As it was therefore necessary to reduce the level of abundant proteins, in this follow up study, particular relevance was given to the content of the contaminant protein hemoglobin. Only non-hemolytic samples with similar, low contents of hemoglobin were included in the study. Additionally, to further increase the likelihood to identify statistically significant discriminatory biomarkers, we introduced a fractioning step based on anion-exchange chromatography. In a similar study performed with MALDI-TOF [28] , where serum samples were analyzed in the first weeks (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14) (15) (16) Table 3 ). Furthermore, two peaks identified in this study (23. 162 and 14.843 kDa) were similar to peaks identified elsewhere (corresponding to Heat shock 27 kDa protein 1 [29] [30] [31] and Galectin 1 [26, 31] , respectively). In accordance with [31] , the identified peak corresponding to Heat shock 27 kDa protein 1 was upregulated, while the peak corresponding to Galectin 1 was down-regulated. Thus, these proteins seem to be very interesting and suitable candidates for future investigations. The preponderance of the significant biomarkers had a molecular mass lower than 20 kDa, confirming that small peptides are a rich source of relevant biomarkers in SELDI-TOF MS analyses as previously reported in human [36] and ovine [19] sera. This may also partly be caused by the fact that the low molecular weight region (LMW) of the serum proteome, called peptidome, is an assortment of small intact proteins and proteolytic fragments of larger proteins, including several classes of physiologically important proteins like peptide hormones and components of both the innate and adaptive immune systems (i.e. cytokines and chemokines) [35, 37] . This is particularly interesting as the patho-physiological state of the body's tissue is predominantly reflected in the LMW and low abundance region of the serum proteome, and specific protein fragments of the serum peptidome have been shown to contain a rich source of disease-specific diagnostic information and they have been correlated with disease stages in several studies (reviewed by [37] ).