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A novel bioinformatics’ platform to identify key proteasic pathways involved in kidney diseases

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Unravelling disease pathways

EU support has enabled scientists to develop an important tool linking peptide biomarkers of diseases with the enzymes that generate them. Getting even one step closer to the mechanisms of diseases will point to new biomarkers and potential routes to therapies.

Health

Peptides are small pieces of proteins. Recent research has identified numerous peptides that are biomarkers of diseases affecting kidney, cardiovascular and autoimmune systems or related to infectious diseases or cancer. Many of these are readily accessible in bodily fluids such as cerebrospinal fluid, serum and urine. The innovative EU-funded study 'A novel bioinformatics' platform to identify key proteasic pathways involved in kidney diseases' (PROTEASIX) sought to link the peptides to their proteases based on cleavage sites. Knowledge of the proteases involved in the diseases will provide additional potential targets for therapies. There are currently a number of databases linking proteases and their cleavage sites. However, the information is scattered, the formats varied and the search methods inefficient. The open-source PROTEASIX tool can be used in an automatic and large-scale search that predicts proteases potentially involved in generation of a given peptide sequence. The human genome encodes more than 500 proteases. The PROTEASIX database contains 3 500 entries regarding human protease and cleavage site combinations. Scientists tested the function of the tool by comparing analysis of 1 388 peptides found in human urine samples against 1 003 randomly generated cleavage sites. The tool returned almost no results for the random sites but identified metalloprotease activity as predominantly involved in generation of urinary peptides. While experiments are required to confirm the in silico predictions, the tool provides a powerful way to get at the possible mechanisms of many disease processes via associated peptide biomarkers. PROTEASIX will make a major contribution to understanding of the role of protease networks in health and pathology. Exploitation is expected to point to new biomarkers and drug development for cardiovascular, inflammatory, and fibrotic or neurological disorders as well as many types of cancer.

Keywords

Disease pathways, peptide, peptide biomarkers, diseases, enzymes, bioinformatics' platform, proteasic pathways, kidney diseases, proteases, cleavage sites, human genome, metalloprotease activity, urinary peptides, protease networks

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