Proteasix: a tool for automated and large-scale prediction of proteases involved in naturally occurring peptide generation.
In this study, we have developed Proteasix, an open-source peptide-centric tool that can be used to predict in silico the proteases involved in naturally occurring peptide generation. We developed a curated cleavage site (CS) database, containing 3500 entries about human protease/CS combinations. On top of this database, we built a tool, Proteasix, which allows CS retrieval and protease associations from a list of peptides. To establish the proof of concept of the approach, we used a list of 1388 peptides identified from human urine samples, and compared the prediction to the analysis of 1003 randomly generated amino acid sequences. Metalloprotease activity was predominantly involved in urinary peptide generation, and more particularly to peptides associated with extracellular matrix remodelling, compared to proteins from other origins. In comparison, random sequences returned almost no results, highlighting the specificity of the prediction. This study provides a tool that can facilitate linking of identified protein fragments to predicted protease activity, and therefore into presumed mechanisms of disease. Experiments are needed to confirm the in silico hypotheses; nevertheless, this approach may be of great help to better understand molecular mechanisms of disease, and define new biomarkers, and therapeutic targets.
School of Computer Science, University of Manchester, Kilburn Building, Oxford Road, Manchester, UK. julie.klein64@gmail.com
Julie
J
Klein
James
J
Eales
Petra
P
Zürbig
Antonia
A
Vlahou
Harald
H
Mischak
Robert
R
Stevens
D000595:Amino Acid Sequence; D001331:Automation; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism* / Q000652:urine; D012984:Software; D013379:Substrate Specificity
D010455:Peptides; D010447:Peptide Hydrolases; D020782:Matrix Metalloproteinases