Tools for Biomarker Discovery

The only point that we hope to make in this chapter about mass spectrometry instrumentation is that this technology is rapidly becoming the method of choice for the detection, characterization, and identification of biomolecules. 

From the available mass spectrometry instrument configurafions, there are one or more instruments available to look at the type of molecule that you are interested in. The tools for biomarker discovery can seem complicated and diverse, but they accomplish one of these three things separation, detection, and identification. 

The discovery of biomarkers will require each of these three steps to be done in order to discover a biomarker from a biological sample. Biological samples are highly complex mixtures of molecules many of which will interfere with each other, and thus sample preparation methods are required to first isolate the class of molecule that one is interested in. The samples that have been optimized for a particular class of biomolecule (optimized samples) can then be more efficiently 

We will not discuss in detail each of these technologies in this section. The lists provided are not complete since very specific separation, detection, and identification tools exist we will attempt to briefly mention the most general and ofien-used tools. 

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Reyzer, M. L., and Caprioli, R. M. (2005b). MALDI mass spectrometry for direct tissue analysis A new tool for biomarker discovery. J. Proteome Res. 4 1138-1142. 

DEVELOPMENTS ENABLING MASS SPECTROMETRY AS A TOOL FOR BIOMARKER DISCOVERY... 

S.L. Robinette, J.C. Lindon, J.K. Nicholson, Statistical spectroscopic tools for biomarker discovery and systems medicine. Anal. Chem. 85 (2013) 5297. 

The IMS capability to simultaneously detect multiple metabolites at a time, even with spatial information, facilitates this emerging technique as an effective tool for biomarker discovery, within surgically resected tissues. In fact, a previous study has shown that IMS can discriminate cancer types (such as primary or nonprimary cancer) based on their molecular signature, and can even predict survival rate among human patients [77]. For this kind of purpose, it is necessary to utilize statistical analyses to extract useful information from enormous IMS data sets. The MS of tissues gives an extremely complex spectrum with hundreds of to a thousand peaks obtained from a single data point, and... 

S. L. Robinette, J. C. Lindon and J. K. Nicholson, Statistical Spectroscopic Tools for Biomarker Discovery and Systems Medicine, Anal Chem., 2013, 85, 5297. 

It is therefore not surprising that the interest in PyMS as a typing tool diminished at the turn of the twenty-first century and hence why taxonomists have turned to MS-based methods that use soft ionization methods such as electrospray ionization (ESI-MS) and matrix-assisted laser desorption ionization (MALDI MS). These methods generate information-rich spectra of metabolites and proteins, and because the molecular ion is seen, the potential for biomarker discovery is being realized. The analyses of ESI-MS and MALDI-MS data will still need chemometric methods, and it is hoped that researchers in these areas can look back and learn from the many PyMS studies where machine learning was absolutely necessary to turn the complex pyrolysis MS data into knowledge of bacterial identities. 

Over the past few years, the ProteinChip System has proven to be a valuable tool for the discovery and validation of newly detected protein biomarker patterns. It is used by more than 1000 customers worldwide, including academic and governmen-... 

Quantification in omics generally falls into two categories, i.e., relative and absolute quantifications. The former measures the pattern change of the lipid species in a lipidome, which can be used as a tool for readout after stimulation or for biomarker discovery. The latter determines the mass levels of individual lipid species, and then each individual lipid subclass and class of a lipidome. Measurement of the changed mass levels of individual lipid elass, subelass, and molecular species is critical for elucidation of biochemical mechanism(s) responsible for the changes and for path-way/network analysis in addition to serving as a tool for readout after a perturbation or for biomarker diseovery. Thus, only the latter case is extensively discussed in this and the following chapters. 

Servais, A. C., Crommen, J., and Fillet, M. (2006). Capillary electrophoresis-mass spectrometry, an attractive tool for drug bioanalysis and biomarker discovery. Electrophoresis 27, 2616—2629. 

Microarrays have become robust, reliable research tools that enable researchers to screen for a multitude of parameters using minimal amounts of sample material. The acceptance of protein microarrays is growing constantly they have already been demonstrated to be useful tools in disease-related biomarker discovery. In addition, protein microarrays have been introduced into clinical trials in order to investigate the potential adverse effects of drug candidates. Depending on the number of validated disease-specific biomarkers, as well as on their therapeutic relevance, such assays are performed either on a protein microarray or a bead-based platform. 

Aleo MD, Navetta KA, Emeigh Hart SG et al. (2002) Mechanism-based urinary biomarkers of aminoglycoside-induced phospholipidosis. Comp Clin Pathol 11 193-194 Aleo MD, Navetta KA, Emeigh Hart SG et al. (2003) Mechanism-based urinary biomarkers of renal phospholipidosis and injury. Toxicol Sci 72 (Suppl) 243 Bandara LR, Kennedy S (2002) Toxicoproteomics - a new pre-clinical tool. Drug Disc Today 7 411—418 Chapman K (2002) The ProteinChip biomarker system from Ci-phergen Biosystems a novel proteomics platform for rapid biomarker discovery and validation. Biochem Soci Trans 30 82-87... 

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