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- Volume 9, 2016
Annual Review of Analytical Chemistry - Volume 9, 2016
Volume 9, 2016
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Mass Spectrometry as a Preparative Tool for the Surface Science of Large Molecules
Vol. 9 (2016), pp. 473–498More LessMeasuring and understanding the complexity that arises when nanostructures interact with their environment are one of the major current challenges of nanoscale science and technology. High-resolution microscopy methods such as scanning probe microscopy have the capacity to investigate nanoscale systems with ultimate precision, for which, however, atomic scale precise preparation methods of surface science are a necessity. Preparative mass spectrometry (pMS), defined as the controlled deposition of m/z filtered ion beams, with soft ionization sources links the world of large, biological molecules and surface science, enabling atomic scale chemical control of molecular deposition in ultrahigh vacuum (UHV). Here we explore the application of high-resolution scanning probe microscopy and spectroscopy to the characterization of structure and properties of large molecules. We introduce the fundamental principles of the combined experiments electrospray ion beam deposition and scanning tunneling microscopy. Examples for the deposition and investigation of single particles, for layer and film growth, and for the investigation of electronic properties of individual nonvolatile molecules show that state-of-the-art pMS technology provides a platform analog to thermal evaporation in conventional molecular beam epitaxy. Additionally, it offers additional, unique features due to the use of charged polyatomic particles. This new field is an enormous sandbox for novel molecular materials research and demands the development of advanced molecular ion beam technology.
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Progress in Top-Down Proteomics and the Analysis of Proteoforms
Vol. 9 (2016), pp. 499–519More LessFrom a molecular perspective, enactors of function in biology are intact proteins that can be variably modified at the genetic, transcriptional, or post-translational level. Over the past 30 years, mass spectrometry (MS) has become a powerful method for the analysis of proteomes. Prevailing bottom-up proteomics operates at the level of the peptide, leading to issues with protein inference, connectivity, and incomplete sequence/modification information. Top-down proteomics (TDP), alternatively, applies MS at the proteoform level to analyze intact proteins with diverse sources of intramolecular complexity preserved during analysis. Fortunately, advances in prefractionation workflows, MS instrumentation, and dissociation methods for whole-protein ions have helped TDP emerge as an accessible and potentially disruptive modality with increasingly translational value. In this review, we discuss technical and conceptual advances in TDP, along with the growing power of proteoform-resolved measurements in clinical and translational research.
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Proteogenomics: Integrating Next-Generation Sequencing and Mass Spectrometry to Characterize Human Proteomic Variation
Vol. 9 (2016), pp. 521–545More LessMass spectrometry–based proteomics has emerged as the leading method for detection, quantification, and characterization of proteins. Nearly all proteomic workflows rely on proteomic databases to identify peptides and proteins, but these databases typically contain a generic set of proteins that lack variations unique to a given sample, precluding their detection. Fortunately, proteogenomics enables the detection of such proteomic variations and can be defined, broadly, as the use of nucleotide sequences to generate candidate protein sequences for mass spectrometry database searching. Proteogenomics is experiencing heightened significance due to two developments: (a) advances in DNA sequencing technologies that have made complete sequencing of human genomes and transcriptomes routine, and (b) the unveiling of the tremendous complexity of the human proteome as expressed at the levels of genes, cells, tissues, individuals, and populations. We review here the field of human proteogenomics, with an emphasis on its history, current implementations, the types of proteomic variations it reveals, and several important applications.
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