Extensive MALDI-TOF/TOF and LTQ Orbitrap MS/MS analyses coupled with database searches [29, 30] were performed to sequence and identify these peptide biomarkers. The identity of a subset of peptides detected was determined by searching MS/MS spectra against the Swiss-Prot database (June 10, 2008) restricted to human entries (15,720 sequences) using the Mascot (version 1.9.05) search engine. Searches were restricted to 50 and 100 ppm for parent and fragment ions, respectively. No enzyme restriction was selected. Since we were focusing on the naturally occurring peptides, hits were considered significant when they were above the statistical significant threshold (as returned by Mascot). Selected MS/MS spectra were also searched by SEQUEST (BioWorks™ rev.3.3.1 SP1) against the International Protein Index human database version 3.5.7 restricted to human entries (76,541 sequences). mMASS, an open source mass spectrometry tool (http://mmass.biographics.cz/), was used for manual review of the protein identification and MS/MS ion pattern analysis for additional validation.