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Mass Spectrometry for Biomarker Development

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General Methods in Biomarker Research and their Applications

Abstract

Biomarkers potentially play a crucial role in early disease diagnosis, prognosis, and targeted therapy. In the past decade, mass spectrometry-based proteomics has become increasingly important in biomarker development due to large advances in technology and associated methods. This chapter mainly focuses on the application of broad (e.g., shotgun) proteomics in biomarker discovery and the utility of targeted proteomics in biomarker verification and validation. A range of mass spectrometry methodologies are discussed emphasizing their efficacy across the different stages of biomarker development, with a particular emphasis on blood-based biomarker development.

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Abbreviations

2-DE:

Two-Dimensional Gel Electrophoresis

AMT:

Accurate Mass and Time Tag

APEX:

Absolute Protein Expression

AQUA:

Absolute Quantification

CDIT:

Culture-Derived Isotope Tag

CID:

Collision-Induced Dissociation

ECD:

Electron Capture Dissociation

ELISA:

Enzyme-Linked Immunosorbent Assay

emPAI:

Exponentially Modified Protein Abundance Index

ESI:

Electrospray Ionization

ETD:

Electron Transfer Dissociation

FAIMS:

Field Asymmetric Waveform Ion Mobility Spectrometry

FDR:

False Discovery Rate

HCD:

High-Energy Collisional Dissociation

HILIC:

Hydrophilic Interaction Liquid Chromatography

iBAQ:

Intensity-Based Absolute Quantification

ICAT:

Isotope-Coded Affinity Tag

ICPL:

Isotope-Coded Protein Labeling

IEF:

Isoelectric Focusing

IMAC:

Immobilized Metal Ion Affinity Chromatography

IMS:

Ion Mobility Spectrometry

iTRAQ:

Isobaric Tag for Relative and Absolute Quantification

LC:

Liquid Chromatography

LC-MS/MS:

Liquid Chromatography-Tandem Mass Spectrometry

LOD:

Limit of Detection

LOQ:

Limit of Quantification

MALDI:

Matrix-Assisted Laser Desorption Ionization

MRM:

Multiple Reaction Monitoring

MS:

Mass Spectrometry

MS/MS:

Tandem Mass Spectrometry

MudPIT:

Multidimensional Protein Identification Technology

PAC:

Phosphoramidate Chemistry

PrEst:

Protein Epitope Signature Tag

PRISM:

High-Pressure, High-Resolution Separations Coupled with Intelligent Selection and Multiplexing

PRM:

Parallel Reaction Monitoring

PSAQ:

Protein Synthesis Absolute Quantification

PSM:

Peptide Spectrum Match

PTM:

Posttranslational Modification

QconCAT:

Quantification Concatemers

RP:

Reversed Phase

SAX:

Strong Anion Exchange

SCX:

Strong Cation Exchange

SID:

Stable Isotope Dilution

SIL:

Stable Isotope Labeling

SILAC:

Stable Isotope Labeling by Amino Acids in Cell Culture

SIN:

Spectral Index

SISCAPA:

Stable Isotope Standards and Capture by Anti-Peptide Antibodies

SPIN:

Subambient Pressure Ionization with Nano-electrospray Source

SRM:

Selected Reaction Monitoring

SRM3 :

Selected Reaction Monitoring Cubed

SWATH:

Sequential Window Acquisition of All Theoretical Fragment-Ion Spectra

TMT:

Tandem Mass Tag

References

  • Addona TA, Shi X, Keshishian H, et al. A pipeline that integrates the discovery and verification of plasma protein biomarkers reveals candidate markers for cardiovascular disease. Nat Biotechnol. 2011;29:635–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Adkins JN, Varnum SM, Auberry KJ, et al. Toward a human blood serum proteome: analysis by multidimensional separation coupled with mass spectrometry. Mol Cell Proteomics. 2002;1:947–55.

    Article  CAS  PubMed  Google Scholar 

  • Aebersold R, Burlingame AL, Bradshaw RA. Western blots vs. SRM assays: time to turn the tables? Mol Cell Proteomics. 2013;12:2381–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anderson NL. The clinical plasma proteome: a survey of clinical assays for proteins in plasma and serum. Clin Chem. 2010;56:177–85.

    Article  CAS  PubMed  Google Scholar 

  • Anderson NL, Anderson NG. The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics. 2002;1:845–67.

    Article  CAS  PubMed  Google Scholar 

  • Anderson NL, Anderson NG, Haines LR, et al. Mass spectrometric quantitation of peptides and proteins using Stable Isotope Standards and Capture by Anti-Peptide Antibodies (SISCAPA). J Proteome Res. 2004;3:235–44.

    Article  CAS  PubMed  Google Scholar 

  • Arike L, Valgepea K, Peil L, et al. Comparison and applications of label-free absolute proteome quantification methods on Escherichia coli. J Proteomics. 2012;75:5437–48.

    Article  CAS  PubMed  Google Scholar 

  • Baker ES, Livesay EA, Orton DJ, et al. An LC-IMS-MS platform providing increased dynamic range for high-throughput proteomic studies. J Proteome Res. 2010;9:997–1006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Becker JO, Hoofnagle AN. Replacing immunoassays with tryptic digestion-peptide immunoaffinity enrichment and LC-MS/MS. Bioanalysis. 2012;4:281–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69:89–95.

    Article  Google Scholar 

  • Bogdanov B, Smith RD. Proteomics by FTICR mass spectrometry: top down and bottom up. Mass Spectrom Rev. 2005;24:168–200.

    Article  CAS  PubMed  Google Scholar 

  • Bordeaux J, Welsh A, Agarwal S, et al. Antibody validation. Biotechniques. 2010;48:197–209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brownridge P, Beynon RJ. The importance of the digest: proteolysis and absolute quantification in proteomics. Methods. 2011;54:351–60.

    Article  CAS  PubMed  Google Scholar 

  • Brun V, Masselon C, Garin J, et al. Isotope dilution strategies for absolute quantitative proteomics. J Proteomics. 2009;72:740–9.

    Article  CAS  PubMed  Google Scholar 

  • Conrads TP, Anderson GA, Veenstra TD, et al. Utility of accurate mass tags for proteome-wide protein identification. Anal Chem. 2000;72:3349–54.

    Article  CAS  PubMed  Google Scholar 

  • Domon B, Aebersold R. Mass spectrometry and protein analysis. Science. 2006;312:212–7.

    Article  CAS  PubMed  Google Scholar 

  • Domon B, Aebersold R. Options and considerations when selecting a quantitative proteomics strategy. Nat Biotechnol. 2010;28:710–21.

    Article  CAS  PubMed  Google Scholar 

  • Dunham WH, Mullin M, Gingras AC. Affinity-purification coupled to mass spectrometry: basic principles and strategies. Proteomics. 2012;12:1576–90.

    Article  CAS  PubMed  Google Scholar 

  • Elias JE, Gygi SP. Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry. Nat Methods. 2007;4:207–14.

    Article  CAS  PubMed  Google Scholar 

  • Everley RA, Kunz RC, McAllister FE, et al. Increasing throughput in targeted proteomics assays: 54-plex quantitation in a single mass spectrometry run. Anal Chem. 2013;85:5340–6.

    Article  CAS  PubMed  Google Scholar 

  • Farrah T, Deutsch EW, Omenn GS, et al. A high-confidence human plasma proteome reference set with estimated concentrations in PeptideAtlas. Mol Cell Proteomics. 2011;10:M110 006353.

    Article  PubMed  PubMed Central  Google Scholar 

  • Fortin T, Salvador A, Charrier JP, et al. Multiple reaction monitoring cubed for protein quantification at the low nanogram/milliliter level in nondepleted human serum. Anal Chem. 2009;81:9343–52.

    Article  CAS  PubMed  Google Scholar 

  • Frese CK, Altelaar AF, Hennrich ML, et al. Improved peptide identification by targeted fragmentation using CID, HCD and ETD on an LTQ-Orbitrap Velos. J Proteome Res. 2011;10:2377–88.

    Article  CAS  PubMed  Google Scholar 

  • Gale DC, Smith RD. Small volume and low flow-rate electrospray ionization mass spectrometry of aqueous samples. Rapid Commun Mass Spectrom. 1993;7:1017–21.

    Article  CAS  Google Scholar 

  • Gallien S, Duriez E, Crone C, et al. Targeted proteomic quantification on quadrupole-orbitrap mass spectrometer. Mol Cell Proteomics. 2012;11:1709–23.

    Article  PubMed  PubMed Central  Google Scholar 

  • Geiger T, Wehner A, Schaab C, et al. Comparative proteomic analysis of eleven common cell lines reveals ubiquitous but varying expression of most proteins. Mol Cell Proteomics. 2012;11:M111 014050.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gillet LC, Navarro P, Tate S, 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gouw JW, Krijgsveld J, Heck AJ. Quantitative proteomics by metabolic labeling of model organisms. Mol Cell Proteomics. 2010;9:11–24.

    Article  CAS  PubMed  Google Scholar 

  • Hawkridge AM, Muddiman DC. Mass spectrometry-based biomarker discovery: toward a global proteome index of individuality. Annu Rev Anal Chem. 2009;2:265–77.

    Article  CAS  Google Scholar 

  • Hebert AS, Merrill AE, Bailey DJ, et al. Neutron-encoded mass signatures for multiplexed proteome quantification. Nat Methods. 2013;10:332–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoofnagle AN, Wener MH. The fundamental flaws of immunoassays and potential solutions using tandem mass spectrometry. J Immunol Methods. 2009;347:3–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huttenhain R, Soste M, Selevsek N, et al. Reproducible quantification of cancer-associated proteins in body fluids using targeted proteomics. Sci Transl Med. 2012;4:142ra194.

    Article  Google Scholar 

  • Jaros JA, Guest PC, Bahn S, et al. Affinity depletion of plasma and serum for mass spectrometry-based proteome analysis. Methods Mol Biol. 2013;1002:1–11.

    Article  CAS  PubMed  Google Scholar 

  • Keller A, Nesvizhskii AI, Kolker E, et al. Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS and database search. Anal Chem. 2002;74:5383–92.

    Article  CAS  PubMed  Google Scholar 

  • Keshishian H, Addona T, Burgess M, et al. Quantitative, multiplexed assays for low abundance proteins in plasma by targeted mass spectrometry and stable isotope dilution. Mol Cell Proteomics. 2007;6:2212–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Keshishian H, Addona T, Burgess M, et al. Quantification of cardiovascular biomarkers in patient plasma by targeted mass spectrometry and stable isotope dilution. Mol Cell Proteomics. 2009;8:2339–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim JW, You J. Protein target quantification decision tree. Int J Proteomics. 2013;2013:701247.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kuhn E, Whiteaker JR, Mani DR, et al. Interlaboratory evaluation of automated, multiplexed peptide immunoaffinity enrichment coupled to multiple reaction monitoring mass spectrometry for quantifying proteins in plasma. Mol Cell Proteomics. 2012;11:M111 013854.

    Article  PubMed  Google Scholar 

  • Lange V, Picotti P, Domon B, et al. Selected reaction monitoring for quantitative proteomics: a tutorial. Mol Syst Biol. 2008;4:222.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lewin DA, Weiner MP. Molecular biomarkers in drug development. Drug Discov Today. 2004;9:976–83.

    Article  CAS  PubMed  Google Scholar 

  • Lisacek F, Cohen-Boulakia S, Appel RD. Proteome informatics II: bioinformatics for comparative proteomics. Proteomics. 2006;6:5445–66.

    Article  CAS  PubMed  Google Scholar 

  • Liu T, Qian WJ, Gritsenko MA, et al. High dynamic range characterization of the trauma patient plasma proteome. Mol Cell Proteomics. 2006a;5:1899–913.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu T, Qian WJ, Mottaz HM, et al. Evaluation of multiprotein immunoaffinity subtraction for plasma proteomics and candidate biomarker discovery using mass spectrometry. Mol Cell Proteomics. 2006b;5:2167–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu T, Belov ME, Jaitly N, et al. Accurate mass measurements in proteomics. Chem Rev. 2007;107:3621–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • MacLean B, Tomazela DM, Shulman N, et al. Skyline: an open source document editor for creating and analyzing targeted proteomics experiments. Bioinformatics. 2010;26:966–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martinovic S, Veenstra TD, Anderson GA, et al. Selective incorporation of isotopically labeled amino acids for identification of intact proteins on a proteome-wide level. J Mass Spectrom. 2002;37:99–107.

    Article  PubMed  Google Scholar 

  • Mason EA, McDaniel EW. Introduction, in Transport properties of ions in gases. Wiley-VCH; Weinheim, Germany; 2005. p. 1–29.

    Google Scholar 

  • McDonald WH, Yates 3rd JR. Shotgun proteomics and biomarker discovery. Dis Markers. 2002;18:99–105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mertins P, Qiao JW, Patel J, et al. Integrated proteomic analysis of post-translational modifications by serial enrichment. Nat Methods. 2013;10:634–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nesvizhskii AI, Keller A, Kolker E, et al. A statistical model for identifying proteins by tandem mass spectrometry. Anal Chem. 2003;75:4646–58.

    Article  CAS  PubMed  Google Scholar 

  • Omenn GS, States DJ, Adamski M, et al. Overview of the HUPO plasma proteome project: results from the pilot phase with 35 collaborating laboratories and multiple analytical groups, generating a core dataset of 3020 proteins and a publicly-available database. Proteomics. 2005;5:3226–45.

    Article  CAS  PubMed  Google Scholar 

  • Ong SE, Mann M. Mass spectrometry-based proteomics turns quantitative. Nat Chem Biol. 2005;1:252–62.

    Article  CAS  PubMed  Google Scholar 

  • Ong SE, Blagoev B, Kratchmarova I, et al. Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics. 2002;1:376–86.

    Article  CAS  PubMed  Google Scholar 

  • Picard G, Lebert D, Louwagie M, et al. PSAQ standards for accurate MS-based quantification of proteins: from the concept to biomedical applications. J Mass Spectrom. 2012;47:1353–63.

    Article  CAS  PubMed  Google Scholar 

  • Picotti P, Aebersold R. Selected reaction monitoring-based proteomics: workflows, potential, pitfalls and future directions. Nat Methods. 2012;9:555–66.

    Article  CAS  PubMed  Google Scholar 

  • Polaskova V, Kapur A, Khan A, et al. High-abundance protein depletion: comparison of methods for human plasma biomarker discovery. Electrophoresis. 2010;31:471–82.

    Article  CAS  PubMed  Google Scholar 

  • Pratt JM, Simpson DM, Doherty MK, et al. Multiplexed absolute quantification for proteomics using concatenated signature peptides encoded by QconCAT genes. Nat Protoc. 2006;1:1029–43.

    Article  CAS  PubMed  Google Scholar 

  • Qian WJ, Monroe ME, Liu T, et al. Quantitative proteome analysis of human plasma following in vivo lipopolysaccharide administration using 16O/18O labeling and the accurate mass and time tag approach. Mol Cell Proteomics. 2005;4:700–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qian WJ, Kaleta DT, Petritis BO, et al. Enhanced detection of low abundance human plasma proteins using a tandem IgY12-SuperMix immunoaffinity separation strategy. Mol Cell Proteomics. 2008;7:1963–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rafalko A, Dai S, Hancock WS, et al. Development of a chip/chip/SRM platform using digital chip isoelectric focusing and LC-chip mass spectrometry for enrichment and quantitation of low abundance protein biomarkers in human plasma. J Proteome Res. 2012;11:808–17.

    Article  CAS  PubMed  Google Scholar 

  • Ransohoff DF. Bias as a threat to the validity of cancer molecular-marker research. Nat Rev Cancer. 2005;5:142–9.

    Article  CAS  PubMed  Google Scholar 

  • Rifai N, Gillette MA, Carr SA. Protein biomarker discovery and validation: the long and uncertain path to clinical utility. Nat Biotechnol. 2006;24:971–83.

    Article  CAS  PubMed  Google Scholar 

  • Rodland KD, Maihle NJ. Searching for a system: the quest for ovarian cancer biomarkers. Cancer Biomark: Sect A Dis Markers. 2010;8:223–30.

    CAS  Google Scholar 

  • Schmidt A, Kellermann J, Lottspeich F. A novel strategy for quantitative proteomics using isotope-coded protein labels. Proteomics. 2005;5:4–15.

    Article  CAS  PubMed  Google Scholar 

  • Shi T, Fillmore TL, Sun X, et al. Antibody-free, targeted mass-spectrometric approach for quantification of proteins at low picogram per milliliter levels in human plasma/serum. Proc Natl Acad Sci U S A. 2012a;109:15395–400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi T, Su D, Liu T, et al. Advancing the sensitivity of selected reaction monitoring-based targeted quantitative proteomics. Proteomics. 2012b;12:1074–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi T, Sun X, Gao Y, et al. Targeted quantification of low ng/mL level proteins in human serum without immunoaffinity depletion. J Proteome Res. 2013;12:3353–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sitaraman K, Chatterjee DK. High-throughput protein expression using cell-free system. Methods Mol Biol. 2009;498:229–44.

    Article  CAS  PubMed  Google Scholar 

  • Smith RD. Mass spectrometry in biomarker applications: from untargeted discovery to targeted verification, and implications for platform convergence and clinical application. Clin Chem. 2012;58:528–30.

    Article  CAS  PubMed  Google Scholar 

  • Smith RD, Anderson GA, Lipton MS, et al. An accurate mass tag strategy for quantitative and high-throughput proteome measurements. Proteomics. 2002;2:513–23.

    Article  CAS  PubMed  Google Scholar 

  • Smith RD, Shen Y, Tang K. Ultrasensitive and quantitative analyses from combined separations-mass spectrometry for the characterization of proteomes. Acc Chem Res. 2004;37:269–78.

    Article  CAS  PubMed  Google Scholar 

  • Stahl-Zeng J, Lange V, Ossola R, et al. High sensitivity detection of plasma proteins by multiple reaction monitoring of N-glycosites. Mol Cell Proteomics. 2007;6:1809–17.

    Article  CAS  PubMed  Google Scholar 

  • States DJ, Omenn GS, Blackwell TW, et al. Challenges in deriving high-confidence protein identifications from data gathered by a HUPO plasma proteome collaborative study. Nat Biotechnol. 2006;24:333–8.

    Article  CAS  PubMed  Google Scholar 

  • Swaney DL, Wenger CD, Thomson JA, et al. Human embryonic stem cell phosphoproteome revealed by electron transfer dissociation tandem mass spectrometry. Proc Natl Acad Sci U S A. 2009;106:995–1000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang K, Page JS, Marginean I, et al. Improving liquid chromatography-mass spectrometry sensitivity using a subambient pressure ionization with nanoelectrospray (SPIN) interface. J Am Soc Mass Spectrom. 2011;22:1318–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ting L, Rad R, Gygi SP, et al. MS3 eliminates ratio distortion in isobaric multiplexed quantitative proteomics. Nat Methods. 2011;8:937–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tran JC, Zamdborg L, Ahlf DR, et al. Mapping intact protein isoforms in discovery mode using top-down proteomics. Nature. 2011;480:254–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Washburn MP, Wolters D, Yates 3rd JR. Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat Biotechnol. 2001;19:242–7.

    Article  CAS  PubMed  Google Scholar 

  • Wenger CD, Lee MV, Hebert AS, et al. Gas-phase purification enables accurate, multiplexed proteome quantification with isobaric tagging. Nat Methods. 2011;8:933–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Whiteaker JR, Zhao L, Anderson L, et al. An automated and multiplexed method for high throughput peptide immunoaffinity enrichment and multiple reaction monitoring mass spectrometry-based quantification of protein biomarkers. Mol Cell Proteomics. 2010;9:184–96.

    Article  CAS  PubMed  Google Scholar 

  • Whiteaker JR, Lin C, Kennedy J, et al. A targeted proteomics-based pipeline for verification of biomarkers in plasma. Nat Biotechnol. 2011;29:625–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilm M, Mann M. Analytical properties of the nanoelectrospray ion source. Anal Chem. 1996;68:1–8.

    Article  CAS  PubMed  Google Scholar 

  • Wisniewski JR, Dus K, Mann M. Proteomic workflow for analysis of archival formalin-fixed and paraffin-embedded clinical samples to a depth of 10 000 proteins. Proteomics Clin Appl. 2013;7:225–33.

    Article  CAS  PubMed  Google Scholar 

  • Wu C, Wei W, Li C, et al. Delicate analysis of post-translational modifications on Dishevelled 3. J Proteome Res. 2012;11:3829–37.

    Article  CAS  PubMed  Google Scholar 

  • Wulfkuhle JD, Liotta LA, Petricoin EF. Proteomic applications for the early detection of cancer. Nat Rev Cancer. 2003;3:267–75.

    Article  CAS  PubMed  Google Scholar 

  • Xie F, Liu T, Qian WJ, et al. Liquid chromatography-mass spectrometry-based quantitative proteomics. J Biol Chem. 2011;286:25443–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yates JR, Ruse CI, Nakorchevsky A. Proteomics by mass spectrometry: approaches, advances, and applications. Annu Rev Biomed Eng. 2009;11:49–79.

    Article  CAS  PubMed  Google Scholar 

  • Zhao Y, Jensen ON. Modification-specific proteomics: strategies for characterization of post-translational modifications using enrichment techniques. Proteomics. 2009;9:4632–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu W, Smith JW, Huang CM. Mass spectrometry-based label-free quantitative proteomics. J Biomed Biotechnol. 2010;2010:840518.

    PubMed  Google Scholar 

  • Zimmer JS, Monroe ME, Qian WJ, et al. Advances in proteomics data analysis and display using an accurate mass and time tag approach. Mass Spectrom Rev. 2006;25:450–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

Portions of this work were supported by grants from the National Institutes of Health National Cancer Institute (U24 CA160019 and Interagency Agreement ACN12003-001-00000) and National Institute of General Medical Sciences (P41 GM103493). The research was performed at the Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by the Department of Energy (DOE) Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory, which is operated by Battelle Memorial Institute for the DOE under Contract DE-AC05-76RL0 1830.

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Wu, C., Liu, T., Baker, E.S., Rodland, K.D., Smith, R.D. (2015). Mass Spectrometry for Biomarker Development. In: Preedy, V., Patel, V. (eds) General Methods in Biomarker Research and their Applications. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7696-8_21

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