@inbook {doi:https://doi.org/10.1002/9783527833092.ch4,
	title = {Data Processing in Metabolomics Capillary Electrophoresis{\textendash}Mass Spectrometry},
	booktitle = {Capillary Electrophoresis-Mass Spectrometry for Proteomics and Metabolomics},
	year = {2022},
	pages = {121-145},
	publisher = {John Wiley \& Sons, Ltd},
	organization = {John Wiley \& Sons, Ltd},
	chapter = {4},
	abstract = {Summary Metabolomics data extraction may include peak deconvolution, alignment, and integration. The data extraction from CEMS spectra can usually be completed by a software designed for the extraction of liquid chromatography{\textendash}mass spectrometry (MS) spectra. The purpose of data preprocessing is to preliminarily adjust the obtained data to facilitate the following statistical analysis. Pre-acquisition normalization is relevant more to experimental setups than data processing, so this chapter discusses post-acquisition normalization, which mainly focuses on the data itself. Statistical analysis is the most important step in the processing of metabolomics data. The chapter also discusses some common statistical methods. One of the most significant differences between the data processing of proteomics and metabolomics is the identification of compounds. Metabolite identification usually starts from searching against databases. The Human Metabolome Database, METLIN database, and MassBank contain comprehensive information for many metabolites, including experimental and predicted MS/MS spectra obtained at multiple collision energies.},
	keywords = {CEMS spectra, data extraction, data preprocessing, data processing, metabolite identification, metabolomics, PROTEOMICS, statistical analysis},
	isbn = {9783527833092},
	doi = {https://doi.org/10.1002/9783527833092.ch4},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/9783527833092.ch4},
	author = {Tan, Jiahua and Huang, Zi-Ao and Morin, Gregg B. and Chen, David D. Y.}
}
@article {2663,
	title = {A Carboxy-Terminal Affinity Tag for the Purification and Mass Spectrometric Characterization of Integral Membrane Proteins},
	journal = {Journal of Proteome Research},
	volume = {8},
	number = {5},
	year = {2009},
	note = {ISI Document Delivery No.: 441BWTimes Cited: 3Cited Reference Count: 22Wong, Julie P. Reboul, Emmanuelle Molday, Robert S. Kast, Juergen},
	month = {May},
	pages = {2388-2396},
	type = {Article},
	abstract = {G-protein-coupled receptors (GPCRs) and other structurally and functionally related membrane proteins represent particularly attractive targets for drug discovery. Integral membrane proteins are often difficult to purify from native contexts, and lack of sufficient quantities hampers subsequent structural and functional proteomic studies. We describe here an optimized enrichment strategy involving a membrane protein-compatible 1D4 affinity tag that is derived from the carboxy-terminal nine amino residues of bovine rhodopsin, and its corresponding tag-specific, high-affinity monoclonal antibody. When two GPCRs as well as two related ATP binding cassette (ABC) transporters are expressed in their functional forms in human cell lines, we have shown that a single detergent and wash condition can be employed for the purification of all said membrane proteins. Subsequent in-gel digestion with trypsin and mass spectrometric peptide analysis resulted in high sequence coverage for the ABC transporters ABCA1-1D4 and ABCA4-1D4. In contrast, digestion by various enzymatic combinations was necessary to obtain the best sequence coverage for affinity-enriched GPCRs CXCR4-1D4 and CCR5-1D4 as compared against other entries in an annotated spectrum library. Furthermore, specific enzyme combinations were necessary to produce suitable peptides for deducing N-glycosylation sites on CXCR4. Our results demonstrate that the 1D4-tag enrichment strategy is a versatile tool for the characterization of integral membrane proteins that can be employed for functional proteomic studies.},
	keywords = {1D4 affinity tag, 2-DIMENSIONAL, annotated spectrum libraries, ATP binding cassette transporters, BINDING, ELECTROPHORESIS, EXPRESSION, G-protein-coupled, membrane protein enrichment, N-LINKED GLYCOSYLATION, PROTEOMICS, proteotypic peptides, RECEPTOR, RECEPTORS, RHODOPSIN, ROD OUTER SEGMENTS, SITES, SYNTHETIC PEPTIDES, Tandem mass spectrometry},
	isbn = {1535-3893},
	url = {<Go to ISI>://000265745300025},
	author = {Wong, J. P. and Reboul, E. and Molday, R. S. and Kast, J.}
}
@article {2648,
	title = {Implementation of a data repository-driven approach for targeted proteomics experiments by multiple reaction monitoring},
	journal = {Journal of Proteomics},
	volume = {72},
	number = {5},
	year = {2009},
	note = {ISI Document Delivery No.: 478RATimes Cited: 5Cited Reference Count: 30Walsh, Geraldine M. Lin, Shujun Evans, Daniel M. Khosrovi-Eghbal, Arash Beavis, Ronald C. Kast, Juergen},
	month = {Jul},
	pages = {838-852},
	type = {Article},
	abstract = {Multiple reaction monitoring (MRM), commonly employed for the mass spectrometric detection of small molecules, is rapidly gaining ground in proteomics. Its high sensitivity and specificity makes this targeted approach particularly useful when sample throughput or proteome coverage limits global studies. Existing tools to design MRM assays rely exclusively on theoretical predictions, or combine them with previous observations on the same type of sample. The additional mass spectrometric experimentation this requires can pose significant demands on time and material. To overcome these challenges, a new MRM worksheet was introduced into The Global Proteome Machine database (GPMDB) that provided all of the information needed to design MRM transitions based solely on archived observations made by other researchers in previous experiments. This required replacing the precursor ion intensity by the number of peptide observations, which proved to be an adequate substitute if peptides did not occur in multiple forms. While the absence of collision energy information proved largely inconsequential, successful prediction of unique transitions depended on the type of fragment ion involved. The design of MRM assays for iTRAQ-labeled tryptic peptides obtained from human platelet proteins demonstrated the usefulness of the MRM worksheet also for quantitative applications. This workflow, which relies exclusively on experimental observations stored in data repositories, therefore represents an attractive alternative for the prediction of MRM transitions prior to experimental validation and optimization. (C) 2008 Elsevier B.V. All rights reserved.},
	keywords = {ABSOLUTE, Data repository, HIGH-SENSITIVITY, LIBRARIES, Multiple reaction monitoring, PEPTIDES, PHOSPHORYLATION, PLASMA-PROTEINS, PLATELETS, PREDICTION, PROTEIN IDENTIFICATION, PROTEOMICS, QUANTIFICATION, SHOTGUN PROTEOMICS, Tandem mass spectrometry, TANDEM MASS-SPECTROMETRY, Targeted},
	isbn = {1874-3919},
	url = {<Go to ISI>://000268604400013},
	author = {Walsh, G. M. and Lin, S. and Evans, D. M. and Khosrovi-Eghbal, A. and Beavis, R. C. and Kast, J.}
}
@article {2290,
	title = {Mass spectrometric identification of formaldehyde-induced peptide modifications under in vivo protein cross-linking conditions},
	journal = {Analytica Chimica Acta},
	volume = {618},
	number = {2},
	year = {2008},
	note = {ISI Document Delivery No.: 317FDTimes Cited: 10Cited Reference Count: 19Toews, Judy Rogalski, Jason C. Clark, Thomas J. Kast, Juergen},
	month = {Jun},
	pages = {168-183},
	type = {Article},
	abstract = {Formaldehyde cross-linking of proteins is emerging as a novel approach to study protein-protein interactions in living cells. It has been shown to be compatible with standard techniques used in functional proteomics such as affinity-based protein enrichment, enzymatic digestion, and mass spectrometric protein identification. So far, the lack of knowledge on formaldehyde-induced protein modifications and suitable mass spectrometric methods for their targeted detection has impeded the identification of the different types of crosslinked peptides in these samples. In particular, it has remained unclear whether in vitro studies that identified a multitude of amino acid residues reacting with formaldehyde over the course of several days are suitable substitutes for the much shorter reaction times of 10-20 min used in cross-linking experiments in living cells. The current study on model peptides identifies amino-termini as well as lysine, tryptophan, and cysteine side chains, i.e. a small subset of those modified after several days, as the major reactive sites under such conditions, and suggests relative position in the peptide sequence as well as sequence microenvironment to be important factors that govern reactivity. Using MALDI-MS, mass increases of 12 Da on amino groups and 30 Da on cysteines were detected as the major reaction products, while peptide fragment ion analysis by tandem mass spectrometry was used to localize the actual modification sites on a peptide. Non-specific cross-linking was absent, and could only be detected with low yield at elevated peptide concentrations. The detailed knowledge on the constraints and products of the formaldehyde reaction with peptides after short incubation times presented in this study is expected to facilitate the targeted mass spectrometric analysis of proteins after in vivo formaldehyde cross-linking. (c) 2008 Elsevier B.V. All rights reserved.},
	keywords = {Chemical modification, COMPLEXES, FORMALDEHYDE, MAP, mass, NETWORK, peptide fragmentation, protein cross-linking, PROTEOMICS, PURIFICATION, REACTIVITY, SPECTROMETRY},
	isbn = {0003-2670},
	url = {<Go to ISI>://000257004400006},
	author = {Toews, J. and Rogalski, J. C. and Clark, T. J. and Kast, J.}
}
@article {2276,
	title = {Utility of formaldehyde cross-linking and mass spectrometry in the study of protein-protein interactions},
	journal = {Journal of Mass Spectrometry},
	volume = {43},
	number = {6},
	year = {2008},
	note = {ISI Document Delivery No.: 319PPTimes Cited: 22Cited Reference Count: 54Sutherland, Brent W. Toews, Judy Kast, Juergen},
	month = {Jun},
	pages = {699-715},
	type = {Article},
	abstract = {For decades, formaldehyde has been routinely used to cross-link proteins in cells, tissue, and in some instances, even entire organisms. Due to its small size, formaldehyde can readily permeate cell walls and membranes, resulting in efficient cross-linking, i.e. the formation of covalent bonds between proteins, DNA, and other reactive molecules. Indeed, formaldehyde cross-linking is an instrumental component of many mainstream analytical/cell biology techniques including chromatin immunoprecipitation (ChIP) of protein-DNA complexes found in nuclei; immunohistological analysis of protein expression and localization within cells, tissues, and organs; and mass spectrometry (MS)-compatible silver-staining methodologies used to visualize low abundance proteins in polyacrylamide gels. However, despite its exquisite suitability for use in the analysis of protein environments within cells, formaldehyde has yet to be commonly employed in the directed analysis of protein-protein interactions and cellular networks. The general purpose of this article is to discuss recent advancements in the use of formaldehyde cross-linking in combination with MS-based methodologies. Key advantages and limitations to the use of formaldehyde over other cross-linkers and technologies currently used to study protein-protein interactions are highlighted, and formaldehyde-based experimental approaches that are proving very promising in their ability to accurately and efficiently identify novel protein-protein and multiprotein interaction complexes are presented. Copyright (c) 2008 John Wiley \& Sons, Ltd.},
	keywords = {ANTIGEN-RETRIEVAL, CHROMATIN IMMUNOPRECIPITATION, COMPLEXES, CROSS-LINKING, FORMALDEHYDE, IDENTIFICATION, IMMUNOHISTOCHEMISTRY, INTERACTION NETWORKS, MASS SPECTROMETRY, PARAFFIN-EMBEDDED TISSUE, protein interactions, PROTEOMICS, review, SURFACE-TOPOLOGY, THROUGHPUT},
	isbn = {1076-5174},
	url = {<Go to ISI>://000257176400001},
	author = {Sutherland, B. W. and Toews, J. and Kast, J.}
}
@article {1238,
	title = {Statistical evaluation of electrospray tandem mass spectra for optimized peptide fragmentation},
	journal = {Journal of the American Society for Mass Spectrometry},
	volume = {16},
	number = {4},
	year = {2005},
	note = {ISI Document Delivery No.: 911RDTimes Cited: 6Cited Reference Count: 33},
	month = {Apr},
	pages = {505-514},
	type = {Article},
	abstract = {Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has become the method of choice for the analysis of complex peptide mixtures. It combines the separation power of nanoflow LC with highly specific sequence analysis, allowing automated peptide sequencing with high resolution and throughput. For peptide fragmentation, the current experimental setup uses predefined parameters based on the mass-to-charge ratio of the individual precursor. Suitable parameters are typically established by empirical evaluation of fragment spectra of individual peptides used as standards. As a result, nonoptimal fragment spectra are obtained if peptides show fragmentation behavior different from these standards, which often result in the loss of sequence-specific fragment ion information. Here we describe a statistical approach for the systematic evaluation of the quality of individual peptide fragment spectra based on the calculation of their arithmetic mean and standard deviation. The method utilizes the dependence of these parameters on the difference in electric potential across the collision cell to determine the value that results in maximum information content. We show that the method is applicable to fragment spectra generated from a variety of multiply-charged tryptic peptides, over a wide concentration range, and on different types of mass analyzers. We also show how this novel approach can be used to define optimized collision energy settings over a wide mass-to-charge range. (J Am Soc Mass Spectrom 2005,16,505-514) (c) 2005 American Society for Mass Spectrometry},
	keywords = {ALGORITHM, ASSISTED-LASER-DESORPTION/IONIZATION, COLLISION-INDUCED DISSOCIATION, DATABASE SEARCH, MIXTURES, PROTEIN IDENTIFICATION, PROTEOMICS, PROTONATED PEPTIDES, SPECTROMETRY},
	isbn = {1044-0305},
	url = {<Go to ISI>://000228021400010},
	author = {Rogalski, J. C. and Lin, M. S. and Sniatynski, M. J. and Taylor, R. J. and Youhnovski, N. and Przybylski, M. and Kast, J.}
}
