Skip to main content

Advertisement

Log in

Shedding light on confounding factors likely to affect salivary infrared biosignatures

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Total human saliva is a biofluid which can be considered as a “mirror” reflecting the state of the body’s health. The “spectral mid-infrared fingerprint” represents a snapshot of the intrinsic biomolecular composition of a saliva sample translating multiple information about the patient, and likely to be related not only to his physiopathological status but also to his behavioral habits or even current medical treatments. These different patient-related characteristics are “confounding factors,” which may strongly affect the infrared data of salivary samples and disrupt the search for specific salivary biomarkers in the detection of diseases, especially in the case of complex pathologies influenced by multiple risk factors such as genetic factors and behavioral factors, and also other comorbidities. In this study, dealing with the processing of infrared saliva spectra from 56 patients, our aim was to highlight spectral features associated with some patient characteristics, namely tobacco smoking, periodontal diseases, and gender. By using multivariate statistical methods of feature selection (principal component analysis coupled with Kruskal–Wallis test, linear discriminant analysis coupled with randfeatures function), we were able to identify the discriminant vibrations associated with a specific factor and to assess the related spectral variability. Based on the methodology demonstrated here, it could be very valuable in the future to develop processing aimed at neutralizing these variabilities, in order to determine specific spectroscopic markers related to a multifactorial disease for diagnostic or follow-up purposes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Schafer CA, Schafer JJ, Yakob M, Lima P, Camargo P, Wong DTW. Saliva diagnostics: utilizing oral fluids to determine health status. Monogr Oral Sci. 2014;24:88–98.

    Article  PubMed  Google Scholar 

  2. Beale D, Jones O, Karpe A, Dayalan S, Oh D, Kouremenos K, et al. A review of analytical techniques and their application in disease diagnosis in breathomics and salivaomics research. Int J Mol Sci. 2016;18:24.

    Article  CAS  PubMed Central  Google Scholar 

  3. Kaczor-Urbanowicz KE, Martin Carreras-Presas C, Aro K, Tu M, Garcia-Godoy F, Wong DT. Saliva diagnostics – current views and directions. Exp Biol Med. 2017;242:459–72.

    Article  CAS  Google Scholar 

  4. Wang X, Kaczor-Urbanowicz KE, Wong DTW. Salivary biomarkers in cancer detection. Med Oncol Northwood Lond Engl. 2017;34:7.

    Article  CAS  Google Scholar 

  5. Wang A, Wang C, Tu M, Wong D. Oral biofluid biomarker research: current status and emerging frontiers. Diagnostics. 2016;6:45.

    Article  CAS  PubMed Central  Google Scholar 

  6. Lawrence HP. Salivary markers of systemic disease: noninvasive diagnosis of disease and monitoring of general health. J Can Dent Assoc. 2002;68:170–4.

    PubMed  Google Scholar 

  7. Baker MJ, Hussain SR, Lovergne L, Untereiner V, Hughes C, Lukaszewski RA, et al. Developing and understanding biofluid vibrational spectroscopy: a critical review. Chem Soc Rev. 2016;45:1803–18.

    Article  CAS  PubMed  Google Scholar 

  8. Kuku G, Saricam M, Akhatova F, Danilushkina A, Fakhrullin R, Culha M. Surface-enhanced Raman scattering to evaluate nanomaterial cytotoxicity on living cells. Anal Chem. 2016;88:9813–20.

    Article  CAS  PubMed  Google Scholar 

  9. Gowen AA, Feng Y, Gaston E, Valdramidis V. Recent applications of hyperspectral imaging in microbiology. Talanta. 2015;137:43–54.

    Article  CAS  PubMed  Google Scholar 

  10. Petrich W, Lewandrowski KB, Muhlestein JB, Hammond MEH, Januzzi JL, Lewandrowski EL, et al. Potential of mid-infrared spectroscopy to aid the triage of patients with acute chest pain. Analyst. 2009;134:1092.

    Article  CAS  PubMed  Google Scholar 

  11. Khaustova S, Shkurnikov M, Tonevitsky E, Artyushenko V, Tonevitsky A. Noninvasive biochemical monitoring of physiological stress by Fourier transform infrared saliva spectroscopy. Analyst. 2010;135:3183.

    Article  CAS  PubMed  Google Scholar 

  12. Simsek Ozek N, Zeller I, Renaud DE, Gümüş P, Nizam N, Severcan F, et al. Differentiation of chronic and aggressive periodontitis by FTIR spectroscopy. J Dent Res. 2016;95:1472–8.

    Article  CAS  PubMed  Google Scholar 

  13. Bottoni U, Tiriolo R, Pullano SA, Dastoli S, Amoruso GF, Nistico SP, et al. Infrared saliva analysis of psoriatic and diabetic patients: similarities in protein components. IEEE Trans Biomed Eng. 2016;63:379–84.

    Article  PubMed  Google Scholar 

  14. Armenta S, Garrigues S, de la Guardia M, Brassier J, Alcalà M, Blanco M. Analysis of ecstasy in oral fluid by ion mobility spectrometry and infrared spectroscopy after liquid–liquid extraction. J Chromatogr A. 2015;1384:1–8.

    Article  CAS  PubMed  Google Scholar 

  15. Rodrigues LM, Magrini TD, Lima CF, Scholz J, da Silva Martinho H, Almeida JD. Effect of smoking cessation in saliva compounds by FTIR spectroscopy. Spectrochim Acta A Mol Biomol Spectrosc. 2017;174:124–9.

    Article  CAS  PubMed  Google Scholar 

  16. Diem M. Comments on recent reports on infrared spectral detection of disease markers in blood components. J Biophotonics. 2018;11:e201800064.

    Article  CAS  PubMed  Google Scholar 

  17. Schane RE, Glantz SA, Ling PM. Social smoking. Am J Prev Med. 2009;37:124–31.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Caton J G, Armitage G, Berglundh T, Chapple ILC, Jepsen S, Kornman K S, et al. A new classification scheme for periodontal and peri-implant diseases and conditions - introduction and key changes from the 1999 classification. J Clin Periodontol. 2018;45:S1–8.

    Article  Google Scholar 

  19. Untereiner V, Dhruvananda Sockalingum G, Garnotel R, Gobinet C, Ramaholimihaso F, Ehrhard F, et al. Bile analysis using high-throughput FTIR spectroscopy for the diagnosis of malignant biliary strictures: a pilot study in 57 patients: spectral diagnosis of malignant biliary strictures. J Biophotonics. 2014;7:241–53.

    Article  CAS  PubMed  Google Scholar 

  20. Helm D, Labischinski H, Naumann D. Elaboration of a procedure for identification of bacteria using Fourier-transform IR spectral libraries: a stepwise correlation approach. J Microbiol Methods. 1991;14:127–42.

    Article  Google Scholar 

  21. Afseth NK, Kohler A. Extended multiplicative signal correction in vibrational spectroscopy, a tutorial. Chemom Intell Lab Syst. 2012;117:92–9.

    Article  CAS  Google Scholar 

  22. Abdi H, Williams LJ. Principal component analysis: principal component analysis. Wiley Interdiscip Rev Comput Stat. 2010;2:433–59.

    Article  Google Scholar 

  23. Eklouh-Molinier C, Happillon T, Bouland N, Fichel C, Diébold M-D, Angiboust J-F, et al. Investigating the relationship between changes in collagen fiber orientation during skin aging and collagen/water interactions by polarized-FTIR microimaging. Analyst. 2015;140:6260–8.

    Article  CAS  PubMed  Google Scholar 

  24. Schultz CP, Ahmed MK, Dawes C, Mantsch HH. Thiocyanate levels in human saliva: quantitation by Fourier transform infrared spectroscopy. Anal Biochem. 1996;240:7–12.

    Article  CAS  PubMed  Google Scholar 

  25. Takamura A, Watanabe K, Akutsu T, Ozawa T. Soft and robust identification of body fluid using Fourier transform infrared spectroscopy and chemometric strategies for forensic analysis. Sci Rep. 2018;8:8459.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Aggarwal A, Keluskar V, Goyal R, Dahiya P. Salivary thiocyanate: a biochemical indicator of cigarette smoking in adolescents. Oral Health Prev Dent. 2013;11:221–7.

    PubMed  Google Scholar 

  27. Popa C. Infrared spectroscopy study of the influence of inhaled vapors/smoke produced by cigarettes of active smokers. J Biomed Opt. 2014;20:051003.

    Article  CAS  Google Scholar 

  28. Xiang XM, Liu KZ, Man A, Ghiabi E, Cholakis A, Scott DA. Periodontitis-specific molecular signatures in gingival crevicular fluid. J Periodontal Res. 2010;45:345–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Panjamurthy K, Manoharan S, Ramachandran CR. Lipid peroxidation and antioxidant status in patients with periodontitis. Cell Mol Biol Lett. 2005;10:255–64.

    CAS  PubMed  Google Scholar 

  30. Clifton S, Macdowall W, Copas AJ, Tanton C, Keevil BG, Lee DM, et al. Salivary testosterone levels and health status in men and women in the British general population: findings from the Third National Survey of Sexual Attitudes and Lifestyles (Natsal-3). J Clin Endocrinol Metab. 2016;101:3939–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Muro CK, de Souza Fernandes L, Lednev IK. Sex determination based on Raman spectroscopy of saliva traces for forensic purposes. Anal Chem. 2016;88:12489–93.

    Article  CAS  PubMed  Google Scholar 

  32. Miller VM. Why are sex and gender important to basic physiology and translational and individualized medicine? Am J Physiol Heart Circ Physiol. 2014;306:H781–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. García-Blanco A, Vento M, Diago V, Cháfer-Pericás C. Reference ranges for cortisol and α-amylase in mother and newborn saliva samples at different perinatal and postnatal periods. J Chromatogr B Anal Technol Biomed Life Sci. 2016;1022:249–55.

    Article  CAS  Google Scholar 

  34. Steiner G, Bartels T, Stelling A, Krautwald-Junghanns M-E, Fuhrmann H, Sablinskas V, et al. Gender determination of fertilized unincubated chicken eggs by infrared spectroscopic imaging. Anal Bioanal Chem. 2011;400:2775–82.

    Article  CAS  PubMed  Google Scholar 

  35. Chee B, Park B, Bartold PM. Periodontitis and type II diabetes: a two-way relationship. Int J Evid Based Healthc. 2013;11:317–29.

    Article  PubMed  Google Scholar 

  36. Kohorst JJ, Kimball AB, Davis MDP. Systemic associations of hidradenitis suppurativa. J Am Acad Dermatol. 2015;73:S27–35.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge the Association Française pour la Recherche sur l’Hidrosadénite (AFRH) and the Association Française d’Épargne et de Retraite (AFER).

The authors thank Dr. Marie-Pascale Hippolyte, University Hospital of Reims, for improving the English presentation of this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Olivier Piot.

Ethics declarations

This study was approved by the French Ethics Committee for the Protection of Individuals Consenting to Biomedical Research (No. 18019), by the French National Agency for Medicines and Health Products Safety (2018-A0016451), and by ClinicalTrials.gov (NCT03553888).

Conflict of interest

The authors declare that they have no conflict to declare.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Derruau, S., Gobinet, C., Mateu, A. et al. Shedding light on confounding factors likely to affect salivary infrared biosignatures. Anal Bioanal Chem 411, 2283–2290 (2019). https://doi.org/10.1007/s00216-019-01669-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-019-01669-6

Keywords

Navigation