Global and targeted quantitative proteomics for biomarker discovery

Veenstra, Timothy D.

doi:10.1016/j.jchromb.2006.09.004

Cited by 111 publications

(69 citation statements)

References 28 publications

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“…T he potential of proteomic tools ranges from biomarker discovery and clinical diagnostics to the provision of data for systems biology and fundamental biological research (1)(2)(3)(4)(5)(6). This broad range of applications is one of the drivers for the development of protein analysis tools with greater capability.…”

mentioning

confidence: 99%

Protein identification and quantification by two-dimensional infrared spectroscopy: Implications for an all-optical proteomic platform

Fournier¹,

Gardner

Kedra

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Electron-vibration-vibration two-dimensional coherent spectroscopy, a variant of 2DIR, is shown to be a useful tool to differentiate a set of 10 proteins based on their amino acid content. Twodimensional vibrational signatures of amino acid side chains are identified and the corresponding signal strengths used to quantify their levels by using a methyl vibrational feature as an internal reference. With the current apparatus, effective differentiation can be achieved in four to five minutes per protein, and our results suggest that this can be reduced to <1 min per protein by using the same technology. Finally, we show that absolute quantification of protein levels is relatively straightforward to achieve and discuss the potential of an all-optical high-throughput proteomic platform based on two-dimensional infrared spectroscopic measurements.2DIR ͉ amino acid ͉ bioinformatics ͉ vibrational T he potential of proteomic tools ranges from biomarker discovery and clinical diagnostics to the provision of data for systems biology and fundamental biological research (1-6). This broad range of applications is one of the drivers for the development of protein analysis tools with greater capability. Optical spectroscopies appear to have significant potential for protein analysis (7-9), but conventional approaches suffer from overcongested spectra, which makes feature assignment and quantification highly problematic. Multidimensional coherent infrared spectroscopic techniques, commonly referred to as twodimensional infrared (2DIR) spectroscopies, might be expected to be able to relieve the congestion of infrared spectra sufficiently to allow such assignment and quantification to take place. Indeed, we recently demonstrated how picosecond electronvibration-vibration (EVV) four-wave mixing experiments can decongest 2DIR spectra to an even greater extent (10, 11), and showed how such an EVV approach can be applied to the analysis of peptides (12). In this article we take the approach further to show that it can be used to differentiate and identify proteins and to measure absolute protein quantities. We also demonstrate that the sensitivity and throughput of our EVV 2DIR apparatus is sufficient for this method to be considered for use as a real proteomic tool.Although our previous work showed that it is possible to quantify relative amino acid levels for short peptides (12), there is always the possibility that primary, secondary, or tertiary structural effects would prevent such measurements on proteins.In this article we demonstrate that these structural sensitivities are not limiting factors either for differentiation/identification or for absolute quantification of protein levels.The key proposition of this article is that protein identification can be performed by using spectroscopically determined amino acid content, relative to an internal reference. Amino acid composition analysis is an approach that has been used to determine protein relatedness (13) and protein structural classes (14, 15). Although it is known that c...

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mentioning

confidence: 99%

Protein identification and quantification by two-dimensional infrared spectroscopy: Implications for an all-optical proteomic platform

Fournier¹,

Gardner

Kedra

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…Many technological improvements have made 2-DE relatively inexpensive and accessible to most biomedical research labs but criticisms such as the inability of 2D-PAGE to resolve membrane proteins and its lack of reproducibility have been to some extent tempered by the development of better reagents, techniques, and gel alignment software. Even though 2-DE is still limited in sensitivity and dynamic range (Veenstra, 2007), it is still the most widely used method for protein separation. Nonetheless, liquid chromatography methods which includes gel filtration, affinity chromatography, ion exchange chromatography, ReversePhase (RP) and High-Performance Liquid Chromatography (HPLC), and multidimensional chromatography are also used for protein separation in proteomic analysis (Mishra, 2010).…”

Section: Proteomics In Practicementioning

confidence: 99%

“…Several tools are available to help quantify and interpret data generated through specific applications of MS. MS-based quantitative approaches include tagging or chemical modification methods, such as isotope-coded affinity tags (ICAT), isobaric tag for relative and absolute quantitation (iTRAQ) or stable isotope labelling by amino acids in cell culture (SILAC). A further detailed description of proteomic techniques can be consulted in Hamacher et al, 2011;Mallick & Kuster, 2010;Mishra, 2010;Parker et al, 2010;Veenstra, 2007;Westermeier & Naven, 2002. Despite the variation in proteomics approaches, all techniques generate large quantities of data. Bioinformatics approaches appear as an essential mean for analysis, storage and retrieval of all that information.…”

Section: Proteomics In Practicementioning

confidence: 99%

“…This is a two-step process in which proteins within cellular extracts are first fractionated to reduce sample complexity, and then the proteins are identified by MS (Minden, 2007). Two-dimensional electrophoresis is the long-time standard for protein separation as it provides a direct method to visualize changes in proteins between complex proteome samples and is able to resolve thousands of proteins; however, it has suffered from poor reproducibility and limited sensitivity (Minden, 2007;Veenstra, 2007). DIGE was developed to overcome the reproducibility and sensitivity limitations and provides a reliable and sensitive platform to discover proteome changes in a boundless variety of circumstances (Minden, 2007).…”

Section: Comparative Proteomics and Antibacterial Drug Discovery Processmentioning

confidence: 99%

“…Proteomics has been contributing to a wide-range of scientific disciplines, but perhaps no area is more critical than the discovery of novel biomarkers. The extraordinary developments made in proteomic technologies in the past decade have enabled investigators to search for biomarkers by scanning complex proteome samples using unbiased methods (Veenstra, 2007). Currently, the search for protein biomarkers has been dominated by the employment of MS. Its high mass accuracy, resolution, dynamic range, sensitivity and even more importantly the speed at which MS/MS is performed, allowing thousands of proteins to be unambiguously identified, have made MS an invaluable tool for biomarker discovery (Blonder et al, 2011).…”

Section: Remarks On Proteomics As a Biomarker Search Toolmentioning

confidence: 99%

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