Spectroscopy July 2011 - Supplement - (Page 18)
18 Current Trends in Mass Spectrometry
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Advanced Structural Mass Spectrometry for Systems Biology: Pulling the Needles from Haystacks
Systems-wide measurements in life sciences research have considerable promise in areas ranging from personalized medicine to understanding dominant or prevailing biological processes. However, formidable challenges remain in the comprehensive analyses of complex living systems, such as the necessity for detection limits that encompass wide concentration dynamic ranges while maintaining molecular specificity, sensitivity, and throughput. Recent work has demonstrated the ability to address several of these challenges with multidimensional separations using gas-phase ion mobility–mass spectrometry (IM-MS). IM-MS provides the capability to analyze a wide breadth of biomolecular classes on a single instrument simultaneously by separating the molecules according to their apparent surface area (equating roughly to their size) as well as their mass-to-charge ratio. The addition of a size separation parameter distributes the molecular classes into different regions of conformation space based upon differences in the prevailing intermolecular folding forces. This distribution negates the predominance of endogenous and exogenous matrix interferences experienced with traditional MS and provides a rapid (millisecond) means for separating biomolecules similar to liquid chromatography (LC)–MS approaches. Because separations are performed following ionization, additional dimensions of molecular information can be obtained through combining LC–IM-MS and gas chromatography (GC)–IM-MS. In this report, IM-MS is outlined as a separations method, several examples of the utility of IM-MS for complex biological measurements are illustrated, and the implications of this approach for systems biology research are discussed.
Jeffrey R. Enders, Cody R. Goodwin, Christina C. Marasco, Kevin T. Seale, John P. Wikswo, and John A. McLean
ystems biology seeks to describe the function of a biological system using a holistic, multiscale approach. This approach encompasses the analyses of molecular classes such as the genome, transcriptome, proteome, and metabolome (among others) of a biological system. Most modern approaches choose to either rapidly
sample a single aspect (for example, the electrochemical detection of glucose and the use of green fluorescent protein as a means of monitoring translation) or infrequently sample a more comprehensive set of data. Intermittent sampling results in a fractional snapshot of the system, upon which biological inferences must be placed. When
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