title: A database application for pre-processing, storage and comparison of mass spectra derived from patients and controls.
abstract: BACKGROUND
  Statistical comparison of peptide profiles in biomarker discovery requires fast, user-friendly software for high throughput data analysis. Important features are flexibility in changing input variables and statistical analysis of peptides that are differentially expressed between patient and control groups. In addition, integration the mass spectrometry data with the results of other experiments, such as microarray analysis, and information from other databases requires a central storage of the profile matrix, where protein id's can be added to peptide masses of interest.
  
  
  RESULTS
  A new database application is presented, to detect and identify significantly differentially expressed peptides in peptide profiles obtained from body fluids of patient and control groups. The presented modular software is capable of central storage of mass spectra and results in fast analysis. The software architecture consists of 4 pillars, 1) a Graphical User Interface written in Java, 2) a MySQL database, which contains all metadata, such as experiment numbers and sample codes, 3) a FTP (File Transport Protocol) server to store all raw mass spectrometry files and processed data, and 4) the software package R, which is used for modular statistical calculations, such as the Wilcoxon-Mann-Whitney rank sum test. Statistic analysis by the Wilcoxon-Mann-Whitney test in R demonstrates that peptide-profiles of two patient groups 1) breast cancer patients with leptomeningeal metastases and 2) prostate cancer patients in end stage disease can be distinguished from those of control groups.
  
  
  CONCLUSIONS
  The database application is capable to distinguish patient Matrix Assisted Laser Desorption Ionization (MALDI-TOF) peptide profiles from control groups using large size datasets. The modular architecture of the application makes it possible to adapt the application to handle also large sized data from MS/MS- and Fourier Transform Ion Cyclotron Resonance (FT-ICR) mass spectrometry experiments. It is expected that the higher resolution and mass accuracy of the FT-ICR mass spectrometry prevents the clustering of peaks of different peptides and allows the identification of differentially expressed proteins from the peptide profiles.
authors.affiliation: Department of Neurology, Erasmus MC, Rotterdam, The Netherlands. m.titulaer@erasmusmc.nl
authors.forename: Mark K
authors.initials: MK
authors.lastname: Titulaer
authors.forename: Ivar
authors.initials: I
authors.lastname: Siccama
authors.forename: Lennard J
authors.initials: LJ
authors.lastname: Dekker
authors.forename: Angelique L C T
authors.initials: AL
authors.lastname: van Rijswijk
authors.forename: Ron M A
authors.initials: RM
authors.lastname: Heeren
authors.forename: Peter A
authors.initials: PA
authors.lastname: Sillevis Smitt
authors.forename: Theo M
authors.initials: TM
authors.lastname: Luider
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000032:analysis / Q000737:chemistry / Q000145:classification; D003628:Database Management Systems; D030562:Databases, Protein; D003936:Diagnosis, Computer-Assisted / Q000379:methods; D006801:Humans; D016247:Information Storage and Retrieval / Q000379:methods*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000032:analysis* / Q000737:chemistry / Q000145:classification; D009369:Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D010449:Peptide Mapping / Q000379:methods; D012016:Reference Values; D020539:Sequence Analysis, Protein / Q000379:methods; D012984:Software; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins