Machine Learning Assisted Handheld Confocal Raman Micro-Spectroscopy for Identification of Clinically Relevant Atopic Eczema Biomarkers
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Atopic dermatitis (AD) is a common chronic inflammatory skin dermatosis condition due to skin barrier dysfunction that causes itchy, red, swollen, and cracked skin. Currently, AD severity clinical scores are subjected to intra- and inter-observer differences. There is a need for an objective scoring method that is sensitive to skin barrier differences. The aim of this study was to evaluate the relevant skin chemical biomarkers in AD patients. We used confocal Raman micro-spectroscopy and advanced machine learning methods as means to classify eczema patients and healthy controls with sufficient sensitivity and specificity. Raman spectra at different skin depths were acquired from subjects’ lower volar forearm location using an in-house developed handheld confocal Raman micro-spectroscopy system. The Raman spectra corresponding to the skin surface from all the subjects were further analyzed through partial least squares discriminant analysis, a binary classification model allowing the classification between eczema and healthy subjects with a sensitivity and specificity of 0.94 and 0.85, respectively, using stratified K-fold (K = 10) cross-validation. The variable importance in the projection score from the partial least squares discriminant analysis classification model further elucidated the role of important stratum corneum proteins and lipids in distinguishing two subject groups.
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Handheld confocal Raman spectroscopy can classify patients with AD with spectroscopic signatures that depict stratum corneum proteins and lipids.
“Other promising modalities for classification include handheld confocal Raman spectroscopy, with one study classifying patients with AD with spectroscopic signatures that depict stratum corneum proteins and lipids (Dev et al, 2022)”
From Artificial intelligence–enabled precision medicine for inflammatory skin diseases (2026) · cites this paper as Dev et al, 2022
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Janssens, M., van Smeden, J., Gooris, G. S., Bras, W., Portale, G., Caspers, P. J., Vreeken, R. J., Hankemeier, T., Kezic, S., Wolterbeek, R., et al. (2012) · Journal of Lipid Research · doi:10.1194/jlr.p030338 · Cited by 488 · see citing works
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Research works printed but not linked: 29
- [1]Chung J. Simpson E.L. The socioeconomics of atopic dermatitis Ann. Allergy Asthma Immunol. 2019 122 360 366 10.1016/j.anai.2018.12.017 30597208 · DOI
- [2]Kok W.L. Yew Y.W. Thng T.G.S. A population-based cohort study of atopic eczema among young adult males in Singapore Int. J. Dermatol. 2018 57 e52 10.1111/ijd.14074 29888391 · DOI
- [3]Cheok S. Yee F. Ma J.Y.S. Leow R. Ho M.S.L. Yew Y.W. Tay Y.K. Rebello S.A. Luo N. Koh M.J.A. Prevalence and descriptive epidemiology of atopic dermatitis and its impact on quality of life in Singapore Br. J. Dermatol. 2018 178 276 277 10.1111/bjd.15587 28415136 · DOI
- [4]Cork M.J. Danby S.G. Vasilopoulos Y. Hadgraft J. Lane M.E. Moustafa M. Guy R.H. Macgowan A.L. Tazi-Ahnini R. Ward S.J. Epidermal barrier dysfunction in atopic dermatitis J. Investig. Dermatol. 2009 129 1892 1908 10.1038/jid.2009.133 19494826 · DOI
- [5]Jungersted J.M. Scheer H. Mempel M. Baurecht H. Cifuentes L. Høgh J.K. Hellgren L.I. Jemec G.B.E. Agner T. Weidinger S. Stratum corneum lipids, skin barrier function and filaggrin mutations in patients with atopic eczema Allergy 2010 65 911 918 10.1111/j.1398-9995.2010.02326.x 20132155 · DOI · Paper page
- [6]O’Regan G.M. Kemperman P.M. Sandilands A. Chen H. Campbell L.E. Kroboth K. Watson R. Rowland M. Puppels G.J. McLean W.H. Raman profiles of the stratum corneum define 3 filaggrin genotype–determined atopic dermatitis endophenotypes J. Allergy Clin. Immunol. 2010 126 574 580 10.1016/j.jaci.2010.04.038 20621340 PMC3627961 · DOI
- [7]Mlitz V. Latreille J. Gardinier S. Jdid R. Drouault Y. Hufnagl P. Eckhart L. Guinot C. Tschachler E. Impact of filaggrin mutations on Raman spectra and biophysical properties of the stratum corneum in mild to moderate atopic dermatitis J. Eur. Acad. Dermatol. Venereol. 2012 26 983 990 10.1111/j.1468-3083.2011.04198.x 21812836 · DOI
- [9]Janssens M. Van Smeden J. Puppels G.J. Lavrijsen A.P. Caspers P.J. Bouwstra J.A. Lipid to protein ratio plays an important role in the skin barrier function in patients with atopic eczema Br. J. Dermatol. 2014 170 1248 1255 10.1111/bjd.12908 24641443 · DOI
- [10]Verzeaux L. Vyumvuhore R. Boudier D. le Guillou M. Bordes S. Essendoubi M. Manfait M. Closs B. Atopic skin: In vivo Raman identification of global molecular signature, a comparative study with healthy skin Exp. Dermatol. 2018 27 403 408 10.1111/exd.13388 28603906 · DOI
- [11]Caspers P.J. Lucassen G.W. Wolthuis R. Bruining H.A. Puppels G.J. In vitro and in vivo Raman spectroscopy of human skin Biospectroscopy 1998 4 S31 S39 10.1002/(SICI)1520-6343(1998)4:5+<S31::AID-BSPY4>3.0.CO;2-M 9787912 · DOI
- [12]Caspers P.J. Lucassen G.W. Carter E.A. Bruining H.A. Puppels G.J. In vivo confocal Raman microspectroscopy of the skin: Noninvasive determination of molecular concentration profiles J. Investig. Dermatol. 2001 116 434 442 10.1046/j.1523-1747.2001.01258.x 11231318 · DOI
- [13]Caspers P.J. Lucassen G.W. Puppels G.J. Combined In Vivo Confocal Raman Spectroscopy and Confocal Microscopy of Human Skin Biophys. J. 2003 85 572 580 10.1016/S0006-3495(03)74501-9 12829511 PMC1303112 · DOI
- [14]Ho C.J.H. Yew Y.W. Dinish U.S. Kuan A.H.Y. Wong M.K.W. Bi R. Dev K. Li X. Singh G. Moothanchery M. Handheld confocal Raman spectroscopy (CRS) for objective assessment of skin barrier function and stratification of severity in atopic dermatitis (AD) patients J. Dermatol. Sci. 2020 98 20 25 10.1016/j.jdermsci.2020.02.001 32063461 · DOI
- [15]Rinnan Å. Pre-processing in vibrational spectroscopy—When, why and how Anal. Methods 2014 6 7124 7129 10.1039/C3AY42270D 40883930 · DOI
- [16]Liland K.H. Kohler A. Afseth N.K. Model-based pre-processing in Raman spectroscopy of biological samples J. Raman Spectrosc. 2016 47 643 650 10.1002/jrs.4886 · DOI
- [17]Boelens H.F. Dijkstra R.J. Eilers P.H. Fitzpatrick F. Westerhuis J.A. New background correction method for liquid chromatography with diode array detection, infrared spectroscopic detection and Raman spectroscopic detection J. Chromatogr. A 2004 10570 21 30 10.1016/j.chroma.2004.09.035 15584219 · DOI
- [18]Savitzky A. Golay M.J.E. Smoothing and Differentiation of Data by Simplified Least Squares Procedures Anal. Chem. 1964 36 1627 1639 10.1021/ac60214a047 · DOI · Paper page
- [19]Franzen L. Anderski J. Windbergs M. Quantitative detection of caffeine in human skin by confocal Raman spectroscopy-A systematic in vitro validation study Eur. J. Pharm. Biopharm. 2015 95 110 116 10.1016/j.ejpb.2015.03.026 25828208 · DOI
- [20]De Almeida M.R. Correa D.N. Rocha W.F.C. Scafi F.J.O. Poppi R.J. Discrimination between Authentic and Counterfeit Banknotes Using Raman Spectroscopy and PLS-DA with Uncertainty Estimation Microchem. J. 2013 109 170 177 10.1016/j.microc.2012.03.006 · DOI
- [21]Ballabio D. Consonnia V. Classification tools in chemistry. Part 1: Linear models. PLS-DA Anal. Methods 2013 5 3790 3798 10.1039/c3ay40582f · DOI
- [22]Brereton R.G. Lloyd G.R. Partial least squares discriminant analysis: Taking the magic away J. Chemom. 2014 28 213 225 10.1002/cem.2609 · DOI
- [23]Surmacki J.M. Woodhams B.J. Haslehurst A. Ponder B.A.J. Bohndiek S.E. Raman micro-spectroscopy for accurate identification of primary human bronchial epithelial cells Sci. Rep. 2018 8 12604 10.1038/s41598-018-30407-8 30135442 PMC6105656 · DOI
- [24]Chrit L. Hadjur C. Morel S. Sockalingum G. Lebourdon G. Leroy F. Manfait M. In vivo chemical investigation of human skin using a confocal Raman fiber optic microprobe J. Biomed. Opt. 2005 10 44007 10.1117/1.2003747 16178641 · DOI
- [25]Movasaghi Z. Rehman S. Rehman I.U. Raman Spectroscopy of Biological Tissues Appl. Spectrosc. Rev. 2007 42 493 541 10.1080/05704920701551530 · DOI · Paper page
- [26]Tfaili S. Gobinet C. Josse G. Angiboust J. Manfait M. Piot O. Confocal Raman microspectroscopy for skin characterization: A comparative study between human skin and pig skin Analyst 2012 137 3673 3682 10.1039/C2AN16292J 22754919 · DOI
- [27]Feng X. Moy A.J. Nguyen H.T.M. Zhang J. Fox M.C. Sebastian K.R. Reichenberg J.S. Markey M.K. Tunnell J.W. Raman active components of skin cancer Biomed. Opt. Express. 2017 8 2835 2850 10.1364/BOE.8.002835 28663910 PMC5480433 · DOI
- [28]Choe C. Schleusener J. Lademann J. Darvin M.E. Keratin-water-NMF interaction as a three layer model in the human stratum corneum using in vivo confocal Raman microscopy Sci. Rep. 2017 7 15900 10.1038/s41598-017-16202-x 29162917 PMC5698327 · DOI
- [29]Tfayli T. Jamal D. Vyumvuhore R. Manfait M. Baillet-Guffro A. Hydration effects on the barrier function of stratum corneum lipids: Raman analysis of ceramides 2, III and 5 Analyst 2013 138 6582 6588 10.1039/c3an00604b 23951566 · DOI
- [30]Liu Y. Lunter D.J. Systematic Investigation of the Effect of Non-Ionic Emulsifiers on Skin by Confocal Raman Spectroscopy—A Comprehensive Lipid Analysis Pharmaceutics 2020 12 223 10.3390/pharmaceutics12030223 PMC7150945 32131544 · DOI
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Sorted by citations
Abdel-Mageed, H. M. (2025) · Inflammopharmacology · doi:10.1007/s10787-025-01642-z · Cited by 45 · see citing works
Artificial intelligence–enabled precision medicine for inflammatory skin diseases
Tang, A. S., Wei, M. L., Haemel, A., La, C., Sirota, M., & Lee, E. Y. (2026) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2025.10.596 · Cited by 6 · see citing works
- Authors
- Dev, K., Ho, C. J. H., Bi, R., Yew, Y. W., S, D. U., Attia, A. B. E., Moothanchery, M., Guan, S. T. T., & Olivo, M.
- Affiliations
- Agency for Science, Technology and Research (SG)
- National Skin Centre (SG)
- National Skin Centre, Singapore 308205, Singapore
- Corresponding author
- Olivo, Malini
- ORCID
- Venue
- Sensors
- Publisher
- MDPI AG
- Published
- 2022-06-21
- Volume
- 22
- Issue
- 13
- Pages
- 4674
- ISSN
- 1424-8220 (ISSN-L)
- PMC
- PMC9269422
- OpenAlex
- W4283387806
- Cited by
- 18
- References
- 1
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 2 · 2023: 4
- FWCI
- 1.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Sensors (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Agency of Science, Technology and Research (A*STAR) (H19H6a0025)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Spectroscopy Techniques in Biomedical and Chemical Research
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Physical Sciences › Chemistry › Analytical Chemistry › Spectroscopy and Chemometric Analyses
- Keywords
- atopic dermatitis, handheld Raman spectroscopy, skin biomarkers, skin barrier dysfunction, PLS-DA, stratum corneum lipids, eczema classification
- MeSH terms
- Machine Learning, Dermatitis, Atopic, Eczema, Humans, Skin, Spectrum Analysis, Raman, Biomarkers
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