DREAM-B3P: Dual-Stream Transformer Network Enhanced by Feedback Diffusion Model for Blood-Brain Barrier Penetrating Peptide Prediction

Fuente: arXiv
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Main Authors: Wang, Kaijie, Yin, Le, Tian, Aodi, Wei, Zhiqiang, Yang, Zai, Han, Min, Wei, Qichun, Wang, Sheng
Format: Preprint
Published: 2025
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author Wang, Kaijie
Yin, Le
Tian, Aodi
Wei, Zhiqiang
Yang, Zai
Han, Min
Wei, Qichun
Wang, Sheng
author_facet Wang, Kaijie
Yin, Le
Tian, Aodi
Wei, Zhiqiang
Yang, Zai
Han, Min
Wei, Qichun
Wang, Sheng
contents Introduction: The blood-brain barrier (BBB) protects the central nervous system but prevents most neurotherapeutics from reaching effective concentrations in the brain. BBB-penetrating peptides (BBBPs) offer a promising strategy for brain drug delivery; however, the scarcity of positive samples and severe class imbalance hinder the reliable identification of BBBPs. Objectives: Our goal is to alleviate class imbalance in BBBP prediction and to develop an accurate, interpretable classifier for BBBP prediction. Methods: We propose DREAM-B3P, which couples a feedback diffusion model (FB-Diffusion) for data augmentation with a dual-stream Transformer for classification. FB-Diffusion learns the BBBP distribution via iterative denoising and uses an external analyzer to provide feedback, generating high-quality pseudo-BBBPs. The classifier contains a sequence stream that extracts structural features from peptide sequences and a physicochemical stream that captures physicochemical features such as hydrophobic surface area, molecular charge, number of rotatable bonds, and polarizability. Combining the two features leads to superior BBBP predictive performance. Results: On a benchmark test set containing equal numbers of BBBPs and non-BBBPs, DREAM-B3P surpasses baseline methods (Deep-B3P, B3Pred, BBPpredict and Augur), improving AUC/ACC/MCC by 4.3\%/17.8\%/14.9\%, respectively, over the second-best method. Conclusion: By integrating feedback diffusion with a dual-stream Transformer classifier, DREAM-B3P effectively mitigates data scarcity and imbalance and achieves state-of-the-art performance.
format Preprint
id arxiv_https___arxiv_org_abs_2512_11511
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle DREAM-B3P: Dual-Stream Transformer Network Enhanced by Feedback Diffusion Model for Blood-Brain Barrier Penetrating Peptide Prediction
Wang, Kaijie
Yin, Le
Tian, Aodi
Wei, Zhiqiang
Yang, Zai
Han, Min
Wei, Qichun
Wang, Sheng
Quantitative Methods
Introduction: The blood-brain barrier (BBB) protects the central nervous system but prevents most neurotherapeutics from reaching effective concentrations in the brain. BBB-penetrating peptides (BBBPs) offer a promising strategy for brain drug delivery; however, the scarcity of positive samples and severe class imbalance hinder the reliable identification of BBBPs. Objectives: Our goal is to alleviate class imbalance in BBBP prediction and to develop an accurate, interpretable classifier for BBBP prediction. Methods: We propose DREAM-B3P, which couples a feedback diffusion model (FB-Diffusion) for data augmentation with a dual-stream Transformer for classification. FB-Diffusion learns the BBBP distribution via iterative denoising and uses an external analyzer to provide feedback, generating high-quality pseudo-BBBPs. The classifier contains a sequence stream that extracts structural features from peptide sequences and a physicochemical stream that captures physicochemical features such as hydrophobic surface area, molecular charge, number of rotatable bonds, and polarizability. Combining the two features leads to superior BBBP predictive performance. Results: On a benchmark test set containing equal numbers of BBBPs and non-BBBPs, DREAM-B3P surpasses baseline methods (Deep-B3P, B3Pred, BBPpredict and Augur), improving AUC/ACC/MCC by 4.3\%/17.8\%/14.9\%, respectively, over the second-best method. Conclusion: By integrating feedback diffusion with a dual-stream Transformer classifier, DREAM-B3P effectively mitigates data scarcity and imbalance and achieves state-of-the-art performance.
title DREAM-B3P: Dual-Stream Transformer Network Enhanced by Feedback Diffusion Model for Blood-Brain Barrier Penetrating Peptide Prediction
topic Quantitative Methods
url https://arxiv.org/abs/2512.11511