PredLyP: A computational tool for predicting tissue-specific (phago-)lysosomal post-digestion peptides
Computational and Structural Biotechnology Journal, vol. 27, pp. 4645–4656
Abstract
Peptides are versatile tools in immunotherapy, serving as vaccines and targets for specific immunotherapeutic strategies. Peptides engage immune cells like macrophages and T cells, enabling precise modulation of immune responses. In this context, we highlight the utility of macrophages, innate immune cells involved in constant surveillance, for detecting their phagolysosomal content as a minimally-invasive biomarker strategy. Analyzing proteolytic patterns in phagolysosomes offers a high-sensitivity approach to assess tissue homeostasis and tissue disruption, such as in cancer. Despite their potential, a major challenge lies in the lack of comprehensive tools for predicting cutting sites across phagolysosomal proteases. Therefore, we developed the computational tool PredLyP (abbreviation for "prediction of lysosomal proteases") to identify cutting sites of phagolysosomal proteases, which are essential enzymes involved in protein degradation within (phago)lysosomes, to predict the potential peptides generated from the input proteins. Unlike existing tools, PredLyP utilizes Position Specific Scoring Matrices derived from amino acid sequences, physical (charge and hydropathy) and structural (secondary structure and solvent accessibility) features. Moreover, it incorporates a sequential cutter functionality that mimics the ordered action of proteases, providing predictive insights into substrate fragment generation. Comparisons with other tools demonstrate the superior sensitivity of PredLyP, enabling accurate prediction of complete and partial digestion fragments, a critical requirement for real-world applications in proteomics, antibody development, and immune system research. Overall, PredLyP represents a robust tool for advancing our understanding of proteolytic processes in phagolysosomes and their implications in health and disease.
Authors 7
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Leiden University Medical Center
Affiliation as printed
Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands
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Consejo Superior de Investigaciones Científicas · Universidad de Salamanca · Leiden University Medical Center · Instituto de Salud Carlos III · Instituto de Investigación Biomédica de Salamanca · Centro de Investigación del Cáncer · Centro de Investigación Biomédica en Red de Cáncer
Affiliation as printed
Biomedical Research Networking Centre Consortium of Oncology (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
Cytometry Service, NUCLEUS, Madrid, Spain
Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands
Department of Medicine, University of Salamanca (Universidad de Salamanca), Salamanca, Spain
Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain
Translational and Clinical Research Program, Cancer Research Center (IBMCC, CSIC – University of Salamanca), Instituto de Salud Carlos III, Madrid, Spain
Translational and Clinical Research Program, Cancer Research Center (IBMCC, CSIC - University of Salamanca), Instituto de Salud Carlos III, Madrid, Spain
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Leiden University Medical Center
Affiliation as printed
Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands
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Jacques J. M. van Dongen corresponding Aachen Department of Immunology, Leiden University Medical Center
Consejo Superior de Investigaciones Científicas · Universidad de Salamanca · Leiden University Medical Center · Instituto de Salud Carlos III · Instituto de Investigación Biomédica de Salamanca · Centro de Investigación del Cáncer · Centro de Investigación Biomédica en Red de Cáncer
Affiliation as printed
Biomedical Research Networking Centre Consortium of Oncology (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
Cytometry Service, NUCLEUS, Madrid, Spain
Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands
Department of Medicine, University of Salamanca (Universidad de Salamanca), Salamanca, Spain
Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain
Translational and Clinical Research Program, Cancer Research Center (IBMCC, CSIC – University of Salamanca), Instituto de Salud Carlos III, Madrid, Spain
Translational and Clinical Research Program, Cancer Research Center (IBMCC, CSIC - University of Salamanca), Instituto de Salud Carlos III, Madrid, Spain
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Leiden University Medical Center · Delft University of Technology
Affiliation as printed
Delft Bioinformatics Lab, Delft Technical University, Delft, the Netherlands
Leiden Computational Biology Center, Leiden University Medical Center, Leiden, the Netherlands
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Consejo Superior de Investigaciones Científicas · Universidad de Oviedo · Universidad de Salamanca · Leiden University Medical Center · Instituto de Salud Carlos III · Instituto de Investigación Biomédica de Salamanca · Centro de Investigación del Cáncer · Centro de Investigación Biomédica en Red de Cáncer
Affiliation as printed
Biomedical Research Networking Centre Consortium of Oncology (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
Cytometry Service, NUCLEUS, Madrid, Spain
Department of Functional Biology (Immunology area), Faculty of Medicine and Health Sciences, University of Oviedo, Oviedo, Spain
Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands
Department of Medicine, University of Salamanca (Universidad de Salamanca), Salamanca, Spain
Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain
Translational and Clinical Research Program, Cancer Research Center (IBMCC, CSIC – University of Salamanca), Instituto de Salud Carlos III, Madrid, Spain
Translational and Clinical Research Program, Cancer Research Center (IBMCC, CSIC - University of Salamanca), Instituto de Salud Carlos III, Madrid, Spain
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Indu Khatri corresponding Aachen Department of Immunology, Leiden University Medical Center Leiden Computational Biology Center
Leiden University Medical Center
Affiliation as printed
Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands
Leiden Computational Biology Center, Leiden University Medical Center, Leiden, the Netherlands
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