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Auteurs principaux: Zhao, Yingqi, Zhan, Kuo, Xin, Pei-Lin, Liang, Yuge, Agyekum, Enock Adjei, Putkonen, Matti, Li, Shuai, De Angelis, Francesco, Huang, Jianan
Format: Preprint
Publié: 2026
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Accès en ligne:https://arxiv.org/abs/2605.21084
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author Zhao, Yingqi
Zhan, Kuo
Xin, Pei-Lin
Liang, Yuge
Agyekum, Enock Adjei
Putkonen, Matti
Li, Shuai
De Angelis, Francesco
Huang, Jianan
author_facet Zhao, Yingqi
Zhan, Kuo
Xin, Pei-Lin
Liang, Yuge
Agyekum, Enock Adjei
Putkonen, Matti
Li, Shuai
De Angelis, Francesco
Huang, Jianan
contents Post-translational modifications (PTMs) play essential roles in regulating protein structure, function, and cellular signalling. However, peptide level discrimination of hydroxylation at the single-molecule level remains difficult. Here, we report a particle-in-pore single-molecule surface-enhanced Raman spectroscopy (SERS) platform combined with peak occurrence frequency (POF) analysis and a one-dimensional convolutional neural network (1D-CNN) for discriminating hydroxylated and non-hydroxylated HIF peptide fragments. Three peptide pairs containing the Pro-564 hydroxylation site, with lengths of 7, 9, and 15 amino acids (AAs), were investigated. POF analysis revealed reproducible hydroxylation-dependent spectral changes in the 7AA and 9AA peptide pairs, which were attributed to changes in adsorption conformation and surface interactions. CNN-based classification achieved post-evaluation accuracies of 72.98%, 78.55%, and 89.74% for the 7AA, 9AA, and 15AA peptide pairs, respectively, with AUC values above 0.80 for all the pairs, indicating a reliable discrimination. Gradient-weighted feature visualization further showed that CNN-sensitive regions overlapped with recurrent POF features, supporting the chemical relevance of the learned classification patterns. Notably, for the 15AA peptide pair, the enhanced citrate-associated band suggests that hydroxylation can substantially alter peptide-gold nanoparticle adsorption behaviour. This adsorption-mediated effect may amplify hydroxylation-induced spectral differences and contribute to the improved discrimination accuracy despite the increased structural complexity. These results demonstrate that the particle-in-pore sensor, assisted by deep learning, can capture hydroxylation-induced spectral and adsorption changes in peptide fragments, providing a promising strategy for ultrasensitive analysis of weak PTM signatures in peptides.
format Preprint
id arxiv_https___arxiv_org_abs_2605_21084
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle Label-free SERS Discrimination of Native Proline Hydroxylation at Single-molecule peptide by Deep Learning-assisted plasmonic nanopore
Zhao, Yingqi
Zhan, Kuo
Xin, Pei-Lin
Liang, Yuge
Agyekum, Enock Adjei
Putkonen, Matti
Li, Shuai
De Angelis, Francesco
Huang, Jianan
Biological Physics
Post-translational modifications (PTMs) play essential roles in regulating protein structure, function, and cellular signalling. However, peptide level discrimination of hydroxylation at the single-molecule level remains difficult. Here, we report a particle-in-pore single-molecule surface-enhanced Raman spectroscopy (SERS) platform combined with peak occurrence frequency (POF) analysis and a one-dimensional convolutional neural network (1D-CNN) for discriminating hydroxylated and non-hydroxylated HIF peptide fragments. Three peptide pairs containing the Pro-564 hydroxylation site, with lengths of 7, 9, and 15 amino acids (AAs), were investigated. POF analysis revealed reproducible hydroxylation-dependent spectral changes in the 7AA and 9AA peptide pairs, which were attributed to changes in adsorption conformation and surface interactions. CNN-based classification achieved post-evaluation accuracies of 72.98%, 78.55%, and 89.74% for the 7AA, 9AA, and 15AA peptide pairs, respectively, with AUC values above 0.80 for all the pairs, indicating a reliable discrimination. Gradient-weighted feature visualization further showed that CNN-sensitive regions overlapped with recurrent POF features, supporting the chemical relevance of the learned classification patterns. Notably, for the 15AA peptide pair, the enhanced citrate-associated band suggests that hydroxylation can substantially alter peptide-gold nanoparticle adsorption behaviour. This adsorption-mediated effect may amplify hydroxylation-induced spectral differences and contribute to the improved discrimination accuracy despite the increased structural complexity. These results demonstrate that the particle-in-pore sensor, assisted by deep learning, can capture hydroxylation-induced spectral and adsorption changes in peptide fragments, providing a promising strategy for ultrasensitive analysis of weak PTM signatures in peptides.
title Label-free SERS Discrimination of Native Proline Hydroxylation at Single-molecule peptide by Deep Learning-assisted plasmonic nanopore
topic Biological Physics
url https://arxiv.org/abs/2605.21084