Biomarker peptide

Figure 7.10 Biomarker detection with an LC-MS chip. (A) Base-peak chromatogram of SCX fraction 7 of the MCF7 protein digest showing the distribution of putative biomarker peptides across the LC-MS run. (Adapted with permission from ref. 33). (B) Mass spectrum that enabled the selection of a PCNA peptide for collision-induced dissociation. Conditions were the same as for Figure 7.9.

Table 11.4 Extract of compiled compound tables from Salmonella enterica subsp. arizonae, S. enterica subsp. houtenae, and S. enterica subsp. enterica prepared for biomarker peptide mass search (raw data from Gekenidis et al. 2014) ...

A number of polypeptide biomarkers have also been identified in the mass range below 4000,28-31 which are cyclic secondary metabolites bonded to lipids or sugars. These peptide sequences are not directly translated from DNA,32... 

Although the feasibility of the proteomics or bioinformatics approach has been demonstrated, considerable room remains for improved methods for selective solublization of protein biomarkers and for rapid cleavage to produce peptides. There is also demand for advanced instrumentation to collect, process, and analyze microorganisms. 

Williams, B. H. Hathout, Y. Fenselau, C. Structural characterization of lipo-peptide biomarkers isolated from Bacillus globigii. J. Mass Spectrom. 2002, 37, 259-264. 

If the scope of mass spectrometry is limitless, why are the applications of clinical MS almost completely small molecules The answer is that most clinical tests analyze small molecules, biomarkers that are either metabolites or steroids and, hence, mass spectrometers would target those first. Perhaps a more complete answer would also include that methods must be very robust, easily reproduced in different labs, reliable, and subjected to an extensive array of validation tests. Although peptide and protein analysis is increasing rapidly in clinical labs, the MS approaches to these assays is lagging behind somewhat. MS techniques targeting these peptides and proteins exist, but they are primarily in the research stage, with few systems and methods subjected to the clinical rigors of validation. Once the necessary validations occur and methods simplified, it will only be a short time before MS is used routinely in clinical proteomics. 

Orioli, M., Aldini, G., Benfatto, M. C., Facini, R. M., and Carini, M. (2007). HNE Michael adducts to histidine and histidine-containing peptides as biomarkers of lipid-derived carbonyl stress in urines LC-MS/MS profiling in Zucker obese rats. Anal. Biochem. 79, 9174-9184. 

Key words Bioinformatics, Biomarker, Clinical proteomics, Proteotypic peptides, Signal transduction,... 

Proteinpedia containing over 4.8 million MS/MS spectra and 2 million peptides, it has already become an important resource for cataloging proteotypic peptides which can be used for biomarker analysis using MRM. 

All four of the proteomic technologies mentioned above (2D-PAGE, HPLC, MS, and protein arrays) are dependent on the use of bioinformatics as a tool for data mining and elucidation. Often, MS runs generate lists of thousands of potential peptide biomarkers, and only with the help of dedicated software tools can the data be analyzed. Computer searches involving databanks of peptides and proteins are used to compare the lists of masses of the proteolytic peptides to theoretical proteolytic products. Matches between the observed mass and the calculated mass can serve as a way of identifying proteins of interest [28-32],... 

A different study purely focused on isolating carrier molecules and their bound proteins to search for biomarkers of clinical interest. It was not only found that circulating carrier proteins were reservoirs for the accumulation and amplification of putative disease markers but also that the low molecular mass proteins that bound to albumin were distinct from those bound to nonalbumin carriers. Using SELDI-TOF, it was further verified that albumin bound peptides associated with ovarian cancer. This demonstrated that albumin capture was an effective method for harvesting disease-relevant biomarkers [66]. 

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