title: Unveiling antimicrobial peptide-generating human proteases using PROTEASIX.
abstract: Extracting information from peptidomics data is a major current challenge, as endogenous peptides can result from the activity of multiple enzymes. Proteolytic enzymes can display overlapping or complementary specificity. The activity spectrum of human endogenous peptide-generating proteases is not fully known. Hence, the indirect study of proteolytic enzymes through the analysis of its substrates is largely hampered. Antimicrobial peptides (AMPs) represent a primordial set of immune defense molecules generated by proteolytic cleavage of precursor proteins. These peptides can be modulated by host and microorganismal stimuli, which both dictate proteolytic enzymes' expression and activity. Peptidomics is an attractive approach to identify peptides with a biological role and to assess proteolytic activity. However, bioinformatics tools to deal with peptidomics data are lacking. PROTEASIX is an excellent choice for the prediction of AMPs-generating proteases based on the reconstitution of a substrate's cleavage sites and the crossing of such information with known proteases' specificity retrieved by several publicly available databases. Therefore, the focus of the present tutorial is to explore the potential of PROTEASIX when gather information concerning proteases involved in the generation of human AMPs and to teach the user how to make the most out of peptidomics results using PROTEASIX.
  
  
  
  This tutorial provides a step-by-step guide on to use PROTEASIX for making sense and unveiling the biological implications of peptidomics data. In addition to its educational focus, this work also reveals which proteases contribute the most to the formation of human antimicrobial peptides distributed throughout body fluids in human defense barriers.
authors.affiliation: Institute of Biomedicine - iBiMED, Department of Medical Sciences, University of Aveiro, Portugal; QOPNA, Mass Spectrometry Center, Department of Chemistry, University of Aveiro, Portugal. Electronic address: pauloandrediasbastos@ua.pt.
authors.forename: Paulo
authors.initials: P
authors.lastname: Bastos
authors.affiliation: Institute of Biomedicine - iBiMED, Department of Medical Sciences, University of Aveiro, Portugal; Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Fábio
authors.initials: F
authors.lastname: Trindade
authors.affiliation: QOPNA, Mass Spectrometry Center, Department of Chemistry, University of Aveiro, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Ferreira
authors.affiliation: School of Computer Science, University of Manchester, Kilburn Building, Oxford Road, Manchester, UK.
authors.forename: Mercedes Arguello
authors.initials: MA
authors.lastname: Casteleiro
authors.affiliation: School of Computer Science, University of Manchester, Kilburn Building, Oxford Road, Manchester, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Stevens
authors.affiliation: INSERM U1048, Institute of Cardiovascular and Metabolic Disease, Toulouse, France; Université Toulouse III Paul-Sabatier, Toulouse, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Klein
authors.affiliation: Institute of Biomedicine - iBiMED, Department of Medical Sciences, University of Aveiro, Portugal; Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal. Electronic address: rvitorino@ua.pt.
authors.forename: Rui
authors.initials: R
authors.lastname: Vitorino
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D051188:Knowledge Bases; D010447:Peptide Hydrolases / Q000378:metabolism*; D010455:Peptides / Q000032:analysis; D011498:Protein Precursors / Q000378:metabolism; D020543:Proteome / Q000032:analysis*; D013379:Substrate Specificity
chemical_list: D023181:Antimicrobial Cationic Peptides; D010455:Peptides; D011498:Protein Precursors; D020543:Proteome; D010447:Peptide Hydrolases
keywords: Antimicrobial peptides; Bioinformatics; Knowledgebase; Pathophysiology; Proteases