title: Inferring serum proteolytic activity from LC-MS/MS data.
abstract: BACKGROUND
  In this paper we deal with modeling serum proteolysis process from tandem mass spectrometry data. The parameters of peptide degradation process inferred from LC-MS/MS data correspond directly to the activity of specific enzymes present in the serum samples of patients and healthy donors. Our approach integrate the existing knowledge about peptidases' activity stored in MEROPS database with the efficient procedure for estimation the model parameters.
  
  
  RESULTS
  Taking into account the inherent stochasticity of the process, the proteolytic activity is modeled with the use of Chemical Master Equation (CME). Assuming the stationarity of the Markov process we calculate the expected values of digested peptides in the model. The parameters are fitted to minimize the discrepancy between those expected values and the peptide activities observed in the MS data. Constrained optimization problem is solved by Levenberg-Marquadt algorithm.
  
  
  CONCLUSIONS
  Our results demonstrates the feasibility and potential of high-level analysis for LC-MS proteomic data. The estimated enzyme activities give insights into the molecular pathology of colorectal cancer. Moreover the developed framework is general and can be applied to study proteolytic activity in different systems.
authors.affiliation: Institute of Informatics, University of Warsaw, Banacha 2, 02-097 Warsaw, Poland. piotr.dittwald@mimuw.edu.pl
authors.forename: Piotr
authors.initials: P
authors.lastname: Dittwald
authors.forename: Jerzy
authors.initials: J
authors.lastname: Ostrowski
authors.forename: Jakub
authors.initials: J
authors.lastname: Karczmarski
authors.forename: Anna
authors.initials: A
authors.lastname: Gambin
mesh_terms: D000465:Algorithms; D002853:Chromatography, Liquid / Q000379:methods; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000201:enzymology; D006801:Humans; D008390:Markov Chains; D013058:Mass Spectrometry / Q000379:methods; D015233:Models, Statistical; D010447:Peptide Hydrolases / Q000032:analysis*; D059748:Proteolysis; D044967:Serum / Q000737:chemistry*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D010447:Peptide Hydrolases