Serum protein profiling in mice: Identification of Factor XIIIa as a potential biomarker for muscular dystrophy

Abstract

Protein profiling in blood serum by fractionation and MS analysis has been applied in mice to assess its applicability as a fast, economical alternative to current DNA and RNA analyses for diagnosis of neuromuscular disorders. Mass spectra of peptides and proteins were generated using serum from dystrophin-deficient mdx and control mice by WCX ClinProt bead fractionation, followed by MALDI-MS. Double cross-validatory linear discriminant and logistic regression data analysis methods were compared with a new Bayesian logistic regression method. These were evaluated on their ability to discriminate between healthy and dystrophic samples, and to identify the discriminatory peaks in the mass spectra. All three approaches classified the spectra with comparable misclassification rates (between 18.4 and 20.6%), with much overlap between the differential peaks identified between the methods. The differential peak pattern from the Bayesian method was sparser and easier to interpret than from the other two methods, without compromising classifying strength. One of the two main differentiating peaks at m/z 3908 was identified as an N-terminal peptide of coagulation Factor XIIIa, previously identified in human serum. This work underlines the translational aspect of serum protein profiling in mice and supports a further study with serum from patients with neuromuscular disorders.

Diversity of human skeletal muscle in health and disease: Contribution of proteomics

“…By increasing the number of investigated subjects, the number of significant changes may possibly decrease, being likely more than compensated by an increased robustness of the results. Animal models could provide further hints for the detection of new biomarkers of muscle damage in sera, particularly when based on an extensive proteome analysis of muscles differently affected by the disease as is the case for the mdx animal model [101,102].…”

Serum peptidome patterns of hepatocellular carcinoma based on magnetic bead separation and mass spectrometry analysis

“…Interestingly, low-molecular-weight peptides, such as S100A8 and fibrinogen, have been recognized to play important roles in physiologic and pathologic processes and could be used as relevant biomarker candidates (23,24). Recently, the mass spectrum that directly detects and differentiates short peptides has offered a promising approach for peptidomic biomarker discovery (8,12,(25)(26)(27).…”

Comparative Serum Proteomic Analysis of Serum Diagnosis Proteins of Colorectal Cancer Based on Magnetic Bead Separation and MALDI-TOF Mass Spectrometry

“…It is being interestingly recognized that low mass weight peptides, such as S100A8 and fibrinogen, play an important role in physiological and pathological process and could be used as relevant biomarker candidates (Cheng et al, 2005;Tolson et al, 2006). Recently mass spectrum that directly detects and differentiates short peptides has offered a promising approach for peptidomic biomarker discovery (Alagaratnam et al, 2008;Chinello et al, 2010;Dai et al, 2010;Du et al, 2010;Liu et al, 2010).…”