Top-Down Mass Spectrometry for Protein Molecular Diagnostics and Biomarker Discovery

Steven M. Patrie*, Michael J. Roth, Junmei Zhang

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations

Abstract

Top-down mass spectrometry differs from the traditional bottom-up approach in that proteins are analyzed directly rather than enzymatically digested prior to analysis. Although the bottom-up approach tends to be faster and more readily implemented, the top-down approach has improved selectivity that enables simultaneous characterization of dynamic and hard-to-predict events such as coding polymorphisms, alternative splicing, and post-translational modifications, promising a clearer picture of biological variation that exists beyond gene translation. With the maturation of multidimensional sample processing procedures, data analysis tools, and "online" liquid chromatography and high-resolution mass spectrometry (LC/MS) technologies, top-down for proteomics investigations has emerged with sensitivity and dynamic range typically associated with peptide workflows. Top-down and bottom-up often provide complementary information; therefore, as the instrumentation used for bottom-up and top-down continues to merge, top-down is becoming more accessible to the general scientific community, allowing scientists to gain a more complete understanding of dynamic living systems.

Original languageEnglish (US)
Title of host publicationProteomic and Metabolomic Approaches to Biomarker Discovery
PublisherElsevier Inc
Pages313-332
Number of pages20
ISBN (Print)9780123944467
DOIs
StatePublished - Jan 1 2013

Keywords

  • Biomarkers
  • Chromatography
  • High-resolution
  • Mass spectrometry
  • Proteomics
  • Top-down

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Patrie, S. M., Roth, M. J., & Zhang, J. (2013). Top-Down Mass Spectrometry for Protein Molecular Diagnostics and Biomarker Discovery. In Proteomic and Metabolomic Approaches to Biomarker Discovery (pp. 313-332). Elsevier Inc. https://doi.org/10.1016/B978-0-12-394446-7.00020-0