Extracting biomarkers of commitment to cancer development: potential role of vibrational spectroscopy in systems biology

Theophilou, Georgios; Paraskevaidi, Maria; Lima, Kássio M. G.; Kyrgiou, Maria; Martin‐Hirsch, Pierre L.; Martin, Francis

doi:10.1586/14737159.2015.1028372

Cited by 17 publications

(10 citation statements)

References 230 publications

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“…ATR-FTIR, a well-known method to analyse the chemical structure and interfaces of proteins, lipids, nucleic acid, and carbohydrates biomolecules, proved to be a powerful alternative for spotting spectral variations in pre-malignant and malignant cells [121,122,123], allowing scientists to explore the potential of new biomarkers or spectral fingerprints. Neves et al [124] have used ATR-FTIR for differentiation from blood plasma of NILM (negative for intraepithelial lesion or malignancy) and SIL (squamous intraepithelial lesion) and to divide the cervical squamous intraepithelial lesions into low-grade and high-grade (LSIL and HSIL).…”

Section: Drifting From Molecular To Clinical Practicementioning

confidence: 99%

Vibrational Spectroscopy Fingerprinting in Medicine: from Molecular to Clinical Practice

et al. 2019

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In the last two decades, Fourier Transform Infrared (FTIR) and Raman spectroscopies turn out to be valuable tools, capable of providing fingerprint-type information on the composition and structural conformation of specific molecular species. Vibrational spectroscopy’s multiple features, namely highly sensitive to changes at the molecular level, noninvasive, nondestructive, reagent-free, and waste-free analysis, illustrate the potential in biomedical field. In light of this, the current work features recent data and major trends in spectroscopic analyses going from in vivo measurements up to ex vivo extracted and processed materials. The ability to offer insights into the structural variations underpinning pathogenesis of diseases could provide a platform for disease diagnosis and therapy effectiveness evaluation as a future standard clinical tool.

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Section: Drifting From Molecular To Clinical Practicementioning

confidence: 99%

Vibrational Spectroscopy Fingerprinting in Medicine: from Molecular to Clinical Practice

et al. 2019

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“…Recently, droplet digital PCR (ddPCR) was reported to enable precise DNAm measurements [24,25], and hence it might facilitate epigenetic age predictions without PCR bias. Barcoded bisulfite amplicon sequencing (BBA-seq), which is based on next generation sequencing, enables multiplexed analysis of PCR amplicons [26,27]. The strength of BBA-seq lies within the parallelization of multiple DNA sequences on one lane with relatively long amplicons (up to 500 bases), and with very high coverage (usually > 1000 fold) [28,29].…”

Section: Introductionmentioning

confidence: 99%

New targeted approaches for epigenetic age predictions

et al. 2020

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Background: Age-associated DNA methylation changes provide a promising biomarker for the aging process. While genome-wide DNA methylation profiles enable robust age-predictors by integration of many age-associated CG dinucleotides (CpGs), there are various alternative approaches for targeted measurements at specific CpGs that better support standardized and cost-effective high-throughput analysis. Results: In this study, we utilized 4647 Illumina BeadChip profiles of blood to select CpG sites that facilitate reliable age-predictions based on pyrosequencing. We demonstrate that the precision of DNA methylation measurements can be further increased with droplet digital PCR (ddPCR). In comparison, bisulfite barcoded amplicon sequencing (BBA-seq) gave slightly lower correlation between chronological age and DNA methylation at individual CpGs, while the age-predictions were overall relatively accurate. Furthermore, BBA-seq data revealed that the correlation of methylation levels with age at neighboring CpG sites follows a bell-shaped curve, often associated with a CTCF binding site. We demonstrate that within individual BBA-seq reads the DNA methylation at neighboring CpGs is not coherently modified, but reveals a stochastic pattern. Based on this, we have developed a new approach for epigenetic age predictions based on the binary sequel of methylated and non-methylated sites in individual reads, which reflects heterogeneity in epigenetic aging within a sample. Conclusion: Targeted DNA methylation analysis at few age-associated CpGs by pyrosequencing, BBA-seq, and particularly ddPCR enables high precision of epigenetic age-predictions. Furthermore, we demonstrate that the stochastic evolution of age-associated DNA methylation patterns in BBA-seq data enables epigenetic clocks for individual DNA strands.

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“…Recently, droplet digital PCR (ddPCR) was reported to enable precise DNAm measurements (Yu et al 2015;Zemmour et al 2018), and hence it might facilitate epigenetic age predictions without PCR bias. Barcoded bisulfite amplicon sequencing (BBA-seq), which is based on next generation sequencing, enables multiplexed analysis of PCR amplicons (Bernstein et al 2015;Theophilou et al 2015). The strength of BBA-seq lies within the parallelization of multiple DNA sequences on one lane with relatively long amplicons (up to 500 bases), and with very high coverage (usually > 1000 fold) (Smith et al 2010;Franzen et al 2017).…”

Section: Introductionmentioning

confidence: 99%

New Targeted Approaches for Epigenetic Age Predictions

Han

Franzen

Stiehl

et al. 2019

Preprint

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Aging causes epigenetic modifications, which are utilized as a biomarker for the aging process.While genome-wide DNA methylation profiles enable robust age-predictors by integration of many age-associated CG dinucleotides (CpGs), there are various alternative approaches for targeted measurements at specific CpGs that better support standardized and cost-effective highthroughput analysis. In this study, we utilized 4,650 Illumina BeadChip datasets of blood to select the best suited CpG sites for targeted analysis. DNA methylation analysis at these sites with either pyrosequencing or droplet digital PCR (ddPCR) revealed a high correlation with chronological age.In comparison, bisulfite barcoded amplicon sequencing (BBA-seq) gave slightly lower precision at individual CpGs. However, BBA-seq data revealed that the correlation of methylation levels with age at neighboring CpG sites follows a bell-shaped curve, often accompanied by a CTCF binding site at the peak. We demonstrate that within individual BBA-seq reads the DNA methylation at neighboring CpGs is not coherently modified but reveals a stochastic pattern. Based on this, we have developed an alternative model for epigenetic age predictions based on the binary sequel of methylated and non-methylated sites in individual reads, which reflects heterogeneity in epigenetic aging within a sample. Thus, the stochastic evolution of age-associated DNA methylation patterns, which seems to resemble epigenetic drift, enables epigenetic clocks for individual DNA strands.

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Extracting biomarkers of commitment to cancer development: potential role of vibrational spectroscopy in systems biology

Cited by 17 publications

References 230 publications

Vibrational Spectroscopy Fingerprinting in Medicine: from Molecular to Clinical Practice

Vibrational Spectroscopy Fingerprinting in Medicine: from Molecular to Clinical Practice

New targeted approaches for epigenetic age predictions

New Targeted Approaches for Epigenetic Age Predictions

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