
Nalmpantis, D., Gatou, A., Fragkioudakis, I., Margariti, A., Skoura, L., & Sakellari, D. (2020) · Journal of Periodontal Research · doi:10.1111/jre.12703 · Cited by 17 · see citing works
Self-citation
- Authors
- Guzman, Y. A., Sakellari, D., Papadimitriou, K., & Floudas, C. A.
- Affiliations
- Princeton University (US)
- Aristotle University of Thessaloniki (GR)
- Texas A&M University (US)
- Corresponding author
- Sakellari, D.
- Venue
- Journal of Periodontal Research
- Publisher
- Wiley
- Published
- 2018-06-14
- Volume
- 53
- Issue
- 5
- Pages
- 853-860
- ISSN
- 0022-3484 (ISSN-L)
- 1600-0765
- PMC
- PMC6135659
- OpenAlex
- W2807871813
- Cited by
- 29
- References
- 48
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 7 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 5 · 2019: 3
- FWCI
- 3.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Journal of Periodontal Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (r01lm009338)
- National Science Foundation (CBET‐0941143)
- Topics
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Health Sciences › Medicine › Urology › Periodontal Regeneration and Treatments
- Keywords
- chronic periodontitis, gingival crevicular fluid, biomarkers, periodontal treatment, heparin-binding protein, lysozyme C, myosin-9, alpha-smooth muscle actin, proteomic biomarker discovery, treatment endpoints
- MeSH terms
- Chromatography, Liquid, Female, Gingival Crevicular Fluid, Humans, Male, Middle Aged, Periodontal Index, Biomarkers, Spectrometry, Mass, Electrospray Ionization, Nanotechnology, Proteomics, Chronic Periodontitis
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