Targeted quantitative proteomic analyses aim at systematically measuring the abundance of proteins in large sets of samples, without biases or missing values. One typical implementation is the verification of biomarker candidates in bodily fluids, which measures extended lists of validated transitions using triple quadrupole instruments in selected reaction monitoring (SRM) mode. However, the selectivity of this mass spectrometer is limited by the resolving power of its mass analyzers, and interferences may require the reanalysis of the samples. Despite the efforts undertaken in the development of software, and resources to design SRM studies, and to analyze and validate the data, the process remains tedious and time consuming. The development of fast scanning high-resolution and accurate mass (HRAM) spectrometers, such as the quadrupole TOF and the quadrupole orbitrap instruments, offers alternatives for targeted analyses. The selectivity of HRAM measurements in complex samples is greatly improved by effectively separating co-eluting interferences. The fragment ion chromatograms are extracted from the high-resolution MS/MS data using a narrow mass tolerance. The entire process is straightforward as the selection of fragment ions is performed postacquisition. This account describes the different HRAM techniques and discusses their advantages and limitations in the context of targeted proteomic analyses.
As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.
|pmic8037-sup-0001-FigureS1.docx23.9 KB||Figure S1|
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
- 1, , , The cancer genome. Nature 2009, 458, 719–724.
- 2, , , et al., On the development of plasma protein biomarkers. J. Proteome Res. 2011, 10, 5–16.
- 3, , , , , High throughput protein characterization by automated reverse-phase chromatography/electrospray tandem mass spectrometry. Protein Sci. 1998, 7, 706–719.
- 4, , , , , Automated approach for quantitative analysis of complex peptide mixtures from tandem mass spectra. Nat. Method 2004, 1, 39–45.
- 5, , , High resolution mass spectrometry. Anal. Chem. 2012, 84, 708–719.
- 6, , , , Fourier transform mass spectrometry. Mol. Cell. Proteomics 2011, 10, M111.009431.
- 7, , , An introduction to quadrupole-time-of-flight mass spectrometry. J. Mass Spectrom. 2001, 36, 849–865.
- 8, , , , , Parallel reaction monitoring for high resolution and high mass accuracy quantitative, targeted proteomics. Mol. Cell. Proteomics 2012, 11, 1475–1488.
- 9, , , et al., Targeted proteomic quantification on quadrupole-orbitrap mass spectrometer. Mol. Cell. Proteomics 2012, 11, 1709–1723.
- 10, , , , , Resistively heated gas chromatography coupled to quadrupole mass spectrometry. J. Sep. Sci. 2002, 25, 608–614.
- 11, , , et al., Overcoming biofluid protein complexity during targeted mass spectrometry detection and quantification of protein biomarkers by MRM cubed (MRM3). Anal. Bioanal. Chem. 2014, 406, 1193–1200.
- 12, , , et al., The Orbitrap: a new mass spectrometer. J. Mass Spectrom. 2005, 40, 430–443.
- 13, , , , Accelerating spectral acquisition rate of Orbitrap mass spectrometry. Proceedings of the 58th Conference of the American Society for Mass Spectrometry 2010, Salt Lake City, USA.
- 14, , , Performance evaluation of a high-field Orbitrap mass analyzer. J. Am. Soc. Mass Spectrom. 2009, 20, 1391–1396.
- 15, , , et al., Mass spectrometry-based proteomics using Q Exactive, a high-performance benchtop quadrupole Orbitrap mass spectrometer. Mol. Cell. Proteomics 2011, 10, M111. 011015.
- 16, , , , , Performance characteristics of a new hybrid quadrupole time-of-flight tandem mass spectrometer (TripleTOF 5600). Anal. Chem. 2011, 83, 5442–5446.
- 17, , , Large-molecule quantification: sensitivity and selectivity head-to-head comparison of triple quadrupole with Q-TOF. Bioanalysis 2013, 5, 1181–1193.
- 18, , Selected ion fragmentation with a tandem quadrupole mass-spectrometer. J. Am. Chem. Soc. 1978, 100, 2274–2275.
- 19, , , Comparing similar spectra: from similarity index to spectral contrast angle. J. Am. Soc. Mass Spectrom. 2002, 13, 85–88.
- 20, , , , , Analysis of peptide MS/MS spectra from large-scale proteomics experiments using spectrum libraries. Anal. Chem. 2006, 78, 5678–5684.
- 21, , , , Technical considerations for large-scale parallel reaction monitoring analysis. J. Proteomics 2014, 100, 147–159.
- 22, , , et al., Comparison of triple quadrupole and high-resolution TOF-MS for quantification of peptides. Bioanalysis 2012, 4, 565–579.
- 23, , , et al., High sensitivity detection of plasma proteins by multiple reaction monitoring of N-glycosites. Mol. Cell. Proteomics 2007, 6, 1809–1817.
- 24, , , et al., Highly multiplexed targeted proteomics using precise control of peptide retention time. Proteomics 2012, 12, 1122–1133.
- 25, , , , Peptides quantification by liquid chromatography with matrix-assisted laser desorption/ionization and selected reaction monitoring detection. J. Proteome Res. 2012, 11, 4972–4982.
- 26, , , Advantages of application of UPLC in pharmaceutical analysis. Talanta 2006, 68, 908–918.
- 27, , , , Fast high performance liquid chromatography separations for proteomic applications using Fused-Core(R) silica particles. J. Chromatogr. A 2012, 1228, 232–241.
- 28, , , , Coupling ultra high-pressure liquid chromatography with mass spectrometry: constraints and possible applications. J. Chromatogr. A 2013, 1292, 2–18.
- 29, , , , , Combining immuno affinity purification and fast LC-MS to characterize peptide isoforms of diagnostic cancer markers. Proceedings of 62nd ASMS Conference on Mass Spectrometry. Allied Top., Baltimore, MD 2014.
- 30, , , , , Comparison of standard- and nano-flow liquid chromatography platforms for MRM-based quantitation of putative plasma biomarker proteins. Anal. Bioanal. Chem. 2012, 404, 1089–1101.
- 31, , , , Standardized protocols for quality control of MRM-based plasma proteomic workflows. J. Proteome Res. 2013, 12, 222–233.
- 32, , , A simple protocol to routinely assess the uniformity of proteomics analyses. J. Proteome Res. 2014, 13, 2688–2695.
- 33, , , et al., Isotope-labeled protein standards: toward absolute quantitative proteomics. Mol. Cell. Proteomics 2007, 6, 2139–2149.
- 34, , , , , Super-SILAC mix for quantitative proteomics of human tumor tissue. Nat. Methods 2010, 7, 383–385.
- 35, , , Selected reaction monitoring applied to proteomics. J. Mass Spectrom. 2011, 46, 298–312.
- 36, , , et al., Effect of collision energy optimization on the measurement of peptides by selected reaction monitoring (SRM) mass spectrometry. Anal. Chem. 2010, 82, 10116–10124.
- 37, , , Energy dependence of HCD on peptide fragmentation: stepped collisional energy finds the sweet spot. J. Am. Soc. Mass Spectrom. 2013, 24, 1690–1699.
- 38, , , et al., Skyline: an open source document editor for creating and analyzing targeted proteomics experiments. Bioinformatics 2010, 26, 966–968.
- 39, , , et al., CONSeQuence: prediction of reference peptides for absolute quantitative proteomics using consensus machine learning approaches. Mol. Cell. Proteomics 2011, 10, M110.003384.
- 40, , , et al., The PeptideAtlas project. Nucleic Acids Res. 2006, 34, D655–D658.
- 41, , , , Selectivity of LC-MS/MS analysis: implication for proteomics experiments. J. Proteomics 2013, 81, 148–158.
- 42, , , et al., Comparison of targeted peptide quantification assays for reductive dehalogenases by selective reaction monitoring (SRM) and precursor reaction monitoring (PRM). Anal. Bioanal. Chem. 2014, 406, 283–291.
- 43, , , et al., Parallel reaction monitoring (PRM) and selected reaction monitoring (SRM) exhibit comparable linearity, dynamic range and precision for targeted quantitative HDL proteomics. J. Proteomics 2015, 113, 388–399.
- 44, , , et al., Multiplexed parallel reaction monitoring targeting histone modifications on the Qexactive mass spectrometer. Anal. Chem. 2014, 86, 5526–5534.
- 45, , , et al., Global chromatin profiling reveals NSD2 mutations in pediatric acute lymphoblastic leukemia. Nat. Genet. 2013, 45, 1386–1391.
- 46, , , The parallel reaction monitoring method contributes to a highly sensitive polyubiquitin chain quantification. Biochem. Biophys. Res. Commun. 2013, 436, 223–229.
- 47, , , et al., Targeted data extraction of the MS/MS spectra generated by data-independent acquisition: a new concept for consistent and accurate proteome analysis. Mol. Cell. Proteomics 2012, 11, O111 016717.
- 48, , , et al., Conserved peptide fragmentation as a benchmarking tool for mass spectrometers and a discriminating feature for targeted proteomics. Mol. Cell. Proteomics 2014, 13, 2056–2071.
- 49, , , Proteomics on an Orbitrap benchtop mass spectrometer using all-ion fragmentation. Mol. Cell. Proteomics 2010, 9, 2252–2261.
- 50, , , et al., Software for quantitative proteomic analysis using stable isotope labeling and data independent acquisition. Anal. Chem. 2011, 83, 6971–6979.
- 51, , , , Effects of traveling wave ion mobility separation on data independent acquisition in proteomics studies. J. Proteome Res. 2013, 12, 2323–2339.
- 52, , , et al., Quantitative measurements of N-linked glycoproteins in human plasma by SWATH-MS. Proteomics 2013, 13, 1247–1256.
- 53, , , et al., Multiplexed MS/MS for improved data-independent acquisition. Nat. Methods 2013, 10, 744–746.
- 54, , , High-resolution MS in regulated bioanalysis: where are we now and where do we go from here? Bioanalysis 2013, 5, 1277–1284.
- 55, , , , , Analysis of biopharmaceutical proteins in biological matrices by LC-MS/MS I. Sample preparation. TrAC Trends Anal. Chem. 2013, 48, 41–51.