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Enhancing anticancer peptide discovery: A Fusion-Centric Framework With Conditional Diffusion For Prediction And Generation
Xinjiang University, Urumqi, China; University of Electronic Science and Technology of China, Quzhou, China.
University of Electronic Science and Technology of China, Quzhou, China; Chinese Academy of Sciences, Hangzhou, China.
Xinjiang University, Urumqi, China.
Halmstad University, School of Information Technology.ORCID iD: 0000-0002-2851-4260
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2026 (English)In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 22, no 3, p. 1-29, article id e1014098Article in journal (Refereed) Published
Abstract [en]

Anticancer peptides (ACPs) are short bioactive sequences that selectively target tumor cells with minimal toxicity, positioning them as promising candidates for next-generation cancer therapies. However, existing computational models face limitations in sequence representation and class imbalance. To address these challenges, we propose UACD-ACPs, a unified fusion-driven framework that integrates a diffusion-inspired noise-conditioned classifier for ACP prediction and a diffusion-based peptide generation module with cancer-type-aware organization for targeted downstream screening. The classification module integrates ProtBERT-based semantic embeddings with physicochemical descriptors via the Multiscale Embedding Compression Strategy (MECS) and a diffusion-inspired noise-conditioned encoder, substantially enhancing predictive robustness and accuracy, particularly under challenging imbalanced multi-class settings. In the generative pipeline, we introduce a denoising diffusion-based generative framework augmented by two novel fusion modules: the Bitemporal Fusion Module (BFM) and the Temporal Feature Attention Module (TFAM). These modules perform multi-scale temporal and semantic fusion to promote the generation of structurally coherent and functionally relevant peptide candidates. Experimental results demonstrate that UACD-ACPs outperforms state-of-the-art methods in terms of accuracy, F1-score, and AUC-ROC. The generated peptides exhibit favorable physicochemical properties, diverse secondary structures, and strong structural stability, as validated by molecular dynamics simulations and membrane-binding analyses. Overall, this study highlights the potential of fusion-driven diffusion-based frameworks for alleviating class imbalance and data heterogeneity in anticancer peptide modeling, paving the way for scalable and biologically grounded ACP discovery. © 2026 Li et al.

Place, publisher, year, edition, pages
San Francisco: Public Library of Science (PLoS), 2026. Vol. 22, no 3, p. 1-29, article id e1014098
Keywords [en]
identification, inhibitor, language
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Bioinformatics (Computational Biology) Bioinformatics (Computational Biology)
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URN: urn:nbn:se:hh:diva-58706DOI: 10.1371/journal.pcbi.1014098ISI: 001724448300001PubMedID: 41886705Scopus ID: 2-s2.0-105034373461OAI: oai:DiVA.org:hh-58706DiVA, id: diva2:2050913
Available from: 2026-04-07 Created: 2026-04-07 Last updated: 2026-04-27Bibliographically approved

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Tiwari, Prayag

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