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AmpLyze: A Deep Learning Model for Predicting the Hemolytic Concentration

Created by
  • Haebom

Author

Peng Qiu, Hanqi Feng, Meng-Chun Zhang, Barnabas Poczos

Outline

AmpLyze is a novel model that predicts the erythrocyte hemolysis 50 (HC50) value of antimicrobial peptides (AMPs) solely based on sequence information and accounts for residues that induce hemotoxicity. Unlike existing models that simply classify AMPs as "toxic" or "non-toxic," AmpLyze quantitatively predicts actual HC50 values. It combines residue-level ProtT5/ESM2 embeddings with sequence-level descriptors to construct local and global branches, aligns them through a cross-attention module, and trains them using a log-cosh loss function. The optimized AmpLyze model achieves a PCC of 0.756 and an MSE of 0.987, outperforming existing regression models and state-of-the-art models. Ablation experiments demonstrate that both branches are essential, with cross-attention providing additional performance improvements. Expected-Gradients attribution identifies known toxicity hotspots and suggests safer substitutions. AmpLyze accelerates AMP design by converting hemolysis assessments into quantitative, sequence-based, and interpretable predictions, providing a practical tool for early-stage toxicity screening.

Takeaways, Limitations

Takeaways:
We present AmpLyze, a novel model for quantitatively predicting red blood cell hemolysis (HC50) of antimicrobial peptides.
Achieved higher accuracy (PCC 0.756, MSE 0.987) than existing models.
Provides the ability to identify residues that cause hemolytic toxicity and suggest safer substitutions.
Provides a practical tool useful for AMP design and early toxicity screening.
Limitations:
Further validation of the model's generalization performance is needed.
Performance evaluation of various types of AMPs is required.
Further research is needed on its applicability in actual drug development processes.
Further studies are needed to correlate with in vivo toxicity.
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