Biomarker discovery group

In order to design a successful biomarker discovery project it is necessary to put together the right people and a solid experimental plan. A brief description of the biomarker discovery group and experiment are outlined in this section. 

The anatomy of a successful biomarker discovery group generally contains the following skill sets ... 

Surface enhanced laser desorption/ionization (SELDI) is a distinctive form of laser desorption ionization where the target plays an active role in the sample preparation procedure and ionization process [49]. Depending on the chemical or biochemical treatment, the SELDI surface acts as solid phase extraction or an affinity probe. Chromatographic surface is used for sample fractionation and purification of biological samples prior to direct analysis by laser desorption/ ionization. SELDI is mainly applied for protein profiling and in biomarker discovery by comparing protein profiles from control and patient groups. 

New biomarker discovery from such studies can lead to early detection of deleterious effects. In a more recent study, researchers validated toxicological protein markers from an in vivo system (rat liver) as well as from an in vitro system (human HepG2 cell line) [86]. They reported a total of 11 protein markers with reactivity toward multiple toxic compounds and no reactivity toward nontoxic compounds. An important conclusion from this work is that cells in culture can be used as an in vitro toxicity testing system to assess hepatotoxicity. However, in the future, a much more extensive study may be required to identify a larger group of toxicology markers to detect more diverse types of toxic reactions. 

While the above study utilized urine, probably no biofluid has attracted the attention of the proteomic biomarker discovery field as serum and plasma. Although the analysis of serum by RPLC-MS has almost become routine, such is not the case for CE-MS. In a proof of principle study to show the efficacy of using CE-MS to find differentially abundant proteins in serum, the group of Sassi et al. analyzed groups of sera that were spiked with different concentrations of known standard peptides. The groups of sera were analyzed by CE-MS and the standard peptides were successfully identified as being differentially abundant with a success rate of 95%. 

To this end it is important to take a multidisciplinary approach to biomarker discovery. There are a number of difficult tasks to be accomplished in the process of biomarker discovery, each requiring expertise in different fields, separation technology, medicine, pathology of the disease, the chemistry of the type of molecule that is the target of the study, and statistical analysis. The conclusion from these facts is that a multidisciplinary approach to biomarker discovery is necessary. Once the group is assembled, it is then vital that members of the group listen to each other about the capabilities and weaknesses in each area of a project before starting the actual work. 

When putting together a group for biomarker discovery it is important to understand what type of expertise will be required to accomplish the goals of the project. This is... 

After xenobiotic/toxin exposure, differentially expressed proteins are identified by the comparison of SELDI spectra from control and treated samples. By combining groupwise statistics with N-fold regulations, single biomarkers (m/z) can be selected. As to be expected from the complexity of the proteome, in many cases no single marker will be able to discriminate between the groups. Rather, a complex pattern of multiple markers will be acquired (Figure 8). Discovery of such markers/pattems can be successful by application of multivariate statistics methods on the data set. However, for the identification of specific protein expression patterns bioinformatics tools are... 

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