DeepCleave

DeepCleave predicts protease-specific substrates and their cleavage sites from protein substrate sequences using convolutional neural networks and transfer learning to characterize cleavage patterns for caspases and matrix metalloproteases.


Key Features:

  • High-Quality Cleavage Site Features: Cleavage-site-specific features are extracted from substrate sequences via deep learning to represent sequence signals around cleavage positions.
  • Convolutional Neural Networks (CNNs): CNNs model local sequence patterns and contextual information around putative cleavage sites.
  • Transfer Learning: Transfer learning is applied to leverage pre-existing knowledge and improve model generalization across datasets.
  • Multiple Kernels and Attention Layer: Multiple convolutional kernels and an attention layer are integrated into the network architecture for nuanced sequence analysis.
  • Performance Benchmarking: Empirical evaluations report superior predictive performance relative to several state-of-the-art methods for caspase and matrix metalloprotease cleavage-site prediction.

Scientific Applications:

  • Protease Substrate Identification: Identification of potential substrates and precise cleavage sites for caspases and matrix metalloproteases.
  • Proteolytic Pathway Analysis: Analysis of proteolytic pathways and protease-specific cleavage patterns in protein life-cycle regulation.
  • Disease-related Proteolysis Studies: Investigation of proteolytic impacts and physiological consequences of caspase and matrix metalloprotease activity in health and disease.

Methodology:

DeepCleave uses protein substrate sequence data as input, employs convolutional neural networks with multiple kernels and an attention layer, applies transfer learning, and extracts cleavage-site features through deep learning-based feature representation.

Topics

Details

Tool Type:
web application
Added:
11/14/2019
Last Updated:
11/24/2024

Operations

Publications

Li F, Chen J, Leier A, Marquez-Lago T, Liu Q, Wang Y, Revote J, Smith AI, Akutsu T, Webb GI, Kurgan L, Song J. DeepCleave: a deep learning predictor for caspase and matrix metalloprotease substrates and cleavage sites. Bioinformatics. 2019;36(4):1057-1065. doi:10.1093/bioinformatics/btz721. PMID:31566664. PMCID:PMC8215920.

PMID: 31566664
PMCID: PMC8215920
Funding: - Australian Research Council: DP120104460, LP110200333 - National Health and Medical Research Council of Australia: 1092262, 490989 - National Institute of Allergy and Infectious Diseases of the National Institutes of Health: R01 AI111965 - Collaborative Research Program of Institute for Chemical Research, Kyoto University: 2019-32